WorldWideScience

Sample records for brucei gambiense sleeping

  1. Mechanism of Trypanosoma brucei gambiense resistance to human serum

    DEFF Research Database (Denmark)

    Uzureau, Pierrick; Uzureau, Sophie; Lecordier, Laurence

    2013-01-01

    The African parasite Trypanosoma brucei gambiense accounts for 97% of human sleeping sickness cases. T. b. gambiense resists the specific human innate immunity acting against several other tsetse-fly-transmitted trypanosome species such as T. b. brucei, the causative agent of nagana disease......GP), which prevents APOL1 toxicity and induces stiffening of membranes upon interaction with lipids. Two additional features contribute to resistance to TLFs: reduction of sensitivity to APOL1 requiring cysteine protease activity, and TbHpHbR inactivation due to a L210S substitution. According...

  2. Characterization of Trypanosoma brucei gambiense stocks isolated ...

    African Journals Online (AJOL)

    Characterization of Trypanosoma brucei gambiense stocks isolated from humans by RAPD fingerprinting in Côte d'Ivoire: another evidence for multiple infections. ... a given isoenzyme profile (zymodeme), confirming that this fingerprinting method has a higher discriminative power (faster molecular clock) than isoenzymes.

  3. Nifurtimox-eflornithine combination therapy for second-stage Trypanosoma brucei gambiense sleeping sickness: a randomized clinical trial in Congo.

    Science.gov (United States)

    Priotto, Gerardo; Kasparian, Serena; Ngouama, Daniel; Ghorashian, Sara; Arnold, Ute; Ghabri, Salah; Karunakara, Unni

    2007-12-01

    Human African trypanosomiasis caused by Trypanosoma brucei gambiense is a fatal disease. Current treatment options for patients with second-stage disease are either highly toxic or impracticable in field conditions. We compared the efficacy and safety of the nifurtimox-eflornithine drug combination with the standard eflornithine regimen for the treatment of second-stage disease. A randomized, open-label, active-control, phase III clinical trial comparing 2 arms was conducted at the Sleeping Sickness Treatment Center, which was run by Medecins Sans Frontieres, in Nkayi, Bouenza Province, Republic of Congo. Patients were screened for inclusion and randomly assigned to receive eflornithine alone (400 mg/kg per day given intravenously every 6 h for 14 days) or eflornithine (400 mg/kg per day given intravenously every 12 h for 7 days) plus nifurtimox (15 mg/kg per day given orally every 8 h for 10 days). Patients were observed for 18 months. The study's outcomes were cure and adverse events attributable to treatment. A total of 103 patients with second-stage disease were enrolled. Cure rates were 94.1% for the eflornithine group and 96.2% for the nifurtimox-eflornithine group. Drug reactions were frequent in both arms, and severe reactions affected 25.5% of patients in the eflornithine group and 9.6% of those in the nifurtimox-eflornithine group, resulting in 2 and 1 treatment suspensions, respectively. There was 1 death in the eflornithine arm and no deaths in the nifurtimox-eflornithine arm. The nifurtimox-eflornithine combination appears to be a promising first-line therapy for second-stage sleeping sickness. If our findings are corroborated by ongoing findings from additional sites (a multicenter extension of this study), the new nifurtimox-eflornithine combination therapy will mark a major and multifaceted advance over current therapies.

  4. Detection of Trypanosoma brucei gambiense and T. b. rhodesiense ...

    African Journals Online (AJOL)

    Detection of Trypanosoma brucei gambiense and T. b. rhodesiense in Glossina fuscipes fuscipes ( Diptera: Glossinidae ) and Stomoxys flies using the polymerase chain reaction (PCR) technique in southern Sudan.

  5. Equivalence trial of melarsoprol and nifurtimox monotherapy and combination therapy for the treatment of second-stage Trypanosoma brucei gambiense sleeping sickness.

    Science.gov (United States)

    Bisser, Sylvie; N'Siesi, François-Xavier; Lejon, Veerle; Preux, Pierre-Marie; Van Nieuwenhove, Simon; Miaka Mia Bilenge, Constantin; Būscher, Philippe

    2007-02-01

    Treatment of second-stage sleeping sickness relies mainly on melarsoprol. Nifurtimox has been successfully used to cure melarsoprol-refractory sleeping sickness caused by Trypanosoma brucei gambiense infection. An open, randomized trial was conducted to test for equivalence between the standard melarsoprol regimen and 3 other regimens, as follows: standard melarsoprol therapy (3 series of 3.6 mg/kg/day intravenously [iv] for 3 days, with 7-day breaks between the series); 10-day incremental-dose melarsoprol therapy (0.6 mg/kg iv on day 1, 1.2 mg/kg iv on day 2, and 1.8 mg/kg iv on days 3-10); nifurtimox monotherapy for 14 days (5 mg/kg orally 3 times per day); and consecutive 10-day melarsoprol-nifurtimox combination therapy (0.6 mg/kg iv melarsoprol on day 1, 1.2 mg/kg iv melarsoprol on day 2, and 1.2 mg/kg/day iv melarsoprol combined with oral 7.5 mg/kg nifurtimox twice a day on days 3-10). Primary outcomes were relapse, severe adverse events, and death attributed to treatment. A total of 278 patients were randomized. The frequency of adverse events was similar between the standard melarsoprol regimen and the other regimens. Encephalopathic syndromes occurred in all groups and caused all deaths that were likely due to treatment. Relapses (n=48) were observed only with the 3 monotherapy regimens. A consecutive 10-day low-dose melarsoprol-nifurtimox combination is more effective than the standard melarsoprol regimen.

  6. Diagnosis of human trypanosomiasis, due to Trypanosoma brucei gambiense in central Africa, by the polymerase chain reaction

    OpenAIRE

    Penchenier, Laurent; Simo, G.; Grébaut, Pascal; Nkinin, S.; Laveissière, Claude; Herder, Stéphane

    2000-01-01

    During a mass screening of sleeping sickness conducted in 1998 and 1999, and involving 27,932 persons in Cameroon and the Central African Republic, we tested the polymerase chain reaction (PCR) on whole blood for the diagnosis of human African trypanosomiasis due to #Trypanosoma brucei gambiense$. The 1858 samples obtained were from 4 groups : 155 infected patients, 1432 serological suspects detected by the card agglutination test for trypanosomiasis (CATT), 222 negative controls living in th...

  7. Chimerization at the AQP2–AQP3 locus is the genetic basis of melarsoprol–pentamidine cross-resistance in clinical Trypanosoma brucei gambiense isolates

    Directory of Open Access Journals (Sweden)

    Fabrice E. Graf

    2015-08-01

    Full Text Available Aquaglyceroporin-2 is a known determinant of melarsoprol–pentamidine cross-resistance in Trypanosoma brucei brucei laboratory strains. Recently, chimerization at the AQP2–AQP3 tandem locus was described from melarsoprol–pentamidine cross-resistant Trypanosoma brucei gambiense isolates from sleeping sickness patients in the Democratic Republic of the Congo. Here, we demonstrate that reintroduction of wild-type AQP2 into one of these isolates fully restores drug susceptibility while expression of the chimeric AQP2/3 gene in aqp2–aqp3 null T. b. brucei does not. This proves that AQP2–AQP3 chimerization is the cause of melarsoprol–pentamidine cross-resistance in the T. b. gambiense isolates.

  8. Aparasitemic serological suspects in Trypanosoma brucei gambiense human African trypanosomiasis : a potential human reservoir of parasites ?

    OpenAIRE

    Koffi, Mathurin; Solano, Philippe; Denizot, M.; Courtin, D.; Garcia, André; Lejon, V.; Buscher, P.; Cuny, Gérard; Jamonneau, Vincent

    2006-01-01

    The serological and parasitological tests used for Trypanosoma brucei gambiense human African trypanosomiasis (HAT) diagnosis have low specificity and sensitivity, respectively, and in the field, control program teams are faced with subjects with positive serology but negative parasitology who remain untreated. The aim of this work was to explore, using PCR tool, the significance of these aparasitemic serological suspects. Since discordant PCR results have been observed earlier with different...

  9. Expression of Trypanosoma brucei gambiense Antigens in Leishmania tarentolae. Potential for Use in Rapid Serodiagnostic Tests (RDTs.

    Directory of Open Access Journals (Sweden)

    Barrie Rooney

    2015-12-01

    Full Text Available The development of rapid serodiagnostic tests for sleeping sickness and other diseases caused by kinetoplastids relies on the affordable production of parasite-specific recombinant antigens. Here, we describe the production of recombinant antigens from Trypanosoma brucei gambiense (T.b. gambiense in the related species Leishmania tarentolae (L. tarentolae, and compare their diagnostic sensitivity and specificity to native antigens currently used in diagnostic kits against a panel of human sera. A number of T.b. gambiense protein antigen candidates were chosen for recombinant expression in L. tarentolae based on current diagnostics in field use and recent findings on immunodiagnostic antigens found by proteomic profiling. In particular, the extracellular domains of invariant surface glycoprotein 65 (ISG65, variant surface glycoproteins VSG LiTat 1.3 and VSG LiTat 1.5 were fused with C-terminal histidine tags and expressed as soluble proteins in the medium of cultured, recombinant L. tarentolae. Using affinity chromatography, on average 10 mg/L of recombinant protein was purified from cultures and subsequently tested against a panel of sera from sleeping sickness patients from controls, i.e. persons without sleeping sickness living in HAT endemic countries. The evaluation on sera from 172 T.b. gambiense human African trypanosomiasis (HAT patients and from 119 controls showed very high diagnostic potential of the two recombinant VSG and the rISG65 fragments with areas under the curve between 0.97 and 0.98 compared to 0.98 and 0.99 with native VSG LiTat 1.3 and VSG LiTat 1.5 (statistically not different. Evaluation on sera from 78 T.b. rhodesiense HAT patients and from 100 controls showed an acceptable diagnostic potential of rISG65 with an area under the curve of 0.83. These results indicate that a combination of these recombinant antigens has the potential to be used in next generation rapid serodiagnostic tests. In addition, the L. tarentolae

  10. Detection of Trypanosoma brucei gambiense and T. b. rhodesiense ...

    African Journals Online (AJOL)

    GREGORY

    2010-09-20

    Sep 20, 2010 ... central Sudan. J. Anim. Vet. Adv. 4(11): 945-948. Baker JR (1974). Epidemiology of African sleeping sickness. In: Trypanosomiasis and Leishaniasis with Special Reference to Chagas. Disease. CIBA Foundation Symposium, pp. 29-50. Bloss JFE (1960). The history of sleeping sickness in sudan. Proc. R.

  11. Molecular Evidence of a Trypanosoma brucei gambiense Sylvatic Cycle in the Human African Trypanosomiasis Foci of Equatorial Guinea

    Directory of Open Access Journals (Sweden)

    Carlos eCordon-Obras

    2015-07-01

    Full Text Available Gambiense trypanosomiasis is considered an anthroponotic disease. Consequently, control programs are generally aimed at stopping transmission of Trypanosoma brucei gambiense (T. b. gambiense by detecting and treating human cases. However, the persistence of numerous foci despite efforts to eliminate this disease questions this strategy as unique tool to pursue the eradication. The role of animals as a reservoir of T. b. gambiense is still controversial, but could partly explain maintenance of the infection at hypo-endemic levels. In the present study, we evaluated the presence of T. b. gambiense in wild animals in Equatorial Guinea. The infection rate ranged from 0.8% in the insular focus of Luba to more than 12% in Mbini, a focus with a constant trickle of human cases. The parasite was detected in a wide range of animal species including four species never described previously as putative reservoirs. Our study comes to reinforce the hypothesis that animals may play a role in the persistence of T. b. gambiense transmission, being particularly relevant in low transmission settings. Under these conditions the integration of sustained vector control and medical interventions should be considered to achieve the elimination of Gambiense trypanosomiasis.

  12. Isolation and analysis of the genetic diversity of repertoires of VSG expression site containing telomeres from Trypanosoma brucei gambiense, T. b. brucei and T. equiperdum

    Directory of Open Access Journals (Sweden)

    Becker Marion

    2008-08-01

    Full Text Available Abstract Background African trypanosomes (including Trypanosoma brucei are unicellular parasites which multiply in the mammalian bloodstream. T. brucei has about twenty telomeric bloodstream form Variant Surface Glycoprotein (VSG expression sites (BESs, of which one is expressed at a time in a mutually exclusive fashion. BESs are polycistronic transcription units, containing a variety of families of expression site associated genes (ESAGs in addition to the telomeric VSG. These polymorphic ESAG families are thought to play a role in parasite-host adaptation, and it has been proposed that ESAG diversity might be related to host range. Analysis of the genetic diversity of these telomeric gene families has been confounded by the underrepresentation of telomeric sequences in standard libraries. We have previously developed a method to selectively isolate sets of trypanosome BES containing telomeres using Transformation associated recombination (TAR cloning in yeast. Results Here we describe the isolation of repertoires of BES containing telomeres from three trypanosome subspecies: Trypanosoma brucei gambiense DAL 972 (causative agent of West-African trypanosomiasis, T. b. brucei EATRO 2340 (a nonhuman infective strain and T. equiperdum STIB 818 (which causes a sexually transmitted disease in equines. We have sequenced and analysed the genetic diversity at four BES loci (BES promoter region, ESAG6, ESAG5 and ESAG2 from these three trypanosome BES repertoires. Conclusion With the exception of ESAG2, the BES sequence repertoires derived from T. b. gambiense are both less diverse than and nearly reciprocally monophyletic relative to those from T. b. brucei and T. equiperdum. Furthermore, although we find evidence for adaptive evolution in all three ESAG repertoires in T. b. brucei and T. equiperdum, only ESAG2 appears to be under diversifying selection in T. b. gambiense. This low level of variation in the T. b. gambiense BES sequence repertoires is

  13. Isolation and analysis of the genetic diversity of repertoires of VSG expression site containing telomeres from Trypanosoma brucei gambiense, T. b. brucei and T. equiperdum.

    Science.gov (United States)

    Young, Rosanna; Taylor, Jesse E; Kurioka, Ayako; Becker, Marion; Louis, Edward J; Rudenko, Gloria

    2008-08-12

    African trypanosomes (including Trypanosoma brucei) are unicellular parasites which multiply in the mammalian bloodstream. T. brucei has about twenty telomeric bloodstream form Variant Surface Glycoprotein (VSG) expression sites (BESs), of which one is expressed at a time in a mutually exclusive fashion. BESs are polycistronic transcription units, containing a variety of families of expression site associated genes (ESAGs) in addition to the telomeric VSG. These polymorphic ESAG families are thought to play a role in parasite-host adaptation, and it has been proposed that ESAG diversity might be related to host range. Analysis of the genetic diversity of these telomeric gene families has been confounded by the underrepresentation of telomeric sequences in standard libraries. We have previously developed a method to selectively isolate sets of trypanosome BES containing telomeres using Transformation associated recombination (TAR) cloning in yeast. Here we describe the isolation of repertoires of BES containing telomeres from three trypanosome subspecies: Trypanosoma brucei gambiense DAL 972 (causative agent of West-African trypanosomiasis), T. b. brucei EATRO 2340 (a nonhuman infective strain) and T. equiperdum STIB 818 (which causes a sexually transmitted disease in equines). We have sequenced and analysed the genetic diversity at four BES loci (BES promoter region, ESAG6, ESAG5 and ESAG2) from these three trypanosome BES repertoires. With the exception of ESAG2, the BES sequence repertoires derived from T. b. gambiense are both less diverse than and nearly reciprocally monophyletic relative to those from T. b. brucei and T. equiperdum. Furthermore, although we find evidence for adaptive evolution in all three ESAG repertoires in T. b. brucei and T. equiperdum, only ESAG2 appears to be under diversifying selection in T. b. gambiense. This low level of variation in the T. b. gambiense BES sequence repertoires is consistent both with the relatively narrow host range

  14. Loop Mediated Isothermal Amplification for Detection of Trypanosoma brucei gambiense in Urine and Saliva Samples in Nonhuman Primate Model

    Directory of Open Access Journals (Sweden)

    Maina Ngotho

    2015-01-01

    Full Text Available Human African trypanosomiasis (HAT is a vector-borne parasitic zoonotic disease. The disease caused by Trypanosoma brucei gambiense is the most prevalent in Africa. Early diagnosis is hampered by lack of sensitive diagnostic techniques. This study explored the potential of loop mediated isothermal amplification (LAMP and polymerase chain reaction (PCR in the detection of T. b. gambiense infection in a vervet monkey HAT model. Six vervet monkeys were experimentally infected with T. b. gambiense IL3253 and monitored for 180 days after infection. Parasitaemia was scored daily. Blood, cerebrospinal fluid (CSF, saliva, and urine samples were collected weekly. PCR and LAMP were performed on serum, CSF, saliva, and urine samples. The detection by LAMP was significantly higher than that of parasitological methods and PCR in all the samples. The performance of LAMP varied between the samples and was better in serum followed by saliva and then urine samples. In the saliva samples, LAMP had 100% detection between 21 and 77 dpi, whereas in urine the detection it was slightly lower, but there was over 80% detection between 28 and 91 dpi. However, LAMP could not detect trypanosomes in either saliva or urine after 140 and 126 dpi, respectively. The findings of this study emphasize the importance of LAMP in diagnosis of HAT using saliva and urine samples.

  15. Loop Mediated Isothermal Amplification for Detection of Trypanosoma brucei gambiense in Urine and Saliva Samples in Nonhuman Primate Model.

    Science.gov (United States)

    Ngotho, Maina; Kagira, John Maina; Gachie, Beatrice Muthoni; Karanja, Simon Muturi; Waema, Maxwell Wambua; Maranga, Dawn Nyawira; Maina, Naomi Wangari

    2015-01-01

    Human African trypanosomiasis (HAT) is a vector-borne parasitic zoonotic disease. The disease caused by Trypanosoma brucei gambiense is the most prevalent in Africa. Early diagnosis is hampered by lack of sensitive diagnostic techniques. This study explored the potential of loop mediated isothermal amplification (LAMP) and polymerase chain reaction (PCR) in the detection of T. b. gambiense infection in a vervet monkey HAT model. Six vervet monkeys were experimentally infected with T. b. gambiense IL3253 and monitored for 180 days after infection. Parasitaemia was scored daily. Blood, cerebrospinal fluid (CSF), saliva, and urine samples were collected weekly. PCR and LAMP were performed on serum, CSF, saliva, and urine samples. The detection by LAMP was significantly higher than that of parasitological methods and PCR in all the samples. The performance of LAMP varied between the samples and was better in serum followed by saliva and then urine samples. In the saliva samples, LAMP had 100% detection between 21 and 77 dpi, whereas in urine the detection it was slightly lower, but there was over 80% detection between 28 and 91 dpi. However, LAMP could not detect trypanosomes in either saliva or urine after 140 and 126 dpi, respectively. The findings of this study emphasize the importance of LAMP in diagnosis of HAT using saliva and urine samples.

  16. Aquaporin 2 mutations in Trypanosoma brucei gambiense field isolates correlate with decreased susceptibility to pentamidine and melarsoprol.

    Directory of Open Access Journals (Sweden)

    Fabrice E Graf

    Full Text Available The predominant mechanism of drug resistance in African trypanosomes is decreased drug uptake due to loss-of-function mutations in the genes for the transporters that mediate drug import. The role of transporters as determinants of drug susceptibility is well documented from laboratory-selected Trypanosoma brucei mutants. But clinical isolates, especially of T. b. gambiense, are less amenable to experimental investigation since they do not readily grow in culture without prior adaptation. Here we analyze a selected panel of 16 T. brucei ssp. field isolates that (i have been adapted to axenic in vitro cultivation and (ii mostly stem from treatment-refractory cases. For each isolate, we quantify the sensitivity to melarsoprol, pentamidine, and diminazene, and sequence the genomic loci of the transporter genes TbAT1 and TbAQP2. The former encodes the well-characterized aminopurine permease P2 which transports several trypanocides including melarsoprol, pentamidine, and diminazene. We find that diminazene-resistant field isolates of T. b. brucei and T. b. rhodesiense carry the same set of point mutations in TbAT1 that was previously described from lab mutants. Aquaglyceroporin 2 has only recently been identified as a second transporter involved in melarsoprol/pentamidine cross-resistance. Here we describe two different kinds of TbAQP2 mutations found in T. b. gambiense field isolates: simple loss of TbAQP2, or loss of wild-type TbAQP2 allele combined with the formation of a novel type of TbAQP2/3 chimera. The identified mutant T. b. gambiense are 40- to 50-fold less sensitive to pentamidine and 3- to 5-times less sensitive to melarsoprol than the reference isolates. We thus demonstrate for the first time that rearrangements of the TbAQP2/TbAQP3 locus accompanied by TbAQP2 gene loss also occur in the field, and that the T. b. gambiense carrying such mutations correlate with a significantly reduced susceptibility to pentamidine and melarsoprol.

  17. In vitro investigation of Brazilian Cerrado plant extract activity against Plasmodium falciparum, Trypanosoma cruzi and T. brucei gambiense.

    Science.gov (United States)

    Charneau, Sébastien; de Mesquita, Mariana Laundry; Bastos, Izabela Marques Dourado; Santana, Jaime Martins; de Paula, José Elias; Grellier, Philippe; Espindola, Laila Salmen

    2016-06-01

    The threatened Brazilian Cerrado biome is an important biodiversity hotspot but still few explored that constitutes a potential reservoir of molecules to treat infectious diseases. We selected eight Cerrado plant species for screening against the erythrocytic stages of Plasmodium falciparum, human intracellular stages of Trypanosoma cruzi and bloodstream forms of T. brucei gambiense, and for their cytotoxicity upon the rat L6-myoblast cell line. Bioassays were performed with 37 hexane, ethyl acetate and ethanol extracts prepared from different plant organs. Activities against parasites were observed for 24 extracts: 9 with anti-P. falciparum, 4 with anti-T. cruzi and 11 with anti-T. brucei gambiense activities. High anti-protozoal activity (IC50 values < 10 μg/mL) without obvious cytotoxicity to L6 cells was observed for eight extracts from plants: Connarus suberosus, Blepharocalyx salicifolius, Psidium laruotteanum and Myrsine guianensis. Overall, studies of plant extracts will contribute to increase the biodiversity knowledge essential for Cerrado conservation and sustainable development.

  18. Trypanosoma brucei gambiense Infections in Mice Lead to Tropism to the Reproductive Organs, and Horizontal and Vertical Transmission.

    Directory of Open Access Journals (Sweden)

    Nicolas Biteau

    2016-01-01

    Full Text Available Trypanosoma brucei gambiense, transmitted by the tsetse fly, is the main causative agent of Human African trypanosomosis in West Africa and poses a significant health risk to 70 million people. Disease progression varies depending on host immunity, but usually begins with a haemo-lymphatic phase, followed by parasite invasion of the central nervous system. In the current study, the tropism of T. b. gambiense 1135, causing a low level chronic 'silent' infection, was monitored in a murine model using bioluminescence imaging and PCR. A tropism to the reproductive organs, in addition to the central nervous system, after 12-18 months of infection was observed. Bioluminescent analysis of healthy females crossed with infected males showed that 50%, 62.5% and 37.5% of the female mice were subsequently positive for parasites in their ovaries, uteri and brain respectively. Although PCR confirmed the presence of parasites in the uterus of one of these mice, the blood of all mice was negative by PCR and LAMP. Subsequently, bioluminescent imaging of the offspring of infected female mice crossed with healthy males indicated parasites were present in the reproductive organs of both male (80% and female (60% offspring. These findings imply that transmission of T. b. gambiense 1135 occurs horizontally, most probably via sexual contact, and vertically in a murine model, which raises the possibility of a similar transmission in humans. This has wide reaching implications. Firstly, the observations made in this study are likely to be valid for wild animals acting as a reservoir for T. b. gambiense. Also, the reproductive organs may act as a refuge for parasites during drug treatment in a similar manner to the central nervous system. This could leave patients at risk of a relapse, ultimately allowing them to act as a reservoir for subsequent transmission by tsetse and possibly, horizontally and vertically.

  19. Cultivation in a semi-defined medium of animal infective forms of Trypanosoma brucei, T. equiperdum, T. evansi, T. rhodesiense and T. gambiense.

    Science.gov (United States)

    Baltz, T; Baltz, D; Giroud, C; Crockett, J

    1985-05-01

    A semi-defined medium for the cultivation of bloodstream forms of the African trypanosome brucei subgroup was developed. Out of 14 different strains tested, 10 could be cultured including Trypanosoma brucei, T. equiperdum, T. evansi, T. rhodesiense and T. gambiense. The presence of a reducing agent (2-mercaptoethanol or thioglycerol) was found to be essential for growth. The standard medium consisted of Hepes buffered minimum essential medium with Earle's salts supplemented with 0.2 mM 2-mercaptoethanol, 2 mM pyruvate and 10% inactivated serum either from rabbit (T. brucei, T. equiperdum, T. evansi and T. rhodesiense) or human (T. gambiense). Although a general medium could be defined for the long-term maintenance of trypanosome cultures, the initiation to culture nevertheless required particular conditions for the different strains. The cultured trypanosomes had all the characteristics of the in vivo bloodstream forms including: morphology, infectivity, antigenic variation and glucose metabolism.

  20. Trypanosoma brucei gambiense group 1 is distinguished by a unique amino acid substitution in the HpHb receptor implicated in human serum resistance.

    Directory of Open Access Journals (Sweden)

    Rebecca E Symula

    Full Text Available Trypanosoma brucei rhodesiense (Tbr and T. b. gambiense (Tbg, causative agents of Human African Trypanosomiasis (sleeping sickness in Africa, have evolved alternative mechanisms of resisting the activity of trypanosome lytic factors (TLFs, components of innate immunity in human serum that protect against infection by other African trypanosomes. In Tbr, lytic activity is suppressed by the Tbr-specific serum-resistance associated (SRA protein. The mechanism in Tbg is less well understood but has been hypothesized to involve altered activity and expression of haptoglobin haemoglobin receptor (HpHbR. HpHbR has been shown to facilitate internalization of TLF-1 in T.b. brucei (Tbb, a member of the T. brucei species complex that is susceptible to human serum. By evaluating the genetic variability of HpHbR in a comprehensive geographical and taxonomic context, we show that a single substitution that replaces leucine with serine at position 210 is conserved in the most widespread form of Tbg (Tbg group 1 and not found in related taxa, which are either human serum susceptible (Tbb or known to resist lysis via an alternative mechanism (Tbr and Tbg group 2. We hypothesize that this single substitution contributes to reduced uptake of TLF and thus may play a key role in conferring serum resistance to Tbg group 1. In contrast, similarity in HpHbR sequence among isolates of Tbg group 2 and Tbb/Tbr provides further evidence that human serum resistance in Tbg group 2 is likely independent of HpHbR function.

  1. Digital gene expression analysis of two life cycle stages of the human-infective parasite, Trypanosoma brucei gambiense reveals differentially expressed clusters of co-regulated genes

    Directory of Open Access Journals (Sweden)

    Wildridge David

    2010-02-01

    Full Text Available Abstract Background The evolutionarily ancient parasite, Trypanosoma brucei, is unusual in that the majority of its genes are regulated post-transcriptionally, leading to the suggestion that transcript abundance of most genes does not vary significantly between different life cycle stages despite the fact that the parasite undergoes substantial cellular remodelling and metabolic changes throughout its complex life cycle. To investigate this in the clinically relevant sub-species, Trypanosoma brucei gambiense, which is the causative agent of the fatal human disease African sleeping sickness, we have compared the transcriptome of two different life cycle stages, the potentially human-infective bloodstream forms with the non-human-infective procyclic stage using digital gene expression (DGE analysis. Results Over eleven million unique tags were generated, producing expression data for 7360 genes, covering 81% of the genes in the genome. Compared to microarray analysis of the related T. b. brucei parasite, approximately 10 times more genes with a 2.5-fold change in expression levels were detected. The transcriptome analysis revealed the existence of several differentially expressed gene clusters within the genome, indicating that contiguous genes, presumably from the same polycistronic unit, are co-regulated either at the level of transcription or transcript stability. Conclusions DGE analysis is extremely sensitive for detecting gene expression differences, revealing firstly that a far greater number of genes are stage-regulated than had previously been identified and secondly and more importantly, this analysis has revealed the existence of several differentially expressed clusters of genes present on what appears to be the same polycistronic units, a phenomenon which had not previously been observed in microarray studies. These differentially regulated clusters of genes are in addition to the previously identified RNA polymerase I polycistronic

  2. A single amino acid substitution in the group 1 Trypanosoma brucei gambiense haptoglobin-hemoglobin receptor abolishes TLF-1 binding.

    Directory of Open Access Journals (Sweden)

    E DeJesus

    Full Text Available Critical to human innate immunity against African trypanosomes is a minor subclass of human high-density lipoproteins, termed Trypanosome Lytic Factor-1 (TLF-1. This primate-specific molecule binds to a haptoglobin-hemoglobin receptor (HpHbR on the surface of susceptible trypanosomes, initiating a lytic pathway. Group 1 Trypanosoma brucei gambiense causes human African Trypanosomiasis (HAT, escaping TLF-1 killing due to reduced uptake. Previously, we found that group 1 T. b. gambiense HpHbR (TbgHpHbR mRNA levels were greatly reduced and the gene contained substitutions within the open reading frame. Here we show that a single, highly conserved amino acid in the TbgHpHbR ablates high affinity TLF-1 binding and subsequent endocytosis, thus evading TLF-1 killing. In addition, we show that over-expression of TbgHpHbR failed to rescue TLF-1 susceptibility. These findings suggest that the single substitution present in the TbgHpHbR directly contributes to the reduced uptake and resistance to TLF-1 seen in these important human pathogens.

  3. Contemporary and emerging strategies for eliminating human African trypanosomiasis due to Trypanosoma brucei gambiense: review.

    Science.gov (United States)

    Steinmann, Peter; Stone, Christopher M; Sutherland, C Simone; Tanner, Marcel; Tediosi, Fabrizio

    2015-06-01

    To review current and emerging tools for Gambiense HAT control and elimination, and propose strategies that integrate these tools with epidemiological evidence. We reviewed the scientific literature to identify contemporary and emerging tools and strategies for controlling and eliminating Gambiense HAT. Through an iterative process involving key stakeholders, we then developed comprehensive scenarios leading to elimination, considering both established and new tools for diagnosis, case treatment and vector control. Core components of all scenarios include detecting and treating cases with established or emerging techniques. Relatively more intensive scenarios incorporate vector control. New tools considered include tiny targets for tsetse fly control, use of rapid diagnostic tests and oral treatment with fexinidazole or oxaboroles. Scenarios consider the time when critical new tools are expected to become ready for deployment by national control programmes. Based on a review of the latest epidemiological data, we estimate the various interventions to cover 1,380,600 km(2) and 56,986,000 people. A number of new tools will fill critical gaps in the current armamentarium for diagnosing and treating Gambiense HAT. Deploying these tools in endemic areas will facilitate the comprehensive and sustainable control of the disease considerably and contribute to the ultimate goal of elimination. © 2015 John Wiley & Sons Ltd.

  4. First evidence that parasite infecting apparent aparasitemic serological suspects in human African trypanosomiasis are Trypanosoma brucei gambiense and are similar to those found in patients.

    Science.gov (United States)

    Kaboré, Jacques; Koffi, Mathurin; Bucheton, Bruno; MacLeod, Annette; Duffy, Craig; Ilboudo, Hamidou; Camara, Mamadou; De Meeûs, Thierry; Belem, Adrien Marie Gaston; Jamonneau, Vincent

    2011-08-01

    Thanks to its sensitivity and its ease of use in the field, the card agglutination test for trypanosomiasis (CATT) is widely used for serological screening of Trypanosoma brucei gambiense human African trypanosomiasis (HAT). Positive subjects are then examined by microscopy to confirm the disease. However, the CATT exhibits false-positive results raising the question of whether CATT-positive subjects who are not confirmed by microscopic detection of trypanosomes (SERO) are truly exposed to T.b. gambiense infection. For this purpose, we applied microsatellite genotyping on DNA extracted from blood of both HAT confirmed patients and SERO subjects in Guinea and Côte d'Ivoire since microsatellite genotyping has proved useful for the study of T.b. gambiense genetic diversity. Problems of amplification failures raise the question of the sensitivity of microsatellite markers when applied on biological samples especially from SERO subjects for who low blood parasitaemia are suspected. Nevertheless, we have shown that the trypanosomes from SERO individuals that have been genotyped belong to T.b. gambiense group 1 and were identical to those found in HAT patients. These results constitute the first evidences that at least some SERO are indeed infected by T.b. gambiense group 1 and that they may constitute a human reservoir of parasite in HAT foci. Whether these individuals should undergo treatment remains an open question as long as their role in HAT transmission is unknown. Our results strongly recommend the follow-up of such subjects to improve control strategies. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. The study of trypanosome species circulating in domestic animals in two human African trypanosomiasis foci of Côte d'Ivoire identifies pigs and cattle as potential reservoirs of Trypanosoma brucei gambiense.

    Science.gov (United States)

    N'Djetchi, Martial Kassi; Ilboudo, Hamidou; Koffi, Mathurin; Kaboré, Jacques; Kaboré, Justin Windingoudi; Kaba, Dramane; Courtin, Fabrice; Coulibaly, Bamoro; Fauret, Pierre; Kouakou, Lingué; Ravel, Sophie; Deborggraeve, Stijn; Solano, Philippe; De Meeûs, Thierry; Bucheton, Bruno; Jamonneau, Vincent

    2017-10-01

    Important control efforts have led to a significant reduction of the prevalence of human African trypanosomiasis (HAT) in Côte d'Ivoire, but the disease is still present in several foci. The existence of an animal reservoir of Trypanosoma brucei gambiense may explain disease persistence in these foci where animal breeding is an important source of income but where the prevalence of animal African trypanosomiasis (AAT) is unknown. The aim of this study was to identify the trypanosome species circulating in domestic animals in both Bonon and Sinfra HAT endemic foci. 552 domestic animals (goats, pigs, cattle and sheep) were included. Blood samples were tested for trypanosomes by microscopic observation, species-specific PCR for T. brucei sl, T. congolense, T. vivax and subspecies-specific PCR for T. b. gambiense and T. b. gambiense immune trypanolysis (TL). Infection rates varied significantly between animal species and were by far the highest in pigs (30%). T. brucei s.l was the most prevalent trypanosome species (13.7%) followed by T. congolense. No T. b. gambiense was identified by PCR while high TL positivity rates were observed using T. b. gambiense specific variants (up to 27.6% for pigs in the Bonon focus). This study shows that domestic animals are highly infected by trypanosomes in the studied foci. This was particularly true for pigs, possibly due to a higher exposure of these animals to tsetse flies. Whereas T. brucei s.l. was the most prevalent species, discordant results were obtained between PCR and TL regarding T. b. gambiense identification. It is therefore crucial to develop better tools to study the epidemiological role of potential animal reservoir for T. b. gambiense. Our study illustrates the importance of "one health" approaches to reach HAT elimination and contribute to AAT control in the studied foci.

  6. In-hospital safety in field conditions of nifurtimox eflornithine combination therapy (NECT) for T. b. gambiense sleeping sickness.

    Science.gov (United States)

    Schmid, Caecilia; Kuemmerle, Andrea; Blum, Johannes; Ghabri, Salah; Kande, Victor; Mutombo, Wilfried; Ilunga, Medard; Lumpungu, Ismael; Mutanda, Sylvain; Nganzobo, Pathou; Tete, Digas; Mubwa, Nono; Kisala, Mays; Blesson, Severine; Mordt, Olaf Valverde

    2012-01-01

    Trypanosoma brucei (T.b.) gambiense Human African trypanosomiasis (HAT; sleeping sickness) is a fatal disease. Until 2009, available treatments for 2(nd) stage HAT were complicated to use, expensive (eflornithine monotherapy), or toxic, and insufficiently effective in certain areas (melarsoprol). Recently, nifurtimox-eflornithine combination therapy (NECT) demonstrated good safety and efficacy in a randomised controlled trial (RCT) and was added to the World Health Organisation (WHO) essential medicines list (EML). Documentation of its safety profile in field conditions will support its wider use. In a multicentre, open label, single arm, phase IIIb study of the use of NECT for 2(nd) stage T.b. gambiense HAT, all patients admitted to the trial centres who fulfilled inclusion criteria were treated with NECT. The primary outcome was the proportion of patients discharged alive from hospital. Safety was further assessed based on treatment emergent adverse events (AEs) occurring during hospitalisation. 629 patients were treated in six HAT treatment facilities in the Democratic Republic of the Congo (DRC), including 100 children under 12, 14 pregnant and 33 breastfeeding women. The proportion of patients discharged alive after treatment completion was 98.4% (619/629; 95%CI [97.1%; 99.1%]). Of the 10 patients who died during hospitalisation, 8 presented in a bad or very bad health condition at baseline; one death was assessed as unlikely related to treatment. No major or unexpected safety concerns arose in any patient group. Most common AEs were gastro-intestinal (61%), general (46%), nervous system (mostly central; 34%) and metabolic disorders (26%). The overall safety profile was similar to previously published findings. In field conditions and in a wider population, including children, NECT displayed a similar tolerability profile to that described in more stringent clinical trial conditions. The in-hospital safety was comparable to published results, and long term

  7. Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: a pivotal multicentre, randomised, non-inferiority trial.

    Science.gov (United States)

    Mesu, Victor Kande Betu Ku; Kalonji, Wilfried Mutombo; Bardonneau, Clélia; Mordt, Olaf Valverde; Blesson, Séverine; Simon, François; Delhomme, Sophie; Bernhard, Sonja; Kuziena, Willy; Lubaki, Jean-Pierre Fina; Vuvu, Steven Lumeya; Ngima, Pathou Nganzobo; Mbembo, Hélène Mahenzi; Ilunga, Médard; Bonama, Augustin Kasongo; Heradi, Josué Amici; Solomo, Jean Louis Lumaliza; Mandula, Guylain; Badibabi, Lewis Kaninda; Dama, Francis Regongbenga; Lukula, Papy Kavunga; Tete, Digas Ngolo; Lumbala, Crispin; Scherrer, Bruno; Strub-Wourgaft, Nathalie; Tarral, Antoine

    2017-11-04

    Few therapeutic options are available to treat the late-stage of human African trypanosomiasis, a neglected tropical disease, caused by Trypanosoma brucei gambiense (g-HAT). The firstline treatment is a combination therapy of oral nifurtimox and intravenous eflornithine that needs to be administered in a hospital setting by trained personnel, which is not optimal given that patients often live in remote areas with few health resources. Therefore, we aimed to assess the safety and efficacy of an oral regimen of fexinidazole (a 2-substituted 5-nitroimidazole with proven trypanocidal activity) versus nifurtimox eflornithine combination therapy in patients with late-stage g-HAT. In this randomised, phase 2/3, open-label, non-inferiority trial, we recruited patients aged 15 years and older with late-stage g-HAT from g-HAT treatment centres in the Democratic Republic of the Congo (n=9) and the Central African Republic (n=1). Patients were randomly assigned (2:1) to receive either fexinidazole or nifurtimox eflornithine combination therapy according to a predefined randomisation list (block size six). The funder, data management personnel, and study statisticians were masked to treatment. Oral fexinidazole was given once a day (days 1-4: 1800 mg, days 5-10: 1200 mg). Oral nifurtimox was given three times a day (days 1-10: 15 mg/kg per day) with eflornithine twice a day as 2 h infusions (days 1-7: 400 mg/kg per day). The primary endpoint was success at 18 months (ie, deemed as patients being alive, having no evidence of trypanosomes in any body fluid, not requiring rescue medication, and having a cerebrospinal fluid white blood cell count ≤20 cells per μL). Safety was assessed through routine monitoring. Primary efficacy analysis was done in the modified intention-to-treat population and safety analyses in the intention-to-treat population. The acceptable margin for the difference in success rates was defined as 13%. This study has been completed and is registered with

  8. Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial.

    Science.gov (United States)

    Priotto, Gerardo; Kasparian, Serena; Mutombo, Wilfried; Ngouama, Daniel; Ghorashian, Sara; Arnold, Ute; Ghabri, Salah; Baudin, Elisabeth; Buard, Vincent; Kazadi-Kyanza, Serge; Ilunga, Médard; Mutangala, Willy; Pohlig, Gabriele; Schmid, Caecilia; Karunakara, Unni; Torreele, Els; Kande, Victor

    2009-07-04

    Human African trypanosomiasis (HAT; sleeping sickness) caused by Trypanosoma brucei gambiense is a fatal disease. Current treatment options for patients with second-stage disease are toxic, ineffective, or impractical. We assessed the efficacy and safety of nifurtimox-eflornithine combination therapy (NECT) for second-stage disease compared with the standard eflornithine regimen. A multicentre, randomised, open-label, active control, phase III, non-inferiority trial was done at four HAT treatment centres in the Republic of the Congo and the Democratic Republic of the Congo. Patients aged 15 years or older with confirmed second-stage T b gambiense infection were randomly assigned by computer-generated randomisation sequence to receive intravenous eflornithine (400 mg/kg per day, every 6 h; n=144) for 14 days or intravenous eflornithine (400 mg/kg per day, every 12 h) for 7 days with oral nifurtimox (15 mg/kg per day, every 8 h) for 10 days (NECT; n=143). The primary endpoint was cure (defined as absence of trypanosomes in body fluids and a leucocyte count

  9. In-hospital safety in field conditions of nifurtimox eflornithine combination therapy (NECT for T. b. gambiense sleeping sickness.

    Directory of Open Access Journals (Sweden)

    Caecilia Schmid

    Full Text Available Trypanosoma brucei (T.b. gambiense Human African trypanosomiasis (HAT; sleeping sickness is a fatal disease. Until 2009, available treatments for 2(nd stage HAT were complicated to use, expensive (eflornithine monotherapy, or toxic, and insufficiently effective in certain areas (melarsoprol. Recently, nifurtimox-eflornithine combination therapy (NECT demonstrated good safety and efficacy in a randomised controlled trial (RCT and was added to the World Health Organisation (WHO essential medicines list (EML. Documentation of its safety profile in field conditions will support its wider use.In a multicentre, open label, single arm, phase IIIb study of the use of NECT for 2(nd stage T.b. gambiense HAT, all patients admitted to the trial centres who fulfilled inclusion criteria were treated with NECT. The primary outcome was the proportion of patients discharged alive from hospital. Safety was further assessed based on treatment emergent adverse events (AEs occurring during hospitalisation.629 patients were treated in six HAT treatment facilities in the Democratic Republic of the Congo (DRC, including 100 children under 12, 14 pregnant and 33 breastfeeding women. The proportion of patients discharged alive after treatment completion was 98.4% (619/629; 95%CI [97.1%; 99.1%]. Of the 10 patients who died during hospitalisation, 8 presented in a bad or very bad health condition at baseline; one death was assessed as unlikely related to treatment. No major or unexpected safety concerns arose in any patient group. Most common AEs were gastro-intestinal (61%, general (46%, nervous system (mostly central; 34% and metabolic disorders (26%. The overall safety profile was similar to previously published findings.In field conditions and in a wider population, including children, NECT displayed a similar tolerability profile to that described in more stringent clinical trial conditions. The in-hospital safety was comparable to published results, and long term

  10. Accuracy of individual rapid tests for serodiagnosis of gambiense sleeping sickness in West Africa.

    Directory of Open Access Journals (Sweden)

    Vincent Jamonneau

    2015-02-01

    Full Text Available Individual rapid tests for serodiagnosis (RDT of human African trypanosomiasis (HAT are particularly suited for passive screening and surveillance. However, so far, no large scale evaluation of RDTs has been performed for diagnosis of Trypanosoma brucei gambiense HAT in West Africa. The objective of this study was to assess the diagnostic accuracy of 2 commercial HAT-RDTs on stored plasma samples from West Africa.SD Bioline HAT and HAT Sero-K-Set were performed on 722 plasma samples originating from Guinea and Côte d'Ivoire, including 231 parasitologically confirmed HAT patients, 257 healthy controls, and 234 unconfirmed individuals whose blood tested antibody positive in the card agglutination test but negative by parasitological tests. Immune trypanolysis was performed as a reference test for trypanosome specific antibody presence. Sensitivities in HAT patients were respectively 99.6% for SD Bioline HAT, and 99.1% for HAT Sero-K-Set, specificities in healthy controls were respectively 87.9% and 88.3%. Considering combined positivity in both RDTs, increased the specificity significantly (p ≤ 0.0003 to 93.4%, while 98.7% sensitivity was maintained. Specificities in controls were 98.7-99.6% for the combination of one or two RDTs with trypanolysis, maintaining a sensitivity of at least 98.1%.The observed specificity of the single RDTs was relatively low. Serial application of SD Bioline HAT and HAT Sero-K-Set might offer superior specificity compared to a single RDT, maintaining high sensitivity. The combination of one or two RDTs with trypanolysis seems promising for HAT surveillance.

  11. The Phosphoproteome of Bloodstream Form Trypanosoma brucei, Causative Agent of African Sleeping Sickness

    OpenAIRE

    Nett, Isabelle R. E.; Martin, David M. A.; Miranda-Saavedra, Diego; Lamont, Douglas; Barber, Jonathan D.; Mehlert, Angela; Ferguson, Michael A. J.

    2009-01-01

    The protozoan parasite Trypanosoma brucei is the causative agent of human African sleeping sickness and related animal diseases, and it has over 170 predicted protein kinases. Protein phosphorylation is a key regulatory mechanism for cellular function that, thus far, has been studied in T.brucei principally through putative kinase mRNA knockdown and observation of the resulting phenotype. However, despite the relatively large kinome of this organism and the demonstrated essentiality of severa...

  12. The phosphoproteome of bloodstream form Trypanosoma brucei, causative agent of African sleeping sickness.

    Science.gov (United States)

    Nett, Isabelle R E; Martin, David M A; Miranda-Saavedra, Diego; Lamont, Douglas; Barber, Jonathan D; Mehlert, Angela; Ferguson, Michael A J

    2009-07-01

    The protozoan parasite Trypanosoma brucei is the causative agent of human African sleeping sickness and related animal diseases, and it has over 170 predicted protein kinases. Protein phosphorylation is a key regulatory mechanism for cellular function that, thus far, has been studied in T.brucei principally through putative kinase mRNA knockdown and observation of the resulting phenotype. However, despite the relatively large kinome of this organism and the demonstrated essentiality of several T. brucei kinases, very few specific phosphorylation sites have been determined in this organism. Using a gel-free, phosphopeptide enrichment-based proteomics approach we performed the first large scale phosphorylation site analyses for T.brucei. Serine, threonine, and tyrosine phosphorylation sites were determined for a cytosolic protein fraction of the bloodstream form of the parasite, resulting in the identification of 491 phosphoproteins based on the identification of 852 unique phosphopeptides and 1204 phosphorylation sites. The phosphoproteins detected in this study are predicted from their genome annotations to participate in a wide variety of biological processes, including signal transduction, processing of DNA and RNA, protein synthesis, and degradation and to a minor extent in metabolic pathways. The analysis of phosphopeptides and phosphorylation sites was facilitated by in-house developed software, and this automated approach was validated by manual annotation of spectra of the kinase subset of proteins. Analysis of the cytosolic bloodstream form T. brucei kinome revealed the presence of 44 phosphorylated protein kinases in our data set that could be classified into the major eukaryotic protein kinase groups by applying a multilevel hidden Markov model library of the kinase catalytic domain. Identification of the kinase phosphorylation sites showed conserved phosphorylation sequence motifs in several kinase activation segments, supporting the view that

  13. Trypanosoma brucei CYP51: Essentiality and Targeting Therapy in an Experimental Model.

    Directory of Open Access Journals (Sweden)

    Frédéric-Antoine Dauchy

    2016-11-01

    Full Text Available Trypanosoma brucei gambiense is the main causative agent of Human African Trypanosomiasis (HAT, also known as sleeping sickness. Because of limited alternatives and treatment toxicities, new therapeutic options are urgently needed for patients with HAT. Sterol 14alpha-demethylase (CYP51 is a potential drug target but its essentiality has not been determined in T. brucei. We used a tetracycline-inducible RNAi system to assess the essentiality of CYP51 in T. brucei bloodstream form (BSF cells and we evaluated the effect of posaconazole, a well-tolerated triazole drug, within a panel of virulent strains in vitro and in a murine model. Expression of CYP51 in several T. brucei cell lines was demonstrated by western blot and its essentiality was demonstrated by RNA interference (CYP51RNAi in vitro. Following reduction of TbCYP51 expression by RNAi, cell growth was reduced and eventually stopped compared to WT or non-induced cells, showing the requirement of CYP51 in T. brucei. These phenotypes were rescued by addition of ergosterol. Additionally, CYP51RNAi induction caused morphological defects with multiflagellated cells (p<0.05, suggesting cytokinesis dysfunction. The survival of CYP51RNAi Doxycycline-treated mice (p = 0.053 and of CYP51RNAi 5-day pre-induced Doxycycline-treated mice (p = 0.008 were improved compared to WT showing a CYP51 RNAi effect on trypanosomal virulence in mice. The posaconazole concentrations that inhibited parasite growth by 50% (IC50 were 8.5, 2.7, 1.6 and 0.12 μM for T. b. brucei 427 90-13, T. b. brucei Antat 1.1, T. b. gambiense Feo (Feo/ITMAP/1893 and T. b. gambiense Biyamina (MHOM/SD/82, respectively. During infection with these last three virulent strains, posaconazole-eflornithine and nifurtimox-eflornithine combinations showed similar improvement in mice survival (p≤0.001. Our results provide support for a CYP51 targeting based treatment in HAT. Thus posaconazole used in combination may represent a therapeutic

  14. Trypanosoma brucei CYP51: Essentiality and Targeting Therapy in an Experimental Model.

    Science.gov (United States)

    Dauchy, Frédéric-Antoine; Bonhivers, Mélanie; Landrein, Nicolas; Dacheux, Denis; Courtois, Pierrette; Lauruol, Florian; Daulouède, Sylvie; Vincendeau, Philippe; Robinson, Derrick R

    2016-11-01

    Trypanosoma brucei gambiense is the main causative agent of Human African Trypanosomiasis (HAT), also known as sleeping sickness. Because of limited alternatives and treatment toxicities, new therapeutic options are urgently needed for patients with HAT. Sterol 14alpha-demethylase (CYP51) is a potential drug target but its essentiality has not been determined in T. brucei. We used a tetracycline-inducible RNAi system to assess the essentiality of CYP51 in T. brucei bloodstream form (BSF) cells and we evaluated the effect of posaconazole, a well-tolerated triazole drug, within a panel of virulent strains in vitro and in a murine model. Expression of CYP51 in several T. brucei cell lines was demonstrated by western blot and its essentiality was demonstrated by RNA interference (CYP51RNAi) in vitro. Following reduction of TbCYP51 expression by RNAi, cell growth was reduced and eventually stopped compared to WT or non-induced cells, showing the requirement of CYP51 in T. brucei. These phenotypes were rescued by addition of ergosterol. Additionally, CYP51RNAi induction caused morphological defects with multiflagellated cells (pnifurtimox-eflornithine combinations showed similar improvement in mice survival (p≤0.001). Our results provide support for a CYP51 targeting based treatment in HAT. Thus posaconazole used in combination may represent a therapeutic alternative for trypanosomiasis.

  15. Wild chimpanzees are infected by Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Milan Jirků

    2015-12-01

    Finally, we demonstrated that the mandrill serum was able to efficiently lyse T. b. brucei and T. b. rhodesiense, and to some extent T. b. gambiense, while the chimpanzee serum failed to lyse any of these subspecies.

  16. Extracellular-signal regulated kinase 8 of Trypanosoma brucei uniquely phosphorylates its proliferating cell nuclear antigen homolog and reveals exploitable properties.

    Science.gov (United States)

    Valenciano, Ana L; Knudsen, Giselle M; Mackey, Zachary B

    2016-10-17

    The Trypanosoma brucei subspecies T. brucei gambiense and T. brucei rhodesiense are vector-borne pathogens that cause sleeping sickness also known as Human African Trypanosomiasis (HAT), which is fatal if left untreated. The drugs that treat HAT are ineffective and cause toxic side effects. One strategy for identifying safer and more effective HAT drugs is to therapeutically exploit essential gene targets in T. brucei. Genes that make up a basic mitogen-activated protein kinase (MAPK) network are present in T. brucei. Tb927.10.5140 encodes an essential MAPK that is homologous to the human extracellular-signal regulated kinase 8 (HsERK8) which forms a tight complex with the replication factor proliferating cell nuclear antigen (PCNA) to stabilize intracellular PCNA levels. Here we demonstrate that (TbPCNA) is uniquely phos-phorylated on serine (S) and threonine (T) residues in T. brucei and that TbERK8 phosphorylates TbPCNA at each of these residues. The ability of an ERK8 homolog to phosphorylate a PCNA homolog is a novel biochemical property that is first demonstrated here in T. brucei and may be unique to this pathogen. We demonstrate that the potent HsERK8 inhibitor Ro318220, has an IC50 for TbERK8 that is several hundred times higher than its reported IC50 for HsERK8. This indicated that the active sites of TbERK8 and HsERK8 can be selectively inhibited, which provides a rational basis for discovering inhibitors that specifically target this essential parasite MAPK to kill the parasite.

  17. INFECTED WITH TRYPANOSOMA BRUCEI BRUCEI

    African Journals Online (AJOL)

    v brucei infection where for example tant components of extra-cellular the parasite infectivity potential and toxicological effects have been sues in animal. They are ... homeostasis (1,2, 3). With a unique ability to main- tain the cellular contents and ions stable concentrations, Trypano- soma b. brucei, to which humans.

  18. Trypanosoma brucei Invasion and T-Cell Infiltration of the Brain Parenchyma in Experimental Sleeping Sickness: Timing and Correlation with Functional Changes.

    Directory of Open Access Journals (Sweden)

    Claudia Laperchia

    2016-12-01

    Full Text Available The timing of Trypanosoma brucei entry into the brain parenchyma to initiate the second, meningoencephalitic stage of human African trypanosomiasis or sleeping sickness is currently debated and even parasite invasion of the neuropil has been recently questioned. Furthermore, the relationship between neurological features and disease stage are unclear, despite the important diagnostic and therapeutic implications.Using a rat model of chronic Trypanosoma brucei brucei infection we determined the timing of parasite and T-cell neuropil infiltration and its correlation with functional changes. Parasite DNA was detected using trypanosome-specific PCR. Body weight and sleep structure alterations represented by sleep-onset rapid eye movement (SOREM periods, reported in human and experimental African trypanosomiasis, were monitored. The presence of parasites, as well as CD4+ and CD8+ T-cells in the neuropil was assessed over time in the brain of the same animals by immunocytochemistry and quantitative analyses.Trypanosome DNA was present in the brain at day 6 post-infection and increased more than 15-fold by day 21. Parasites and T-cells were observed in the parenchyma from day 9 onwards. Parasites traversing blood vessel walls were observed in the hypothalamus and other brain regions. Body weight gain was reduced from day 7 onwards. SOREM episodes started in most cases early after infection, with an increase in number and duration after parasite neuroinvasion.These findings demonstrate invasion of the neuropil over time, after an initial interval, by parasites and lymphocytes crossing the blood-brain barrier, and show that neurological features can precede this event. The data thus challenge the current clinical and cerebrospinal fluid criteria of disease staging.

  19. About Trypanosoma brucei gambiense , the causative agent of the ...

    African Journals Online (AJOL)

    This must consider it within the whole context of "most-neglected diseases" but some findings obtained through biotechnology are discussed in terms of epidemiology and control applications. Key words: Human African Trypanosomiasis, neglected disease, biotechnologies. African Journal of Biotechnology Vol. 2 (12), pp.

  20. About Trypanosoma brucei gambiense, the causative agent of the ...

    African Journals Online (AJOL)

    Admin

    Since the discovery of this pathology at the beginning of 20th century (e.g. Bruce and Nabarro, 1903),. HAT has killed several hundred thousands of individuals in Africa, mainly in Central part of the continent (Martin et al., 1909; W.H.O., 1998). Although the epidemic of 1920-. 1930's was successfully controlled thanks to Dr.

  1. Syndromic algorithms for detection of gambiense human African trypanosomiasis in South Sudan.

    Directory of Open Access Journals (Sweden)

    Jennifer J Palmer

    Full Text Available Active screening by mobile teams is considered the best method for detecting human African trypanosomiasis (HAT caused by Trypanosoma brucei gambiense but the current funding context in many post-conflict countries limits this approach. As an alternative, non-specialist health care workers (HCWs in peripheral health facilities could be trained to identify potential cases who need testing based on their symptoms. We explored the predictive value of syndromic referral algorithms to identify symptomatic cases of HAT among a treatment-seeking population in Nimule, South Sudan.Symptom data from 462 patients (27 cases presenting for a HAT test via passive screening over a 7 month period were collected to construct and evaluate over 14,000 four item syndromic algorithms considered simple enough to be used by peripheral HCWs. For comparison, algorithms developed in other settings were also tested on our data, and a panel of expert HAT clinicians were asked to make referral decisions based on the symptom dataset. The best performing algorithms consisted of three core symptoms (sleep problems, neurological problems and weight loss, with or without a history of oedema, cervical adenopathy or proximity to livestock. They had a sensitivity of 88.9-92.6%, a negative predictive value of up to 98.8% and a positive predictive value in this context of 8.4-8.7%. In terms of sensitivity, these out-performed more complex algorithms identified in other studies, as well as the expert panel. The best-performing algorithm is predicted to identify about 9/10 treatment-seeking HAT cases, though only 1/10 patients referred would test positive.In the absence of regular active screening, improving referrals of HAT patients through other means is essential. Systematic use of syndromic algorithms by peripheral HCWs has the potential to increase case detection and would increase their participation in HAT programmes. The algorithms proposed here, though promising, should be

  2. Immune trypanolysis test with blood spotted on filter paper for epidemiological surveillance of sleeping sickness.

    Science.gov (United States)

    Camara, Oumou; Camara, Mamadou; Lejon, Veerle; Ilboudo, Hamidou; Sakande, Hassane; Léno, Mamadou; Büscher, Philippe; Bucheton, Bruno; Jamonneau, Vincent

    2014-07-01

    The immune trypanolysis test (TL) is an accurate sero-diagnostic tool increasingly implemented for sleeping sickness medical surveillance, but it is restricted to the reference laboratories. To facilitate storage and transport of the test specimen, we developed a protocol for the examination of blood spotted on filter paper (TL-fp) that can be stored and shipped at ambient temperature. We compared its performance with the classical TL on plasma (TL-pl) that needs to be kept frozen until use. The study was conducted in active foci of the Republic of Guinea. In total, 438 specimens from treated and untreated sleeping sickness patients and serological suspects were tested with both methods. TL-fp gave significantly less positive results than TL-pl, but all the confirmed sleeping sickness cases were positive with the TL-fp protocol. TL-fp appears to offer a good compromise between feasibility and sensitivity to detect currently infected subjects who play a role in the transmission of Trypanosoma brucei gambiense and is useful for contributing to the elimination of gambiense sleeping sickness. © 2014 John Wiley & Sons Ltd.

  3. Haematology of experimental Trypanosoma brucei rhodesiense ...

    African Journals Online (AJOL)

    Haematological aberrations associated with human infective trypanosomes were investigated in the vervet monkey model of the Rhodesian sleeping sickness. Four monkeys were infected intravenously with 104 Trypanosoma brucei rhodesiense and monitored for changes in the blood profile using a haematological ...

  4. Protective effect of humus extract against Trypanosoma brucei infection in mice.

    Science.gov (United States)

    Kodama, Hiroshi; Denso; Okazaki, Fumi; Ishida, Saeko

    2008-11-01

    Humic substances are formed during the decomposition of organic matter in humus, and are found in many natural environments in which organic materials and microorganisms are present. Oral administration of humus extract to mice successfully induced effective protection against experimental challenge by the two subspecies, Trypanosoma brucei brucei and T. brucei gambiense. Mortality was most reduced among mice who received a 3% humus extract for 21 days in drinking water ad libitum. Spleen cells from humus-administered mice exhibited significant non-specific cytotoxic activity against L1210 mouse leukemia target cells. Also, spleen cells produced significantly higher amounts of Interferon-gamma when stimulated in vitro with Concanavalin A than cells from normal controls. These results clearly show that administration to mice of humus extract induced effective resistance against Trypanosoma infection. Enhancement of the innate immune system may be involved in host defense against trypanosomiasis.

  5. Identification of different trypanosome species in the mid-guts of tsetse flies of the Malanga (Kimpese sleeping sickness focus of the Democratic Republic of Congo

    Directory of Open Access Journals (Sweden)

    Simo Gustave

    2012-09-01

    Full Text Available Abstract Background The Malanga sleeping sickness focus of the Democratic Republic of Congo has shown an epidemic evolution of disease during the last century. However, following case detection and treatment, the prevalence of the disease decreased considerably. No active survey has been undertaken in this focus for a couple of years. To understand the current epidemiological status of sleeping sickness as well as the animal African trypanosomiasis in the Malanga focus, we undertook the identification of tsetse blood meals as well as different trypanosome species in flies trapped in this focus. Methods Pyramidal traps were use to trap tsetse flies. All flies caught were identified and live flies were dissected and their mid-guts collected. Fly mid-gut was used for the molecular identification of the blood meal source, as well as for the presence of different trypanosome species. Results About 949 Glossina palpalis palpalis were trapped; 296 (31.2% of which were dissected, 60 (20.3% blood meals collected and 57 (19.3% trypanosome infections identified. The infection rates were 13.4%, 5.1%, 3.5% and 0.4% for Trypanosoma congolense savannah type, Trypanosoma brucei s.l., Trypanosoma congolense forest type and Trypanosoma vivax, respectively. Three mixed infections including Trypanosoma brucei s.l. and Trypanosoma congolense savannah type, and one mixed infection of Trypanosoma vivax and Trypanosoma congolense savannah type were identified. Eleven Trypanosoma brucei gambiense infections were identified; indicating an active circulation of this trypanosome subspecies. Of all the identified blood meals, about 58.3% were identified as being taken on pigs, while 33.3% and 8.3% were from man and other mammals, respectively. Conclusion The presence of Trypanosoma brucei in tsetse mid-guts associated with human blood meals is indicative of an active transmission of this parasite between tsetse and man. The considerable number of pig blood meals combined

  6. Identification of different trypanosome species in the mid-guts of tsetse flies of the Malanga (Kimpese) sleeping sickness focus of the Democratic Republic of Congo.

    Science.gov (United States)

    Simo, Gustave; Silatsa, Barberine; Flobert, Njiokou; Lutumba, Pascal; Mansinsa, Philemon; Madinga, Joule; Manzambi, Emile; De Deken, Reginald; Asonganyi, Tazoacha

    2012-09-19

    The Malanga sleeping sickness focus of the Democratic Republic of Congo has shown an epidemic evolution of disease during the last century. However, following case detection and treatment, the prevalence of the disease decreased considerably. No active survey has been undertaken in this focus for a couple of years. To understand the current epidemiological status of sleeping sickness as well as the animal African trypanosomiasis in the Malanga focus, we undertook the identification of tsetse blood meals as well as different trypanosome species in flies trapped in this focus. Pyramidal traps were use to trap tsetse flies. All flies caught were identified and live flies were dissected and their mid-guts collected. Fly mid-gut was used for the molecular identification of the blood meal source, as well as for the presence of different trypanosome species. About 949 Glossina palpalis palpalis were trapped; 296 (31.2%) of which were dissected, 60 (20.3%) blood meals collected and 57 (19.3%) trypanosome infections identified. The infection rates were 13.4%, 5.1%, 3.5% and 0.4% for Trypanosoma congolense savannah type, Trypanosoma brucei s.l., Trypanosoma congolense forest type and Trypanosoma vivax, respectively. Three mixed infections including Trypanosoma brucei s.l. and Trypanosoma congolense savannah type, and one mixed infection of Trypanosoma vivax and Trypanosoma congolense savannah type were identified. Eleven Trypanosoma brucei gambiense infections were identified; indicating an active circulation of this trypanosome subspecies. Of all the identified blood meals, about 58.3% were identified as being taken on pigs, while 33.3% and 8.3% were from man and other mammals, respectively. The presence of Trypanosoma brucei in tsetse mid-guts associated with human blood meals is indicative of an active transmission of this parasite between tsetse and man. The considerable number of pig blood meals combined with the circulation of Trypanosoma brucei gambiense in this focus

  7. What happens when Trypanosoma brucei leaves Africa.

    Science.gov (United States)

    Jensen, Robert E; Simpson, Larry; Englund, Paul T

    2008-10-01

    Julius Lukes and co-workers evaluated the evolutionary origin of Trypanosoma equiperdum and Trypanosoma evansi, parasites that cause horse and camel diseases. Although similar to T. brucei, the sleeping-sickness parasite, these trypanosomes do not cycle through the tsetse fly and have been able to spread beyond Africa. Transmission occurs sexually, or via blood-sucking flies or vampire bats. They concluded that these parasites, which resemble yeast petite mutants, are T. brucei sub-species, which have evolved recently through changes in mitochondrial DNA.

  8. Non-radioactive method for labelling Trypanosoma brucei brucei ...

    African Journals Online (AJOL)

    It was observed that (i) the biological activities of the T.brucei brucei like the motility, viability, and growth were not affected adversely by the biotinylation; (ii) as little as 100ug Sulfo-NHS-LC-Biotin was enough to label about 6x106 Trypanosoma Brucei Brucei; (iii) high temperature appears to have adverse effect on the ...

  9. [Some new cases of congenital human African trypanosomiasis (T. gambiense) (author's transl)].

    Science.gov (United States)

    Sina, G; Testa, G; Triolo, N; Trova, P; Cramet, B

    1979-01-01

    The authors report three cases of congenital transmission of T. gambiense. In two cases, the parasite has been found in the blood of the umbilical cord. In the third case, it has been found twenty hours after birth in the peripherical blood of a new born child whose mother was affected by trypanosomiasis. They report also two cases of pregnant mothers with sleeping sickness, whose children were born-unaffected by the disease. The authors believe that the placental transmission of the human african trypanosomiasis is more frequent than thought.

  10. Population genetic structure and cladistic analysis of Trypanosoma brucei isolates

    NARCIS (Netherlands)

    Agbo, E.C.; Clausen, P.H.; Buscher, P.; Majiwa, P.A.O.; Pas, te M.F.W.; Claassen, E.

    2003-01-01

    Using a novel multilocus DNA marker analysis method, we studied the population genetic structure of Trypansoma brucei stocks and derived clones isolated from animal and rhodesiense sleeping sickness patients during a national sleeping sickness control program in Mukono district, Uganda. We then

  11. Is sleeping sickness a circadian disorder? The serotonergic hypothesis.

    Science.gov (United States)

    Buguet, A

    1999-07-01

    Patients with human African trypanosomiasis (HAT, sleeping sickness), due to the inoculation of Trypanosoma brucei gambiense or rhodesiense by the tsetse fly, are "sleepy by day and restless by night." The first 24 h polysomnographic recording (electroencephalogram [EEG], electromyogram [EMG], electrooculogram [EOG]), showing a disappearance of the 24 h rhythmicity of sleep and wakefulness, was performed in 1988. Thereafter, our team recorded 18 patients and 6 control volunteers at bed rest during 24 h sessions. Blood samples were taken hourly from 8 of the patients through a venous catheter and every 10 minutes from the remaining 10 patients. Plasma cortisol, prolactin, growth hormone (GH), melatonin, and plasma renin activity were analyzed. No disruptions of the circadian rhythms of sleep and wakefulness were described in the 6 healthy African subjects, and there also were no disturbances of 24 h hormone profiles. The patients experienced a dysregulation of the circadian rhythmicity of sleep and wakefulness that was proportional to the severity of the disease. Sleep onset rapid eye movement (REM) episodes were more frequent in the most severely sick patients, who also showed major disruptions in the 24 h plasma hormonal profiles, with intermediate profiles being observed at earlier stages of the sickness. However, the relationship between hormonal secretions and the states of vigilance persisted. Contrary to the other hormones, melatonin secretion remained undisturbed. These findings indicate that, at the stage of meningoencephalitis, HAT represents a dysregulation of the sleep-wake cycle and sleep structure, rather than a hypersomnia; this dysregulation is proportional to the degree of severity of the clinical and biological symptoms. It is accompanied by a circadian dysrhythmia of hormonal secretions, although the relationship between hormone pulses and sleep states is preserved. We therefore favor the involvement of the serotonergic raphe nuclei

  12. Trypanosoma brucei Plimmer & Bradford, 1899 is a synonym of T. evansi (Steel, 1885) according to current knowledge and by application of nomenclature rules.

    Science.gov (United States)

    Molinari, Jesús; Moreno, S Andrea

    2018-02-06

    Proper application of the principles of biological nomenclature is fundamental for scientific and technical communication about organisms. As other scientific disciplines, taxonomy inherently is open to change, thus species names cannot be final and immutable. Nevertheless, altering the names of organisms of high economical, medical, or veterinary importance can become a complex challenge between the scientific need to have correct classifications, and the practical ideal of having fixed classifications. Trypanosoma evansi (Steel, 1885), T. brucei Plimmer & Bradford, 1899 and T. equiperdum Doflein, 1901 are important parasites of mammals. According to current knowledge, the three names are synonyms of a single trypanosome species, the valid name of which should be T. evansi by the mandatory application of the Principle of Priority of zoological nomenclature. Subspecies known as T. brucei brucei Plimmer & Bradford, 1899, T. b. gambiense Dutton, 1902 and T. b. rhodesiense Stephens & Fantham, 1910 should be referred to respectively as T. evansi evansi (Steel, 1885), T. e. gambiense and T. e. rhodesiense. The polyphyletic groupings so far known as T. evansi and T. equiperdum should be referred respectively to as surra- and dourine-causing strains of T. e. evansi. Likewise, trypanosomes so far known as T. b. brucei should be referred to as nagana-causing strains of T. e. evansi. Though it modifies the scientific names of flagship human and animal parasites, the amended nomenclature proposed herein should be adopted because it reflects phylogenetic and biological advancements, fixes errors, and is simpler than the existing classificatory system.

  13. Transcriptional analyses of Trypanosoma brucei gambiense from infected mice and in vitro culture

    OpenAIRE

    Kuboki, Noritaka; Kibe, Michael K; Thekisoe, Oriel M. M.; Sugimoto, Chihiro; Inoue, Noboru

    2007-01-01

    With the hypothesis that African trypanosomes could have in vivo specific genes for adaptation to host’s environment, the present study was conducted by using suppressive subtractive hybridization (SSH) technique to seek the highly expressed genes especially in host. A total of 328 clones from the in vivo SSH library and that of 160 clones from the in vitro SSH library were analyzed in order to determine their expression levels, but none of the above-mentioned genes showed differential expres...

  14. Taxonomy Icon Data: Trypanosoma brucei [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available Trypanosoma brucei Trypanosoma brucei Trypanosoma_brucei_L.png Trypanosoma_brucei_NL.png Trypanosoma_bruce...i_S.png Trypanosoma_brucei_NS.png http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Trypanosoma+bruce...i&t=L http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Trypanosoma+brucei&t=NL http://bioscie...ncedbc.jp/taxonomy_icon/icon.cgi?i=Trypanosoma+brucei&t=S http://biosciencedbc.jp.../taxonomy_icon/icon.cgi?i=Trypanosoma+brucei&t=NS http://togodb.biosciencedbc.jp/togodb/view/taxonomy_icon_comment_en?species_id=121 ...

  15. Hepatic response in Trypanosomia brucei brucei infected-rats ...

    African Journals Online (AJOL)

    Ethanol leaf extract of Tithonia diversifolia was investigated for its hepato-curative activity in Trypanosoma brucei brucei infected-rats. The phytochemical compositions of the plant extract were also evaluated. The leaf extract was administered 14 days post-infection at dose of 200 and 400 mg/kg orally once daily.

  16. Phenolic Constituents of Medicinal Plants with Activity against Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Ya Nan Sun

    2016-04-01

    Full Text Available Neglected tropical diseases (NTDs affect over one billion people all over the world. These diseases are classified as neglected because they impact populations in areas with poor financial conditions and hence do not attract sufficient research investment. Human African Trypanosomiasis (HAT or sleeping sickness, caused by the parasite Trypanosoma brucei, is one of the NTDs. The current therapeutic interventions for T. brucei infections often have toxic side effects or require hospitalization so that they are not available in the rural environments where HAT occurs. Furthermore, parasite resistance is increasing, so that there is an urgent need to identify novel lead compounds against this infection. Recognizing the wide structural diversity of natural products, we desired to explore and identify novel antitrypanosomal chemotypes from a collection of natural products obtained from plants. In this study, 440 pure compounds from various medicinal plants were tested against T. brucei by in a screening using whole cell in vitro assays. As the result, twenty-two phenolic compounds exhibited potent activity against cultures of T. brucei. Among them, eight compounds—4, 7, 11, 14, 15, 18, 20, and 21—showed inhibitory activity against T. brucei, with IC50 values below 5 µM, ranging from 0.52 to 4.70 μM. Based on these results, we attempt to establish some general trends with respect to structure-activity relationships, which indicate that further investigation and optimization of these derivatives might enable the preparation of potentially useful compounds for treating HAT.

  17. Steroid Alkaloids from Holarrhena africana with Strong Activity against Trypanosoma brucei rhodesiense

    OpenAIRE

    Charles Okeke Nnadi; Ngozi Justina Nwodo; Marcel Kaiser; Reto Brun; Thomas J. Schmidt

    2017-01-01

    In our continued search for natural compounds with activity against Trypanosoma brucei, causative agent of human African trypanosomiasis (HAT, “sleeping sickness”), we have investigated extracts from the leaves and bark of the West African Holarrhena africana (syn. Holarrhena floribunda; Apocynaceae). The extracts and their alkaloid-enriched fractions displayed promising in vitro activity against bloodstream forms of T. brucei rhodesiense (Tbr; East African HAT). Bioactivity-guided chromatogr...

  18. Molecular variation of Trypanosoma brucei subspecies as revealed by AFLP fingerprinting.

    Science.gov (United States)

    Agbo, E E C; Majiwa, P A O; Claassen, H J H M; te Pas, M F W

    2002-04-01

    Genetic analysis of Trypanosoma spp. depends on the detection of variation between strains. We have used the amplified fragment length polymorphism (AFLP) technique to develop a convenient and reliable method for genetic characterization of Trypanosome (sub)species. AFLP accesses multiple independent sites within the genome and would allow a better definition of the relatedness of different Trypanosome (sub)species. Nine isolates (3 from each T. brucei subspecies) were tested with 40 AFLP primer combinations to identify the most appropriate pairs of restriction endonucleases and selective primers. Primers based on the recognition sequences of EcoRI and BglII were chosen and used to analyse 31 T. brucei isolates. Similarity levels calculated with the Pearson correlation coefficient ranged from 15 to 98%, and clusters were determined using the unweighted pair-group method using arithmetic averages (UPGMA). At the intraspecific level, AFLP fingerprints were grouped by numerical analysis in 2 main clusters, allowing a clear separation of T. b. gambiense (cluster I) from T. b. brucei and T. b. rhodesiense isolates (cluster II). Interspecies evaluation of this customized approach produced heterogeneous AFLP patterns, with unique genetic markers, except for T. evansi and T. equiperdum, which showed identical patterns and clustered together.

  19. SUMOylation in Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Cornelia Andrea Klein

    2013-10-01

    Full Text Available Small ubiquitin like modifier (SUMO proteins are involved in many processes in eukaryotes. We here show that Trypanosoma brucei SUMO (Tb927.5.3210 modifies many proteins. The levels of SUMOylation were unaffected by temperature changes but were increased by severe oxidative stress. We obtained evidence that trypanosome homologues of the SUMO conjugating enzyme Ubc9 (Tb927.2.2460 and the SUMO-specific protease SENP (Tb927.9.2220 are involved in SUMOylation and SUMO removal, respectively.

  20. Gambiense Sleeping Sickness In The Abraka Region Of Delta State ...

    African Journals Online (AJOL)

    Five milliliters of venous blood was obtained from each patient into Ethlyene Diamine Tetraacetic acid (EDTA) bottle for microscopy. Lymph node fluid and tissue biopsies were taken from those with lymphadenopathy and CSF collected for screening from all the patients. Buffy coat layer (BCL) and deposits of lymph node ...

  1. Human and animal Trypanosomes in Cote d'Ivoire form a single breeding population.

    Directory of Open Access Journals (Sweden)

    Paul Capewell

    Full Text Available BACKGROUND: Trypanosoma brucei is the causative agent of African Sleeping Sickness in humans and contributes to the related veterinary disease, Nagana. T. brucei is segregated into three subspecies based on host specificity, geography and pathology. T. b. brucei is limited to animals (excluding some primates throughout sub-Saharan Africa and is non-infective to humans due to trypanolytic factors found in human serum. T. b. gambiense and T. b. rhodesiense are human infective sub-species. T. b. gambiense is the more prevalent human, causing over 97% of human cases. Study of T. b. gambiense is complicated in that there are two distinct groups delineated by genetics and phenotype. The relationships between the two groups and local T. b. brucei are unclear and may have a bearing on the evolution of the human infectivity traits. METHODOLOGY/PRINCIPAL FINDINGS: A collection of sympatric T. brucei isolates from Côte d'Ivoire, consisting of T. b. brucei and both groups of T. b. gambiense have previously been categorized by isoenzymes, RFLPs and Blood Incubation Infectivity Tests. These samples were further characterized using the group 1 specific marker, TgSGP, and seven microsatellites. The relationships between the T. b. brucei and T. b. gambiense isolates were determined using principal components analysis, neighbor-joining phylogenetics, STRUCTURE, FST, Hardy-Weinberg equilibrium and linkage disequilibrium. CONCLUSIONS/SIGNIFICANCE: Group 1 T. b. gambiense form a clonal genetic group, distinct from group 2 and T. b. brucei, whereas group 2 T. b. gambiense are genetically indistinguishable from local T. b. brucei. There is strong evidence for mating within and between group 2 T. b. gambiense and T. b. brucei. We found no evidence to support the hypothesis that group 2 T. b. gambiense are hybrids of group 1 and T. b. brucei, suggesting that human infectivity has evolved independently in groups 1 and 2 T. b. gambiense.

  2. Diagnostic accuracy of loopamp Trypanosoma brucei detection kit for diagnosis of human African trypanosomiasis in clinical samples.

    Directory of Open Access Journals (Sweden)

    Patrick Mitashi

    Full Text Available BACKGROUND: Molecular methods have great potential for sensitive parasite detection in the diagnosis of human African trypanosomiasis (HAT, but the requirements in terms of laboratory infrastructure limit their use to reference centres. A recently developed assay detects the Trypanozoon repetitive insertion mobile element (RIME DNA under isothermal amplification conditions and has been transformed into a ready-to-use kit format, the Loopamp Trypanosoma brucei. In this study, we have evaluated the diagnostic performance of the Loopamp Trypanosoma brucei assay (hereafter called LAMP in confirmed T.b. gambiense HAT patients, HAT suspects and healthy endemic controls from the Democratic Republic of the Congo (DRC. METHODOLOGY/PRINCIPAL FINDINGS: 142 T.b. gambiense HAT patients, 111 healthy endemic controls and 97 HAT suspects with unconfirmed status were included in this retrospective evaluation. Reference standard tests were parasite detection in blood, lymph or cerebrospinal fluid. Archived DNA from blood of all study participants was analysed in duplicate with LAMP. Sensitivity of LAMP in parasitologically confirmed cases was 87.3% (95% CI 80.9-91.8% in the first run and 93.0% (95% CI 87.5-96.1% in the second run. Specificity in healthy controls was 92.8% (95% CI 86.4-96.3% in the first run and 96.4% (95% CI 91.1-98.6% in the second run. Reproducibility was excellent with a kappa value of 0.81. CONCLUSIONS/SIGNIFICANCE: In this laboratory-based study, the Loopamp Trypanosoma brucei Detection Kit showed good diagnostic accuracy and excellent reproducibility. Further studies are needed to assess the feasibility of its routine use for diagnosis of HAT under field conditions.

  3. The genome of the African trypanosome Trypanosoma brucei.

    Science.gov (United States)

    Berriman, Matthew; Ghedin, Elodie; Hertz-Fowler, Christiane; Blandin, Gaëlle; Renauld, Hubert; Bartholomeu, Daniella C; Lennard, Nicola J; Caler, Elisabet; Hamlin, Nancy E; Haas, Brian; Böhme, Ulrike; Hannick, Linda; Aslett, Martin A; Shallom, Joshua; Marcello, Lucio; Hou, Lihua; Wickstead, Bill; Alsmark, U Cecilia M; Arrowsmith, Claire; Atkin, Rebecca J; Barron, Andrew J; Bringaud, Frederic; Brooks, Karen; Carrington, Mark; Cherevach, Inna; Chillingworth, Tracey-Jane; Churcher, Carol; Clark, Louise N; Corton, Craig H; Cronin, Ann; Davies, Rob M; Doggett, Jonathon; Djikeng, Appolinaire; Feldblyum, Tamara; Field, Mark C; Fraser, Audrey; Goodhead, Ian; Hance, Zahra; Harper, David; Harris, Barbara R; Hauser, Heidi; Hostetler, Jessica; Ivens, Al; Jagels, Kay; Johnson, David; Johnson, Justin; Jones, Kristine; Kerhornou, Arnaud X; Koo, Hean; Larke, Natasha; Landfear, Scott; Larkin, Christopher; Leech, Vanessa; Line, Alexandra; Lord, Angela; Macleod, Annette; Mooney, Paul J; Moule, Sharon; Martin, David M A; Morgan, Gareth W; Mungall, Karen; Norbertczak, Halina; Ormond, Doug; Pai, Grace; Peacock, Chris S; Peterson, Jeremy; Quail, Michael A; Rabbinowitsch, Ester; Rajandream, Marie-Adele; Reitter, Chris; Salzberg, Steven L; Sanders, Mandy; Schobel, Seth; Sharp, Sarah; Simmonds, Mark; Simpson, Anjana J; Tallon, Luke; Turner, C Michael R; Tait, Andrew; Tivey, Adrian R; Van Aken, Susan; Walker, Danielle; Wanless, David; Wang, Shiliang; White, Brian; White, Owen; Whitehead, Sally; Woodward, John; Wortman, Jennifer; Adams, Mark D; Embley, T Martin; Gull, Keith; Ullu, Elisabetta; Barry, J David; Fairlamb, Alan H; Opperdoes, Fred; Barrell, Barclay G; Donelson, John E; Hall, Neil; Fraser, Claire M; Melville, Sara E; El-Sayed, Najib M

    2005-07-15

    African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of Trypanosoma brucei. The 26-megabase genome contains 9068 predicted genes, including approximately 900 pseudogenes and approximately 1700 T. brucei-specific genes. Large subtelomeric arrays contain an archive of 806 variant surface glycoprotein (VSG) genes used by the parasite to evade the mammalian immune system. Most VSG genes are pseudogenes, which may be used to generate expressed mosaic genes by ectopic recombination. Comparisons of the cytoskeleton and endocytic trafficking systems with those of humans and other eukaryotic organisms reveal major differences. A comparison of metabolic pathways encoded by the genomes of T. brucei, T. cruzi, and Leishmania major reveals the least overall metabolic capability in T. brucei and the greatest in L. major. Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified.

  4. Adaptations of Trypanosoma brucei to gradual loss of kinetoplast DNA: Trypanosoma equiperdum and Trypanosoma evansi are petite mutants of T. brucei.

    Science.gov (United States)

    Lai, De-Hua; Hashimi, Hassan; Lun, Zhao-Rong; Ayala, Francisco J; Lukes, Julius

    2008-02-12

    Trypanosoma brucei is a kinetoplastid flagellate, the agent of human sleeping sickness and ruminant nagana in Africa. Kinetoplastid flagellates contain their eponym kinetoplast DNA (kDNA), consisting of two types of interlocked circular DNA molecules: scores of maxicircles and thousands of minicircles. Maxicircles have typical mitochondrial genes, most of which are translatable only after RNA editing. Minicircles encode guide RNAs, required for decrypting the maxicircle transcripts. The life cycle of T. brucei involves a bloodstream stage (BS) in vertebrates and a procyclic stage (PS) in the tsetse fly vector. Partial [dyskinetoplastidy (Dk)] or total [akinetoplastidy (Ak)] loss of kDNA locks the trypanosome in the BS form. Transmission between vertebrates becomes mechanical without PS and tsetse mediation, allowing the parasite to spread outside the African tsetse belt. Trypanosoma equiperdum and Trypanosoma evansi are agents of dourine and surra, diseases of horses, camels, and water buffaloes. We have characterized representative strains of T. equiperdum and T. evansi by numerous molecular and classical parasitological approaches. We show that both species are actually strains of T. brucei, which lost part (Dk) or all (Ak) of their kDNA. These trypanosomes are not monophyletic clades and do not qualify for species status. They should be considered two subspecies, respectively T. brucei equiperdum and T. brucei evansi, which spontaneously arose recently. Dk/Ak trypanosomes may potentially emerge repeatedly from T. brucei.

  5. Sleeping sickness in travelers - do they really sleep?

    Directory of Open Access Journals (Sweden)

    Karin Urech

    2011-11-01

    Full Text Available The number of imported Human African Trypanosomiasis (HAT cases in non-endemic countries has increased over the last years. The objective of this analysis is to describe the clinical presentation of HAT in Caucasian travelers. Literature was screened (MEDLINE, Pubmed using the terms "Human African Trypanosomiasis", "travelers" and "expatriates"; all European languages except Slavic ones were included. Publications without clinical description of patients were only included in the epidemiological analysis. Forty-five reports on Caucasians with T.b. rhodesiense and 15 with T.b. gambiense infections were included in the analysis of the clinical parameters. Both species have presented with fever (T.b. rhodesiense 97.8% and T.b. gambiense 93.3%, headache (50% each and a trypanosomal chancre (T.b. rhodesiense 84.4%, T.b. gambiense 46.7%. While sleeping disorders dominate the clinical presentation of HAT in endemic regions, there have been only rare reports in travelers: insomnia (T.b. rhodesiense 7.1%, T.b. gambiense 21.4%, diurnal somnolence (T.b. rhodesiense 4.8%, T.b. gambiense none. Surprisingly, jaundice has been seen in 24.2% of the Caucasian T.b. rhodesiense patients, but has never been described in HAT patients in endemic regions. These results contrast to the clinical presentation of T.b. gambiense and T.b. rhodesiense HAT in Africans in endemic regions, where the presentation of chronic T.b. gambiense and acute T.b. rhodesiense HAT is different. The analysis of 14 reports on T.b. gambiense HAT in Africans living in a non-endemic country shows that neurological symptoms such as somnolence (46.2%, motor deficit (64.3% and reflex anomalies (14.3% as well as psychiatric symptoms such as hallucinations (21.4% or depression (21.4% may dominate the clinical picture. Often, the diagnosis has been missed initially: some patients have even been hospitalized in psychiatric clinics. In travelers T.b. rhodesiense and gambiense present as acute illnesses

  6. Is there a suburban sleeping sickness in Libreville? | Kohagne ...

    African Journals Online (AJOL)

    Background: The transmission of sleeping sickness occurs primarily in rural areas, and exposed populations are those living from rural activities such as agriculture, fishing, animal husbandry or hunting. However, urban and suburban foci are more and more reported in T. b. gambiense areas. In Libreville town, sleeping ...

  7. Sleep

    Science.gov (United States)

    ... REM sleep? What is the effect of sleep deprivation? What are sleep myths? What are sleep disorders? ... Some hormones produced during sleep affect the body's use of energy. This may be how inadequate sleep ...

  8. Trypanosoma vivax, T. congolense “forest type” and T. simiae: prevalence in domestic animals of sleeping sickness foci of Cameroon

    Science.gov (United States)

    Nimpaye, H.; Njiokou, F.; Njine, T.; Njitchouang, G.R.; Cuny, G.; Herder, S.; Asonganyi, T.; Simo, G.

    2011-01-01

    In order to better understand the epidemiology of Human and Animal trypanosomiasis that occur together in sleeping sickness foci, a study of prevalences of animal parasites (Trypanosoma vivax, T. congolense “forest type”, and T. simiae) infections was conducted on domestic animals to complete the previous work carried on T. brucei gambiense prevalence using the same animal sample. 875 domestic animals, including 307 pigs, 264 goats, 267 sheep and 37 dogs were sampled in the sleeping sickness foci of Bipindi, Campo, Doumé and Fontem in Cameroon. The polymerase chain reaction (PCR) based method was used to identify these trypanosome species. A total of 237 (27.08%) domestic animals were infected by at least one trypanosome species. The prevalence of T. vivax, T. congolense “forest type” and T. simiae were 20.91%, 11.42% and 0.34% respectively. The prevalences of T. vivax and T. congolense “forest type” differed significantly between the animal species and between the foci (p < 0.0001); however, these two trypanosomes were found in all animal species as well as in all the foci subjected to the study. The high prevalences of T. vivax and T. congolense “forest type” in Bipindi and Fontem-Center indicate their intense transmission in these foci. PMID:21678793

  9. Monitoring the use of nifurtimox-eflornithine combination therapy (NECT in the treatment of second stage gambiense human African trypanosomiasis

    Directory of Open Access Journals (Sweden)

    Franco JR

    2012-08-01

    Full Text Available Jose R Franco,1 Pere P Simarro,1 Abdoulaye Diarra,2 Jose A Ruiz-Postigo,3 Mireille Samo,1 Jean G Jannin11World Health Organization, Control of Neglected Tropical Diseases, Innovative and Intensified Disease Management, Geneva, Switzerland; 2World Health Organization, Regional Office for Africa, Brazzaville, Congo; 3World Health Organization, Communicable Disease Control, Control of Tropical Diseases and Zoonoses Regional Office for the Eastern Mediterranean, Cairo, EgyptAbstract: After inclusion of the nifurtimox-eflornithine combination therapy (NECT in the Model List of Essential Medicines for the treatment of second-stage gambiense human African trypanosomiasis (HAT, the World Health Organization, in collaboration with National Sleeping Sickness Control Programs and nongovernmental organizations set up a pharmacovigilance system to assess the safety and efficacy of NECT during its routine use. Data were collected for 1735 patients treated with NECT in nine disease endemic countries during 2010–2011. At least one adverse event (AE was described in 1043 patients (60.1% and a total of 3060 AE were reported. Serious adverse events (SAE were reported for 19 patients (1.1% of treated, leading to nine deaths (case fatality rate of 0.5%. The most frequent AE were gastrointestinal disorders (vomiting/nausea and abdominal pain, followed by headache, musculoskeletal pains, and vertigo. The most frequent SAE and cause of death were convulsions, fever, and coma that were considered as reactive encephalopathy. Two hundred and sixty-two children below 15 years old were treated. The characteristics of AE were similar to adults, but the major AE were less frequent in children with only one SAE and no deaths registered in this group. Gastrointestinal problems (vomiting and abdominal pain were more frequent than in adults, but musculoskeletal pains, vertigo, asthenia, neuropsychiatric troubles (headaches, seizures, tremors, hallucinations, insomnia were less

  10. An Overview of Trypanosoma brucei Infections: An Intense Host-Parasite Interaction.

    Science.gov (United States)

    Ponte-Sucre, Alicia

    2016-01-01

    Trypanosoma brucei rhodesiense and T. brucei gambiense, the causative agents of Human African Trypanosomiasis, are transmitted by tsetse flies. Within the vector, the parasite undergoes through transformations that prepares it to infect the human host. Sequentially these developmental stages are the replicative procyclic (in which the parasite surface is covered by procyclins) and trypo-epimastigote forms, as well as the non-replicative, infective, metacyclic form that develops in the vector salivary glands. As a pre-adaptation to their life in humans, metacyclic parasites begin to express and be densely covered by the Variant Surface Glycoprotein (VSG). Once the metacyclic form invades the human host the parasite develops into the bloodstream form. Herein the VSG triggers a humoral immune response. To avoid this humoral response, and essential for survival while in the bloodstream, the parasite changes its cover periodically and sheds into the surroundings the expressed VSG, thus evading the consequences of the immune system activation. Additionally, tools comparable to quorum sensing are used by the parasite for the successful parasite transmission from human to insect. On the other hand, the human host promotes clearance of the parasite triggering innate and adaptive immune responses and stimulating cytokine and chemokine secretion. All in all, the host-parasite interaction is extremely active and leads to responses that need multiple control sites to develop appropriately.

  11. Novel molecular mechanism for targeting the parasite Trypanosoma brucei with snake venom toxins

    DEFF Research Database (Denmark)

    Martos Esteban, Andrea; Laustsen, Andreas Hougaard; Carrington, Mark

    Trypanosoma brucei is a parasitic protozoan species capable to infecting insect vectors whose bite further produces African sleeping sickness inhuman beings. During parasites’extracellular lives in the mammalian host, its outer coat, mainly composedof Variable surface glycoproteins (VSGs)[2], und...

  12. Malleable mitochondrion of Trypanosoma brucei.

    Science.gov (United States)

    Verner, Zdeněk; Basu, Somsuvro; Benz, Corinna; Dixit, Sameer; Dobáková, Eva; Faktorová, Drahomíra; Hashimi, Hassan; Horáková, Eva; Huang, Zhenqiu; Paris, Zdeněk; Peña-Diaz, Priscila; Ridlon, Lucie; Týč, Jiří; Wildridge, David; Zíková, Alena; Lukeš, Julius

    2015-01-01

    The importance of mitochondria for a typical aerobic eukaryotic cell is undeniable, as the list of necessary mitochondrial processes is steadily growing. Here, we summarize the current knowledge of mitochondrial biology of an early-branching parasitic protist, Trypanosoma brucei, a causative agent of serious human and cattle diseases. We present a comprehensive survey of its mitochondrial pathways including kinetoplast DNA replication and maintenance, gene expression, protein and metabolite import, major metabolic pathways, Fe-S cluster synthesis, ion homeostasis, organellar dynamics, and other processes. As we describe in this chapter, the single mitochondrion of T. brucei is everything but simple and as such rivals mitochondria of multicellular organisms. Copyright © 2015. Published by Elsevier Inc.

  13. The kinetoplast of DNA of Trypanosoma gambiense: comparison with the kDNA of Trypanosoma equiperdum.

    Science.gov (United States)

    Riou, G; Barrois, M

    1981-10-01

    The molecular components of the kinetoplast DNA (kDNA) network of Trypanosoma gambiense have been studied and compared with those of the very closely related species T. equiperdum, previously studied in detail. The kDNA of T. gambiense contains about 80 maxicircles of 20 kilobase pairs and 4000 minicircles of 1 kilobase pairs. The restriction cleavage sites of 7 restriction endonucleases have been mapped on the T. gambiense maxicircle. The majority of these sites were also found in T. equiperdum maxicircles; however their relative positions which are different do not allow us to conclude to relatedness of maps. Maxicircles of the Cairn or of the rolling circle type have been observed and thought to be replicative intermediates. Experiments on renaturation kinetics and hybridization after blotting transfer, show that T. gambiense and T. equiperdum maxicircles have base sequences in common. The T. gambiense minicircles are heterogeneous in base sequence, in contrast to the T. equiperdum minicircles which are homogeneous. The minicircles of the two species have also common base sequences.

  14. Immunomodulatory activity of Buchholzia coriacea seed methanol extract on Trypanosoma brucei brucei infected mice.

    Science.gov (United States)

    Eze, James I; Ekelozie, Chioma F; Nweze, Nwakego E

    2017-12-01

    The seeds of Buchholzia coriacea Engler (Capparaceae) are used in Eastern Nigeria to treat feverish conditions, and to treat malaria and sleeping sickness that cause fever. The current study assesses the immunomodulatory activity of Buchholzia coriacea seed extract on Trypanosoma brucei brucei infected mice. Delayed hypersensitivity reaction, humoral antibody response and in-vivo leucocyte mobilization tests were assessed in three different experiments to determine the effect of the extract on immune response. Seventy-five (75) mice (25 mice per experiment) were used for the study and were each infected with 1.00 × 106 trypanosomes intra-peritoneally. Groups A, B and C were given 250, 500 and 1000 mg/kg of the extract, respectively, group D received 7.5 mg/kg body weight of levamisole and group E was the control. Sheep RBCs were used as antigen. The acute toxicity tests did not cause clinical signs or death within 24 h post treatment at all the doses tested. The extract inhibited delayed hypersensitivity reaction by 20.9 and 20.8% at 250 and 500 mg/kg, respectively, while at 1000 mg/kg, the paw size increased (-101.9%) when compared with the control. The extract elevated the antibody titre from 1.60 ± 0.40 for control to 8.00 ± 3.58 for 500 mg/kg group. The extract increased in total leucocytes counts. The extract has a very wide safety margin and was able to improve immune response. The results of the present study showed that Buchholzia coriacea seed methanol extract possesses immunostimulatory activity on trypanosome-infected mice.

  15. A tropical tale: how Naja nigricollis venom beats Trypanosoma brucei

    DEFF Research Database (Denmark)

    Martos Esteban, Andrea; Laustsen, Andreas Hougaard; Carrington, Mark

    Trypanosoma brucei is a parasitic protozoan species capable to infecting insect vectors whose bite further produces African sleeping sickness inhuman beings [1]. During the parasite’s extracellular life in the mammalian host,its outer coat, mainly composed of Variable Surface Glycoproteins (VSGs...

  16. Stearoyl-CoA desaturase is an essential enzyme for the parasitic protist Trypanosoma brucei

    Energy Technology Data Exchange (ETDEWEB)

    Alloatti, Andres [Instituto de Biologia Molecular y Celular de Rosario (IBR), CONICET, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Santa Fe (Argentina); Gupta, Shreedhara; Gualdron-Lopez, Melisa; Nguewa, Paul A. [Research Unit for Tropical Diseases, de Duve Institute and Laboratory of Biochemistry, Universite Catholique de Louvain, Brussels (Belgium); Altabe, Silvia G. [Instituto de Biologia Molecular y Celular de Rosario (IBR), CONICET, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Santa Fe (Argentina); Deumer, Gladys; Wallemacq, Pierre [Department of Clinical Chemistry, Cliniques Universitaires Saint-Luc, LTAP, Universite Catholique de Louvain, Brussels (Belgium); Michels, Paul A.M. [Research Unit for Tropical Diseases, de Duve Institute and Laboratory of Biochemistry, Universite Catholique de Louvain, Brussels (Belgium); Uttaro, Antonio D., E-mail: toniuttaro@yahoo.com.ar [Instituto de Biologia Molecular y Celular de Rosario (IBR), CONICET, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Santa Fe (Argentina)

    2011-08-26

    Highlights: {yields} Inhibiting {Delta}9 desaturase drastically changes T. brucei's fatty-acid composition. {yields} Isoxyl specifically inhibits the {Delta}9 desaturase causing a growth arrest. {yields} RNA interference of desaturase expression causes a similar effect. {yields} Feeding T. brucei-infected mice with Isoxyl decreases the parasitemia. {yields} 70% of Isoxyl-treated mice survived the trypanosome infection. -- Abstract: Trypanosoma brucei, the etiologic agent of sleeping sickness, is exposed to important changes in nutrients and temperature during its life cycle. To adapt to these changes, the fluidity of its membranes plays a crucial role. This fluidity, mediated by the fatty-acid composition, is regulated by enzymes named desaturases. We have previously shown that the oleoyl desaturase is essential for Trypanosoma cruzi and T. brucei. In this work, we present experimental support for the relevance of stearoyl-CoA desaturase (SCD) for T. brucei's survival, in both its insect or procyclic-form (PCF) and bloodstream-form (BSF) stages. We evaluated this essentiality in two different ways: by generating a SCD knocked-down parasite line using RNA interference, and by chemical inhibition of the enzyme with two compounds, Isoxyl and a thiastearate with the sulfur atom at position 10 (10-TS). The effective concentration for 50% growth inhibition (EC{sub 50}) of PCF was 1.0 {+-} 0.2 {mu}M for Isoxyl and 5 {+-} 2 {mu}M for 10-TS, whereas BSF appeared more susceptible with EC{sub 50} values 0.10 {+-} 0.03 {mu}M (Isoxyl) and 1.0 {+-} 0.6 {mu}M (10-TS). RNA interference showed to be deleterious for both stages of the parasite. In addition, T. brucei-infected mice were fed with Isoxyl, causing a reduction of the parasitemia and an increase of the rodents' survival.

  17. Non-cytochrome mediated mitochondrial ATP production in bloodstream form Trypanosoma brucei brucei

    NARCIS (Netherlands)

    Bienen, E. J.; Maturi, R. K.; Pollakis, G.; Clarkson, A. B.

    1993-01-01

    The life cycle of Trypanosoma brucei brucei involves a series of differentiation steps characterized by marked changes in mitochondrial development and function. The bloodstream forms of this parasite completely lack cytochromes and have not been considered to have any Krebs cycle function. It has

  18. The Flagellar Arginine Kinase in Trypanosoma brucei Is Important for Infection in Tsetse Flies.

    Directory of Open Access Journals (Sweden)

    Cher-Pheng Ooi

    Full Text Available African trypanosomes are flagellated parasites that cause sleeping sickness. Parasites are transmitted from one mammalian host to another by the bite of a tsetse fly. Trypanosoma brucei possesses three different genes for arginine kinase (AK including one (AK3 that encodes a protein localised to the flagellum. AK3 is characterised by the presence of a unique amino-terminal insertion that specifies flagellar targeting. We show here a phylogenetic analysis revealing that flagellar AK arose in two independent duplication events in T. brucei and T. congolense, the two species of African trypanosomes that infect the tsetse midgut. In T. brucei, AK3 is detected in all stages of parasite development in the fly (in the midgut and in the salivary glands as well as in bloodstream cells, but with predominance at insect stages. Genetic knockout leads to a slight reduction in motility and impairs parasite infectivity towards tsetse flies in single and competition experiments, both phenotypes being reverted upon expression of an epitope-tagged version of AK3. We speculate that this flagellar arginine kinase is important for T. brucei infection of tsetse, especially in the context of mixed infections and that its flagellar targeting relies on a system equivalent to that discovered for calflagins, a family of trypanosome flagellum calcium binding proteins.

  19. The Flagellar Arginine Kinase in Trypanosoma brucei Is Important for Infection in Tsetse Flies.

    Science.gov (United States)

    Ooi, Cher-Pheng; Rotureau, Brice; Gribaldo, Simonetta; Georgikou, Christina; Julkowska, Daria; Blisnick, Thierry; Perrot, Sylvie; Subota, Ines; Bastin, Philippe

    2015-01-01

    African trypanosomes are flagellated parasites that cause sleeping sickness. Parasites are transmitted from one mammalian host to another by the bite of a tsetse fly. Trypanosoma brucei possesses three different genes for arginine kinase (AK) including one (AK3) that encodes a protein localised to the flagellum. AK3 is characterised by the presence of a unique amino-terminal insertion that specifies flagellar targeting. We show here a phylogenetic analysis revealing that flagellar AK arose in two independent duplication events in T. brucei and T. congolense, the two species of African trypanosomes that infect the tsetse midgut. In T. brucei, AK3 is detected in all stages of parasite development in the fly (in the midgut and in the salivary glands) as well as in bloodstream cells, but with predominance at insect stages. Genetic knockout leads to a slight reduction in motility and impairs parasite infectivity towards tsetse flies in single and competition experiments, both phenotypes being reverted upon expression of an epitope-tagged version of AK3. We speculate that this flagellar arginine kinase is important for T. brucei infection of tsetse, especially in the context of mixed infections and that its flagellar targeting relies on a system equivalent to that discovered for calflagins, a family of trypanosome flagellum calcium binding proteins.

  20. Aquaglyceroporins Are the Entry Pathway of Boric Acid in Trypanosoma brucei.

    Science.gov (United States)

    Marsiccobetre, Sabrina; Rodríguez-Acosta, Alexis; Lang, Florian; Figarella, Katherine; Uzcátegui, Néstor L

    2017-05-01

    The boron element possesses a range of different effects on living beings. It is essential to beneficial at low concentrations, but toxic at excessive concentrations. Recently, some boron-based compounds have been identified as promising molecules against Trypanosoma brucei, the causative agent of sleeping sickness. However, until now, the boron metabolism and its access route into the parasite remained elusive. The present study addressed the permeability of T. brucei aquaglyceroporins (TbAQPs) for boric acid, the main natural boron species. To this end, the three TbAQPs were expressed in Saccharomyces cerevisiae and Xenopus laevis oocytes. Our findings in both expression systems showed that all three TbAQPs are permeable for boric acid. Especially TbAQP2 is highly permeable for this compound, displaying one of the highest conductances reported for a solute in these channels. Additionally, T. brucei aquaglyceroporin activities were sensitive to pH. Taken together, these results establish that TbAQPs are channels for boric acid and are highly efficient entry pathways for boron into the parasite. Our findings stress the importance of studying the physiological functions of boron and their derivatives in T. brucei, as well as the pharmacological implications of their uptake by trypanosome aquaglyceroporins. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Case Report Challenges in the diagnosis and management of ...

    African Journals Online (AJOL)

    Sleeping sickness also known as Human African try- panosomiasis is a disease of human which exists in two forms and is caused by infection with either Trypanoso- ma brucei rhodesiense (acute sleeping sickness, endemic in East and South Africa) or T.b. gambiense (chronic sleeping sickness, endemic in West and ...

  2. Reduced Mitochondrial Membrane Potential Is a Late Adaptation of Trypanosoma brucei brucei to Isometamidium Preceded by Mutations in the γ Subunit of the F1Fo-ATPase.

    Directory of Open Access Journals (Sweden)

    Anthonius A Eze

    2016-08-01

    Full Text Available Isometamidium is the main prophylactic drug used to prevent the infection of livestock with trypanosomes that cause Animal African Trypanosomiasis. As well as the animal infective trypanosome species, livestock can also harbor the closely related human infective subspecies T. b. gambiense and T. b. rhodesiense. Resistance to isometamidium is a growing concern, as is cross-resistance to the diamidine drugs diminazene and pentamidine.Two isometamidium resistant Trypanosoma brucei clones were generated (ISMR1 and ISMR15, being 7270- and 16,000-fold resistant to isometamidium, respectively, which retained their ability to grow in vitro and establish an infection in mice. Considerable cross-resistance was shown to ethidium bromide and diminazene, with minor cross-resistance to pentamidine. The mitochondrial membrane potentials of both resistant cell lines were significantly reduced compared to the wild type. The net uptake rate of isometamidium was reduced 2-3-fold but isometamidium efflux was similar in wild-type and resistant lines. Fluorescence microscopy and PCR analysis revealed that ISMR1 and ISMR15 had completely lost their kinetoplast DNA (kDNA and both lines carried a mutation in the nuclearly encoded γ subunit gene of F1 ATPase, truncating the protein by 22 amino acids. The mutation compensated for the loss of the kinetoplast in bloodstream forms, allowing near-normal growth, and conferred considerable resistance to isometamidium and ethidium as well as significant resistance to diminazene and pentamidine, when expressed in wild type trypanosomes. Subsequent exposure to either isometamidium or ethidium led to rapid loss of kDNA and a further increase in isometamidium resistance.Sub-lethal exposure to isometamidium gives rise to viable but highly resistant trypanosomes that, depending on sub-species, are infective to humans and cross-resistant to at least some diamidine drugs. The crucial mutation is in the F1 ATPase γ subunit, which

  3. Estimating the burden of rhodesiense sleeping sickness during an outbreak in Serere, eastern Uganda

    Directory of Open Access Journals (Sweden)

    Coleman Paul G

    2008-03-01

    Full Text Available Abstract Background Zoonotic sleeping sickness, or HAT (Human African Trypanosomiasis, caused by infection with Trypanosoma brucei rhodesiense, is an under-reported and neglected tropical disease. Previous assessments of the disease burden expressed as Disability-Adjusted Life Years (DALYs for this infection have not distinguished T.b. rhodesiense from infection with the related, but clinically distinct Trypanosoma brucei gambiense form. T.b. rhodesiense occurs focally, and it is important to assess the burden at the scale at which resource-allocation decisions are made. Methods The burden of T.b. rhodesiense was estimated during an outbreak of HAT in Serere, Uganda. We identified the unique characteristics affecting the burden of rhodesiense HAT such as age, severity, level of under-reporting and duration of hospitalisation, and use field data and empirical estimates of these to model the burden imposed by this and other important diseases in this study population. While we modelled DALYs using standard methods, we also modelled uncertainty of our parameter estimates through a simulation approach. We distinguish between early and late stage HAT morbidity, and used disability weightings appropriate for the T.b. rhodesiense form of HAT. We also use a model of under-reporting of HAT to estimate the contribution of un-reported mortality to the overall disease burden in this community, and estimate the cost-effectiveness of hospital-based HAT control. Results Under-reporting accounts for 93% of the DALY estimate of rhodesiense HAT. The ratio of reported malaria cases to reported HAT cases in the same health unit was 133:1, however, the ratio of DALYs was 3:1. The age productive function curve had a close correspondence with the HAT case distribution, and HAT cases occupied more patient admission time in Serere during 1999 than all other infectious diseases other than malaria. The DALY estimate for HAT in Serere shows that the burden is much greater

  4. Interaction between Trypanosoma brucei and Haemonchus ...

    African Journals Online (AJOL)

    In order to investigate the immunomodulatory influence of concurrent T. brucei and H. contortus infection in West African Dwarf (WAD) goats, 28 infected and 7 uninfected (control) of 8-9 months old male WAD goats were studied. The infected goats were separated into resistant (Class 1) and susceptible (Class 2) Faecal ...

  5. A Protein Complex Map of Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Vahid H Gazestani

    2016-03-01

    Full Text Available The functions of the majority of trypanosomatid-specific proteins are unknown, hindering our understanding of the biology and pathogenesis of Trypanosomatida. While protein-protein interactions are highly informative about protein function, a global map of protein interactions and complexes is still lacking for these important human parasites. Here, benefiting from in-depth biochemical fractionation, we systematically interrogated the co-complex interactions of more than 3354 protein groups in procyclic life stage of Trypanosoma brucei, the protozoan parasite responsible for human African trypanosomiasis. Using a rigorous methodology, our analysis led to identification of 128 high-confidence complexes encompassing 716 protein groups, including 635 protein groups that lacked experimental annotation. These complexes correlate well with known pathways as well as for proteins co-expressed across the T. brucei life cycle, and provide potential functions for a large number of previously uncharacterized proteins. We validated the functions of several novel proteins associated with the RNA-editing machinery, identifying a candidate potentially involved in the mitochondrial post-transcriptional regulation of T. brucei. Our data provide an unprecedented view of the protein complex map of T. brucei, and serve as a reliable resource for further characterization of trypanosomatid proteins. The presented results in this study are available at: www.TrypsNetDB.org.

  6. Genetic control of resistance to Trypanosoma brucei brucei infection in mice.

    Directory of Open Access Journals (Sweden)

    Matyáš Síma

    2011-06-01

    Full Text Available Trypanosoma brucei brucei infects livestock, with severe effects in horses and dogs. Mouse strains differ greatly in susceptibility to this parasite. However, no genes controlling these differences were mapped.We studied the genetic control of survival after T. b. brucei infection using recombinant congenic (RC strains, which have a high mapping power. Each RC strain of BALB/c-c-STS/A (CcS/Dem series contains a different random subset of 12.5% genes from the parental "donor" strain STS/A and 87.5% genes from the "background" strain BALB/c. Although BALB/c and STS/A mice are similarly susceptible to T. b. brucei, the RC strain CcS-11 is more susceptible than either of them. We analyzed genetics of survival in T. b. brucei-infected F(2 hybrids between BALB/c and CcS-11. CcS-11 strain carries STS-derived segments on eight chromosomes. They were genotyped in the F(2 hybrid mice and their linkage with survival was tested by analysis of variance.We mapped four Tbbr (Trypanosoma brucei brucei response loci that influence survival after T. b. brucei infection. Tbbr1 (chromosome 3 and Tbbr2 (chromosome 12 have effects on survival independent of inter-genic interactions (main effects. Tbbr3 (chromosome 7 influences survival in interaction with Tbbr4 (chromosome 19. Tbbr2 is located on a segment 2.15 Mb short that contains only 26 genes.This study presents the first identification of chromosomal loci controlling susceptibility to T. b. brucei infection. While mapping in F(2 hybrids of inbred strains usually has a precision of 40-80 Mb, in RC strains we mapped Tbbr2 to a 2.15 Mb segment containing only 26 genes, which will enable an effective search for the candidate gene. Definition of susceptibility genes will improve the understanding of pathways and genetic diversity underlying the disease and may result in new strategies to overcome the active subversion of the immune system by T. b. brucei.

  7. Essential Assembly Factor Rpf2 Forms Novel Interactions within the 5S RNP in Trypanosoma brucei.

    Science.gov (United States)

    Kamina, Anyango D; Jaremko, Daniel; Christen, Linda; Williams, Noreen

    2017-01-01

    Ribosome biogenesis is a highly complex and conserved cellular process that is responsible for making ribosomes. During this process, there are several assembly steps that function as regulators to ensure proper ribosome formation. One of these steps is the assembly of the 5S ribonucleoprotein particle (5S RNP) in the central protuberance of the 60S ribosomal subunit. In eukaryotes, the 5S RNP is composed of 5S rRNA, ribosomal proteins L5 and L11, and assembly factors Rpf2 and Rrs1. Our laboratory previously showed that in Trypanosoma brucei, the 5S RNP is composed of 5S rRNA, L5, and trypanosome-specific RNA binding proteins P34 and P37. In this study, we characterize an additional component of the 5S RNP, the T. brucei homolog of Rpf2. This is the first study to functionally characterize interactions mediated by Rpf2 in an organism other than fungi. T. brucei Rpf2 (TbRpf2) was identified from tandem affinity purification using extracts prepared from protein A-tobacco etch virus (TEV)-protein C (PTP)-tagged L5, P34, and P37 cell lines, followed by mass spectrometry analysis. We characterized the binding interactions between TbRpf2 and the previously characterized members of the T. brucei 5S RNP. Our studies show that TbRpf2 mediates conserved binding interactions with 5S rRNA and L5 and that TbRpf2 also interacts with trypanosome-specific proteins P34 and P37. We performed RNA interference (RNAi) knockdown of TbRpf2 and showed that this protein is essential for the survival of the parasites and is critical for proper ribosome formation. These studies provide new insights into a critical checkpoint in the ribosome biogenesis pathway in T. brucei. IMPORTANCETrypanosoma brucei is the parasitic protozoan that causes African sleeping sickness. Ribosome assembly is essential for the survival of this parasite through the different host environments it encounters during its life cycle. The assembly of the 5S ribonucleoprotein particle (5S RNP) functions as one of the

  8. Trypanosoma brucei: two steps to spread out from Africa.

    Science.gov (United States)

    Lun, Zhao-Rong; Lai, De-Hua; Li, Feng-Jun; Lukes, Julius; Ayala, Francisco J

    2010-09-01

    Trypanosoma brucei equiperdum and Trypanosoma brucei evansi are typically considered separate species, although a recent study suggested that these organisms can be classified as subspecies of Trypanosoma brucei, which we also favor. Here we present a scenario that attempts to explain the continuing evolution of the dyskinetoplastic and akinetoplastic strains, as a consequence of loss of selective pressure(s) leading to the loss of kinetoplast DNA. Copyright 2010 Elsevier Ltd. All rights reserved.

  9. Identification of Trypanosoma evansi, Trypanosoma equiperdum and Trypanosoma brucei brucei using repetitive DNA probes.

    Science.gov (United States)

    Zhang, Z Q; Baltz, T

    1994-06-01

    The phylogenetic relatedness of 15 stocks of Trypanosoma evansi, three stocks of Trypanosoma equiperdum and one stock of Trypanosoma brucei brucei was determined using Southern blot analysis of restriction enzyme digested DNA, probed with two repetitive DNA sequences from T. b. brucei. A dendrogram derived by cluster analysis of restriction fragment length polymorphism (RFLP) revealed three groups of related stocks. Group 1 included 14 stocks of T. evansi and one stock of T. equiperdum. Group 2 included two stocks of T. equiperdum and one stock of T. evansi. Group 3 included the one stock of T. brucei brucei. Group 2 is more closely related to Group 3 than Group 1, by analysis of the banding patterns. Further analysis of the T. evansi in Group 1 revealed that the patterns of isolates from different provinces in China were identical, but differed from T. evansi isolated from Africa, South America and the Philippines. These results provide insight into the origins of T. evansi and suggest that RFLP may be a useful means of distinguishing closely related trypanosomes.

  10. (Berenil(B)) in the Treatment of Experimental Trypanosoma brucei ...

    African Journals Online (AJOL)

    Dr Olaleye

    Animal welfare was observed in accordance with. International guidelines for the use of laboratory animals for biomedical research (EC, 1996). Trypanosomes: Trypanosoma brucei brucei (Federe strain) obtained from NITR, Vom, was used and the parasites were maintained by serial passages in rats. One millilitre of.

  11. The Effect of Garlic Extracts on Experimental Trypanosoma brucei ...

    African Journals Online (AJOL)

    The anti-trypanosomal effect of aqueous and methanolic extracts of garlic were studied in Trypanosoma brucei brucei infected rabbits. With the establishment of infection, parasitaemia, anaemia, leucopenia, neutropenia and lymphocytosis developed. There was decrease in total serum protein, albumin and increase in ...

  12. Pathogenicity of Trypanosoma brucei in African giant rats ...

    African Journals Online (AJOL)

    Pathogenicity of Trypanosoma brucei in African giant rats ( Cricetomys gambianus , Water House) ... The course of trypanosomosis was investigated over a period of two weeks in six African giant rats (Cricetomys gambianus) experimentally infected with Trypanosoma brucei. Six other rats served as uninfected control.

  13. ATG24 Represses Autophagy and Differentiation and Is Essential for Homeostasy of the Flagellar Pocket in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Ana Brennand

    Full Text Available We have previously identified homologs for nearly half of the approximately 30 known yeast Atg's in the genome database of the human sleeping sickness parasite Trypanosoma brucei. So far, only a few of these homologs have their role in autophagy experimentally confirmed. Among the candidates was the ortholog of Atg24 that is involved in pexophagy in yeast. In T. brucei, the peroxisome-like organelles named glycosomes harbor core metabolic processes, especially glycolysis. In the autotrophic yeast, autophagy is essential for adaptation to different nutritional environments by participating in the renewal of the peroxisome population. We hypothesized that autophagic turnover of the parasite's glycosomes plays a role in differentiation during its life cycle, which demands adaptation to different host environments and associated dramatic changes in nutritional conditions. We therefore characterized T. brucei ATG24, the T. brucei ortholog of yeast Atg24 and mammalian SNX4, and found it to have a regulatory role in autophagy and differentiation as well as endocytic trafficking. ATG24 partially localized on endocytic membranes where it was recruited via PI3-kinase III/VPS34. ATG24 silencing severely impaired receptor-mediated endocytosis of transferrin, but not adsorptive uptake of a lectin, and caused a major enlargement of the flagellar pocket. ATG24 silencing approximately doubled the number of autophagosomes, suggesting a role in repressing autophagy, and strongly accelerated differentiation, in accordance with a role of autophagy in parasite differentiation. Overexpression of the two isoforms of T. brucei ATG8 fused to GFP slowed down differentiation, possibly by a dominant-negative effect. This was overcome by ATG24 depletion, further supporting its regulatory role.

  14. Trypanosoma evansi is alike to Trypanosoma brucei brucei in the subcellular localisation of glycolytic enzymes

    Directory of Open Access Journals (Sweden)

    S Andrea Moreno

    2015-06-01

    Full Text Available Trypanosoma evansi, which causes surra, is descended from Trypanosoma brucei brucei, which causes nagana. Although both parasites are presumed to be metabolically similar, insufficient knowledge of T. evansi precludes a full comparison. Herein, we provide the first report on the subcellular localisation of the glycolytic enzymes in T. evansi, which is a alike to that of the bloodstream form (BSF of T. b. brucei: (i fructose-bisphosphate aldolase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH, hexokinase, phosphofructokinase, glucose-6-phosphate isomerase, phosphoglycerate kinase, triosephosphate isomerase (glycolytic enzymes and glycerol-3-phosphate dehydrogenase (a glycolysis-auxiliary enzyme in glycosomes, (ii enolase, phosphoglycerate mutase, pyruvate kinase (glycolytic enzymes and a GAPDH isoenzyme in the cytosol, (iii malate dehydrogenase in cytosol and (iv glucose-6-phosphate dehydrogenase in both glycosomes and the cytosol. Specific enzymatic activities also suggest that T. evansi is alike to the BSF of T. b. brucei in glycolytic flux, which is much faster than the pentose phosphate pathway flux, and in the involvement of cytosolic GAPDH in the NAD+/NADH balance. These similarities were expected based on the close phylogenetic relationship of both parasites.

  15. CHARACTERIZATION AND ANTIPARASITIC ACTIVITY OF BENZOPHENONE THIOSEMICARBAZONES ON Trypanosoma brucei brucei

    Directory of Open Access Journals (Sweden)

    Georges C. Accrombessi

    2011-02-01

    Full Text Available The structure of four synthesized thiosemicarbazones, substituted or not, of benzophenone has been confirmed by spectrometrical analysis IR, NMR 1H and 13C. Their anti-trypanosomal activities were evaluated on Trypanosoma brucei brucei. Among these compounds, benzophenone 4 phenyl-3-thiosemicarbazone 4 has the highest activity with the half-inhibitory concentration (IC50 = 8.48 micromolar (µM. Benzophenone 4-methyl-3-thiosemicarbazone 3 and benzophenone thiosemicarbazone 1 showed moderate anti-trypanosomal activity with IC50 values equal to 23.27 µM and 67.17 µM respectively. Benzophenone 2 methyl-3-thiosemicarbazone 2 showed no activity up to IC50 = 371.74 µM.

  16. 2018-02-23T03:04:41Z https://www.ajol.info/index.php/all/oai oai:ojs ...

    African Journals Online (AJOL)

    Gambian trypanosomosis; Trypanosoma brucei gambiense; animal reservoir hosts; biotechnologies Gambian trypanosomosis (Sleeping Sickness) is a complex and debilitating disease of man. For many years the disease has been ravaging in several parts of sub-saharan Africa despite decades of therapeutic control.

  17. Lipid-drug conjugate nanoparticles of the hydrophilic drug diminazene-cytotoxicity testing and mouse serum adsorption

    NARCIS (Netherlands)

    Olbrich, C.; Gessner, A.; Schroder, W.; Kayser, Oliver; Muller, R.H.

    2004-01-01

    Sleeping sickness is a widely distributed disease in great parts of Africa. It is caused by Trypanosoma brucei gambiense and rhodiense, transmitted by the Tse-Tse fly. After a hemolymphatic stage, the parasites enter the central nervous system where they cannot be reached by hydrophilic drugs. To

  18. Nifurtimox-eflornithine combination therapy for second-stage gambiense human African trypanosomiasis: Médecins Sans Frontières experience in the Democratic Republic of the Congo.

    Science.gov (United States)

    Alirol, Emilie; Schrumpf, David; Amici Heradi, Josué; Riedel, Andrea; de Patoul, Catherine; Quere, Michel; Chappuis, François

    2013-01-01

    Existing diagnostic and treatment tools for human African trypanosomiasis (HAT) are limited. The recent development of nifurtimox-eflornithine combination therapy (NECT) has brought new hopes for patients in the second stage. While NECT has been rolled out in most endemic countries, safety data are scarce and derive only from clinical trials. The World Health Organization (WHO) coordinates a pharmacovigilance program to collect additional data on NECT safety and efficacy. We report here the results of 18 months of experience of NECT use in treatment centers run by Médecins Sans Frontières in the Democratic Republic of the Congo (DRC). This cohort study included 684 second-stage HAT patients (including 120 children) treated with NECT in Doruma and Dingila hospitals, northeastern DRC, between January 2010 and June 2011. All treatment-emergent adverse events (AEs) were recorded and graded according to the Common Terminology Criteria for Adverse Events version 3.0. Safety and efficacy data were retrieved from the WHO pharmacovigilance forms and from Epitryps, a program monitoring database. Eighty-six percent of the patients experienced at least 1 AE during treatment. On average, children experienced fewer AEs than adults. Most AEs were mild (37.9%) or moderate (54.7%). Severe AEs included vomiting (n = 32), dizziness (n = 16), headache (n = 11), and convulsions (n = 11). The in-hospital case fatality rate was low (0.15%) and relapses were rare (n = 14). In comparison with previous treatments, NECT was effective, safe, and well tolerated in nontrial settings in DRC, further supporting the roll-out of NECT as first-line treatment in second-stage Trypanosoma brucei gambiense HAT. Tolerance was particularly good in children.

  19. Mechanisms Mediating Antigenic Variation in Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Rudenko Gloria

    1999-01-01

    Full Text Available Antigenic variation in Trypanosoma brucei is a highly sophisticated survival strategy involving switching between the transcription of one of an estimated thousand variant surface glycoprotein (VSG genes. Switching involves either transcriptional control, resulting in switching between different VSG expression sites; or DNA rearrangement events slotting previously inactive VSG genes into an active VSG expression site. In recent years, considerable progress has been made in techniques allowing us to genetically modify infective bloodstream form trypanosomes. This is allowing us to reengineer VSG expression sites, and look at the effect on the mechanisms subsequently used for antigenic variation. We can now begin a dissection of a highly complicated survival strategy mediated by many different mechanisms operating simultaneously.

  20. Combinations of alkaloids affecting different molecular targets with the saponin digitonin can synergistically enhance trypanocidal activity against Trypanosoma brucei brucei

    National Research Council Canada - National Science Library

    Krstin, Sonja; Peixoto, Herbenya Silva; Wink, Michael

    2015-01-01

    .... In this study, the potential synergism of mutual combinations of bioactive alkaloids and alkaloids with a membrane-active steroidal saponin, digitonin, was explored with regard to their effect on T. b. brucei...

  1. Cytofluorograf detection of Plasmodium yoelii, Trypanosoma gambiense, and Trypanosoma equiperdum by laser excited fluorescence of stained rodent blood.

    Science.gov (United States)

    Jackson, P R; Winkler, D G; Kimzey, S L; Fisher, F M

    1977-08-01

    Samples of rat blood infected with Plasmodium yoelii (3% parasitized erythrocytes), Trypanosoma gambiense, or Trypanosoma equiperdum (greater than 50 trypanosomes per microscope field at 400 X) were fixed with 0.5% glutaraldehyde in phosphate buffered saline, then stained with acridine orange (AO) at 10(-4), 10(-5), or 10(-6) M for 0 to 15 min at 5 C or 25 C and/or ethidium bromide (EB) at 0.05 mg/ml for 20 min at 25 C. Stained cells were analyzed with a laser Cytofluorograf (Bio/Physics Systems, Inc.) to determine if parasites could be detected and differentiated from blood cells by their fluorescent characteristics. Samples of uninfected rat blood with and without leukocytes and P. yoelii-infected blood without leukocytes were treated similarly. In addition, suspensions of T. gambiense and T. equiperdum without all blood cells were stained with AO or EB and analyzed with the Cytofluorograf, as were mixed suspensions of both trypanosome species. EB- but not AO-stained P. yoelii-infected erythrocytes had fluorescent characteristics different from most blood cells. Neither AO- nor EB-stained T. gambiense or T. equiperdum could be differentiated from host blood cells or from each other. The results are discussed with respect to the use of laser flow systems in the detection and analysis of bloodstream dwelling protozoan parasites.

  2. Regulation and spatial organization of PCNA in Trypanosoma brucei

    Energy Technology Data Exchange (ETDEWEB)

    Kaufmann, Doris; Gassen, Alwine [University of Munich (LMU), Department Biology I, Genetics, Grosshaderner Str. 2-4, 82152 Martinsried (Germany); Maiser, Andreas; Leonhardt, Heinrich [University of Munich (LMU), Department Biology II, Grosshaderner Str. 2-4, 82152 Martinsried (Germany); Janzen, Christian J., E-mail: christian.janzen@uni-wuerzburg.de [University of Munich (LMU), Department Biology I, Genetics, Grosshaderner Str. 2-4, 82152 Martinsried (Germany)

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer Characterization of the proliferating cell nuclear antigen in Trypanosoma brucei (TbPCNA). Black-Right-Pointing-Pointer TbPCNA is a suitable marker to detect replication in T. brucei. Black-Right-Pointing-Pointer TbPCNA distribution and regulation is different compared to closely related parasites T. cruzi and Leishmania donovani. -- Abstract: As in most eukaryotic cells, replication is regulated by a conserved group of proteins in the early-diverged parasite Trypanosoma brucei. Only a few components of the replication machinery have been described in this parasite and regulation, sub-nuclear localization and timing of replication are not well understood. We characterized the proliferating cell nuclear antigen in T. brucei (TbPCNA) to establish a spatial and temporal marker for replication. Interestingly, PCNA distribution and regulation is different compared to the closely related parasites Trypanosoma cruzi and Leishmania donovani. TbPCNA foci are clearly detectable during S phase of the cell cycle but in contrast to T. cruzi they are not preferentially located at the nuclear periphery. Furthermore, PCNA seems to be degraded when cells enter G2 phase in T. brucei suggesting different modes of replication regulation or functions of PCNA in these closely related eukaryotes.

  3. Evaluation of In Vitro Activity of Essential Oils against Trypanosoma brucei brucei and Trypanosoma evansi

    Directory of Open Access Journals (Sweden)

    Nathan Habila

    2010-01-01

    Full Text Available Essential oils (EOs from Cymbopogon citratus (CC, Eucalyptus citriodora (EC, Eucalyptus camaldulensis (ED, and Citrus sinensis (CS were obtained by hydrodistillation process. The EOs were evaluated in vitro for activity against Trypanosoma brucei brucei (Tbb and Trypanosoma evansi (T. evansi. The EOs were found to possess antitrypanosomal activity in vitro in a dose-dependent pattern in a short period of time. The drop in number of parasite over time was achieved doses of 0.4 g/ml, 0.2 g/mL, and 0.1 g/mL for all the EOs. The concentration of 0.4 g/mL CC was more potent at 3 minutes and 2 minutes for Tbb and T. evansi, respectively. The GC-MS analysis of the EOs revealed presence of Cyclobutane (96.09% in CS, 6-octenal (77.11% in EC, Eucalyptol (75% in ED, and Citral (38.32% in CC among several other organic compounds. The results are discussed in relation to trypanosome chemotherapy.

  4. Nucleoside analysis of DNA from Trypanosoma brucei and Trypanosoma equiperdum.

    Science.gov (United States)

    Crozatier, M; De Brij, R J; Den Engelse, L; Johnson, P J; Borst, P

    1988-11-01

    We have digested trypanosome DNA with a combination of pancreatic DNase I, nuclease P1 and bovine alkaline phosphatase and fractionated the resulting nucleosides on a Supelcosil LC-18-S column by high pressure liquid chromatography. We find less than 0.1% unusual nucleosides, both in Trypanosoma brucei and in a Trypanosoma equiperdum stock, in contrast to a previous report of an unusual nucleoside replacing dC at 1.3% of total nucleosides in T. equiperdum. Our results agree with previous suggestions that the modification of inactive telomeric expression sites for variant-specific surface glycoprotein genes in T. brucei only affects a very small fraction of the total DNA.

  5. Nitroheterocyclic drug resistance mechanisms in Trypanosoma brucei.

    Science.gov (United States)

    Wyllie, Susan; Foth, Bernardo J; Kelner, Anna; Sokolova, Antoaneta Y; Berriman, Matthew; Fairlamb, Alan H

    2016-03-01

    The objective of this study was to identify the mechanisms of resistance to nifurtimox and fexinidazole in African trypanosomes. Bloodstream-form Trypanosoma brucei were selected for resistance to nifurtimox and fexinidazole by stepwise exposure to increasing drug concentrations. Clones were subjected to WGS to identify putative resistance genes. Transgenic parasites modulating expression of genes of interest were generated and drug susceptibility phenotypes determined. Nifurtimox-resistant (NfxR) and fexinidazole-resistant (FxR) parasites shared reciprocal cross-resistance suggestive of a common mechanism of action. Previously, a type I nitroreductase (NTR) has been implicated in nitro drug activation. WGS of resistant clones revealed that NfxR parasites had lost >100 kb from one copy of chromosome 7, rendering them hemizygous for NTR as well as over 30 other genes. FxR parasites retained both copies of NTR, but lost >70 kb downstream of one NTR allele, decreasing NTR transcription by half. A single knockout line of NTR displayed 1.6- and 1.9-fold resistance to nifurtimox and fexinidazole, respectively. Since NfxR and FxR parasites are ∼6- and 20-fold resistant to nifurtimox and fexinidazole, respectively, additional factors must be involved. Overexpression and knockout studies ruled out a role for a putative oxidoreductase (Tb927.7.7410) and a hypothetical gene (Tb927.1.1050), previously identified in a genome-scale RNAi screen. NTR was confirmed as a key resistance determinant, either by loss of one gene copy or loss of gene expression. Further work is required to identify which of the many dozens of SNPs identified in the drug-resistant cell lines contribute to the overall resistance phenotype. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

  6. Effects of Morinda lucida leaf extract on Trypanosoma brucei brucei infection in mice.

    Science.gov (United States)

    Asuzu, I U; Chineme, C N

    1990-10-01

    The dried leaves of Morinda lucida were extracted with 50% methanol and the extract was recovered in a 9.7% w/w yield. Acute toxicity tests were performed in mice and the intraperitoneal LD50 of the extract was 2000 mg/kg. The extract induced purgation in mice from the first hour after oral administration and reached its peak between the third and fourth hour. The purgation was not dose-dependent. M. lucida leaf extract i.p. significantly suppressed the level of parasitemia after Trypanosoma brucei infection in mice. Suppression of existing parasitemia appeared dose-dependent with 1000 mg/kg i.p. producing the maximum effect. The best trypanocidal activity was obtained when treatment with M. lucida extract commenced simultaneously with trypanosome inoculation.

  7. Monitoring the Progress towards the Elimination of Gambiense Human African Trypanosomiasis.

    Directory of Open Access Journals (Sweden)

    Pere P Simarro

    Full Text Available Over the last few years, momentum has gathered around the feasibility and opportunity of eliminating gambiense human African trypanosomiasis (g-HAT. Under the leadership of the World Health Organization (WHO, a large coalition of stakeholders is now committed to achieving this goal. A roadmap has been laid out, and indicators and milestones have been defined to monitor the progress of the elimination of g-HAT as a public health problem by 2020. Subsequently, a more ambitious objective was set for 2030: to stop disease transmission. This paper provides a situational update to 2012 for a number of indicators of elimination: number of cases annually reported, geographic distribution of the disease and areas and populations at different levels of risk.Comparing the 5-year periods 2003-2007 and 2008-2012, the area at high or very high risk of g-HAT shrank by 60%, while the area at moderate risk decreased by 22%. These are the areas where g-HAT is still to be considered a public health problem (i.e. > 1 HAT reported case per 10,000 people per annum. This contraction of at-risk areas corresponds to a reduction of 57% for the population at high or very high risk (from 4.1 to 1.8 million, and 20% for moderate risk (from 14.0 to 11.3 million.Improved data completeness and accuracy of the Atlas of HAT enhanced our capacity to monitor the progress towards the elimination of g-HAT. The trends in the selected indicators suggest that, in recent years, progress has been steady and in line with the elimination goal laid out in the WHO roadmap on neglected tropical diseases.

  8. ( Nigella sativa ) oil on Trypanosoma brucei -infected rats

    African Journals Online (AJOL)

    The effect of black seed oil (Nigella sativa oil) on parasitaemia, some serum and liver enzymes as well as some haematological parameters in Trypanosoma brucei-infected rats were investigated. The results show there was low parasitaemia and extension of life span of rats from 12 days of the infected untreated (control) ...

  9. Roles of triosephosphate isomerase and aerobic metabolism in Trypanosoma brucei.

    NARCIS (Netherlands)

    Helfert, S.; Estevez, A.M.; Bakker, B.M.; Michels, P.A.M.; Clayton, C.

    2001-01-01

    Kinetoplastid protozoa compartmentalize the first seven enzymes of glycolysis and two enzymes of glycerol metabolism in a microbody, the glycosome. While in its mammalian host, Trypanosoma brucei depends entirely on glucose for ATP generation. Under aerobic conditions, most of the glucose is

  10. Role of cytokines in Trypanosoma brucei-induced anaemia: A ...

    African Journals Online (AJOL)

    the blood-brain barrier. The subspecies Trypanosoma brucei rhodesiense in eastern and southern Africa generally causes a more acute form of ... The persistence of anaemia beyond the initial wave of parasitaemia (after which low numbers of parasites are in circulation) indicates that anaemia may be directly induced.

  11. Trypanocidal action of bisphosphonium salts through a mitochondrial target in bloodstream form Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Abdulsalam A.M. Alkhaldi

    2016-04-01

    Full Text Available Lipophilic bisphosphonium salts are among the most promising antiprotozoal leads currently under investigation. As part of their preclinical evaluation we here report on their mode of action against African trypanosomes, the etiological agents of sleeping sickness. The bisphosphonium compounds CD38 and AHI-9 exhibited rapid inhibition of Trypanosoma brucei growth, apparently the result of cell cycle arrest that blocked the replication of mitochondrial DNA, contained in the kinetoplast, thereby preventing the initiation of S-phase. Incubation with either compound led to a rapid reduction in mitochondrial membrane potential, and ATP levels decreased by approximately 50% within 1 h. Between 4 and 8 h, cellular calcium levels increased, consistent with release from the depolarized mitochondria. Within the mitochondria, the Succinate Dehydrogenase complex (SDH was investigated as a target for bisphosphonium salts, but while its subunit 1 (SDH1 was present at low levels in the bloodstream form trypanosomes, the assembled complex was hardly detectable. RNAi knockdown of the SDH1 subunit produced no growth phenotype, either in bloodstream or in the procyclic (insect forms and we conclude that in trypanosomes SDH is not the target for bisphosphonium salts. Instead, the compounds inhibited ATP production in intact mitochondria, as well as the purified F1 ATPase, to a level that was similar to 1 mM azide. Co-incubation with azide and bisphosphonium compounds did not inhibit ATPase activity more than either product alone. The results show that, in T. brucei, bisphosphonium compounds do not principally act on succinate dehydrogenase but on the mitochondrial FoF1 ATPase.

  12. Trypanocidal action of bisphosphonium salts through a mitochondrial target in bloodstream form Trypanosoma brucei

    Science.gov (United States)

    Alkhaldi, Abdulsalam A.M.; Martinek, Jan; Panicucci, Brian; Dardonville, Christophe; Zíková, Alena; de Koning, Harry P.

    2015-01-01

    Lipophilic bisphosphonium salts are among the most promising antiprotozoal leads currently under investigation. As part of their preclinical evaluation we here report on their mode of action against African trypanosomes, the etiological agents of sleeping sickness. The bisphosphonium compounds CD38 and AHI-9 exhibited rapid inhibition of Trypanosoma brucei growth, apparently the result of cell cycle arrest that blocked the replication of mitochondrial DNA, contained in the kinetoplast, thereby preventing the initiation of S-phase. Incubation with either compound led to a rapid reduction in mitochondrial membrane potential, and ATP levels decreased by approximately 50% within 1 h. Between 4 and 8 h, cellular calcium levels increased, consistent with release from the depolarized mitochondria. Within the mitochondria, the Succinate Dehydrogenase complex (SDH) was investigated as a target for bisphosphonium salts, but while its subunit 1 (SDH1) was present at low levels in the bloodstream form trypanosomes, the assembled complex was hardly detectable. RNAi knockdown of the SDH1 subunit produced no growth phenotype, either in bloodstream or in the procyclic (insect) forms and we conclude that in trypanosomes SDH is not the target for bisphosphonium salts. Instead, the compounds inhibited ATP production in intact mitochondria, as well as the purified F1 ATPase, to a level that was similar to 1 mM azide. Co-incubation with azide and bisphosphonium compounds did not inhibit ATPase activity more than either product alone. The results show that, in T. brucei, bisphosphonium compounds do not principally act on succinate dehydrogenase but on the mitochondrial FoF1 ATPase. PMID:27054061

  13. Protein functional links in Trypanosoma brucei, identified by gene fusion analysis

    Directory of Open Access Journals (Sweden)

    Trimpalis Philip

    2011-07-01

    Full Text Available Abstract Background Domain or gene fusion analysis is a bioinformatics method for detecting gene fusions in one organism by comparing its genome to that of other organisms. The occurrence of gene fusions suggests that the two original genes that participated in the fusion are functionally linked, i.e. their gene products interact either as part of a multi-subunit protein complex, or in a metabolic pathway. Gene fusion analysis has been used to identify protein functional links in prokaryotes as well as in eukaryotic model organisms, such as yeast and Drosophila. Results In this study we have extended this approach to include a number of recently sequenced protists, four of which are pathogenic, to identify fusion linked proteins in Trypanosoma brucei, the causative agent of African sleeping sickness. We have also examined the evolution of the gene fusion events identified, to determine whether they can be attributed to fusion or fission, by looking at the conservation of the fused genes and of the individual component genes across the major eukaryotic and prokaryotic lineages. We find relatively limited occurrence of gene fusions/fissions within the protist lineages examined. Our results point to two trypanosome-specific gene fissions, which have recently been experimentally confirmed, one fusion involving proteins involved in the same metabolic pathway, as well as two novel putative functional links between fusion-linked protein pairs. Conclusions This is the first study of protein functional links in T. brucei identified by gene fusion analysis. We have used strict thresholds and only discuss results which are highly likely to be genuine and which either have already been or can be experimentally verified. We discuss the possible impact of the identification of these novel putative protein-protein interactions, to the development of new trypanosome therapeutic drugs.

  14. A co-evolutionary arms race: trypanosomes shaping the human genome, humans shaping the trypanosome genome.

    Science.gov (United States)

    Capewell, Paul; Cooper, Anneli; Clucas, Caroline; Weir, William; Macleod, Annette

    2015-02-01

    Trypanosoma brucei is the causative agent of African sleeping sickness in humans and one of several pathogens that cause the related veterinary disease Nagana. A complex co-evolution has occurred between these parasites and primates that led to the emergence of trypanosome-specific defences and counter-measures. The first line of defence in humans and several other catarrhine primates is the trypanolytic protein apolipoprotein-L1 (APOL1) found within two serum protein complexes, trypanosome lytic factor 1 and 2 (TLF-1 and TLF-2). Two sub-species of T. brucei have evolved specific mechanisms to overcome this innate resistance, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. In T. b. rhodesiense, the presence of the serum resistance associated (SRA) gene, a truncated variable surface glycoprotein (VSG), is sufficient to confer resistance to lysis. The resistance mechanism of T. b. gambiense is more complex, involving multiple components: reduction in binding affinity of a receptor for TLF, increased cysteine protease activity and the presence of the truncated VSG, T. b. gambiense-specific glycoprotein (TgsGP). In a striking example of co-evolution, evidence is emerging that primates are responding to challenge by T. b. gambiense and T. b. rhodesiense, with several populations of humans and primates displaying resistance to infection by these two sub-species.

  15. In Silico Prediction and Experimental Evaluation of Furanoheliangolide Sesquiterpene Lactones as Potent Agents against Trypanosoma brucei rhodesiense

    Science.gov (United States)

    Da Costa, Fernando B.; Lopes, Norberto P.; Kaiser, Marcel; Brun, Reto

    2014-01-01

    As a continuation of our earlier study on the in vitro antiprotozoal activity of 40 natural sesquiterpene lactones (STLs), we extended the set of tested compounds from our laboratories to 59. On the basis of this extended data set, further enriched by literature data for 10 compounds tested under the same conditions, our quantitative structure-activity relationship (QSAR) analyses for activity against T. brucei rhodesiense (etiologic agent of human African trypanosomiasis, or sleeping sickness) were continued, and the QSAR model thus obtained with 69 structures was used to predict the activity of a virtual library of 1,750 STL structures. As a major result from these calculations, furanoheliangolide-type compounds, a subclass of STLs hitherto untested against T. brucei rhodesiense, were predicted to have an exceptionally high level of in vitro activity. Four representative compounds of this type, goyazensolide, 4,5-dihydro-2′,3′-epoxy-15-deoxygoyazensolide, budlein A, and 4,15-isoatriplicolide tiglate, were therefore tested. They displayed 50% inhibitory concentrations (IC50s) of 0.07, 0.20, 0.07, and 0.015 μM, respectively, so that the in silico prediction was experimentally confirmed. 4,15-Isoatriplicolide tiglate is the most potent STL against T. b. rhodesiense found. Furanoheliangolide STLs were thus identified as interesting leads against this parasite which deserve more detailed investigations. PMID:24165182

  16. Trypanosoma brucei mitochondrial respiratome: Composition and organization in procyclic form

    KAUST Repository

    Acestor, Nathalie

    2011-05-24

    The mitochondrial respiratory chain is comprised of four different protein complexes (I-IV), which are responsible for electron transport and generation of proton gradient in the mitochondrial intermembrane space. This proton gradient is then used by F oF 1-ATP synthase (complex V) to produce ATP by oxidative phosphorylation. In this study, the respiratory complexes I, II, and III were affinity purified from Trypanosoma brucei procyclic form cells and their composition was determined by mass spectrometry. The results along with those that we previously reported for complexes IV and V showed that the respiratome of Trypanosoma is divergent because many of its proteins are unique to this group of organisms. The studies also identified two mitochondrial subunit proteins of respiratory complex IV that are encoded by edited RNAs. Proteomics data from analyses of complexes purified using numerous tagged component proteins in each of the five complexes were used to generate the first predicted protein-protein interaction network of the Trypanosoma brucei respiratory chain. These results provide the first comprehensive insight into the unique composition of the respiratory complexes in Trypanosoma brucei, an early diverged eukaryotic pathogen. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Crystal structure of arginine methyltransferase 6 from Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Chongyuan Wang

    Full Text Available Arginine methylation plays vital roles in the cellular functions of the protozoan Trypanosoma brucei. The T. brucei arginine methyltransferase 6 (TbPRMT6 is a type I arginine methyltransferase homologous to human PRMT6. In this study, we report the crystal structures of apo-TbPRMT6 and its complex with the reaction product S-adenosyl-homocysteine (SAH. The structure of apo-TbPRMT6 displays several features that are different from those of type I PRMTs that were structurally characterized previously, including four stretches of insertion, the absence of strand β15, and a distinct dimerization arm. The comparison of the apo-TbPRMT6 and SAH-TbPRMT6 structures revealed the fine rearrangements in the active site upon SAH binding. The isothermal titration calorimetry results demonstrated that SAH binding greatly increases the affinity of TbPRMT6 to a substrate peptide derived from bovine histone H4. The western blotting and mass spectrometry results revealed that TbPRMT6 methylates bovine histone H4 tail at arginine 3 but cannot methylate several T. brucei histone tails. In summary, our results highlight the structural differences between TbPRMT6 and other type I PRMTs and reveal that the active site rearrangement upon SAH binding is important for the substrate binding of TbPRMT6.

  18. Effect of diminazene aceturate, levamisole and vitamin C combination therapy in rats experimentally infected with Trypanosoma brucei brucei.

    Science.gov (United States)

    Chekwube, Adieme Ijeoma; Onyema, Ezeh Ikenna; Ikenna, Ugochukwu Emmanuel; Ezeokonkwo, Romanus Chukwuduruo

    2014-06-01

    To investigate the effect of diminazene aceturate (DA) alone or in combination with either levamisole and/or Vitamin C in albino rats experimentally infected with Trypanosoma brucei brucei. Thirty adult male albino rats, randomly assigned into 6 groups (A-F) of 5 rats each were used. They were either infected with 1×10(6) trypanosomes intraperitoneally (groups A-E) or uninfected (group F). The different groups were treated respectively as follows: group A-with 3.5 mg/kg DA; group B-3.5 mg/kg DA and 7.5 mg/kg levamisole; group C-3.5 mg/kg DA and 100 mg/kg vitamin C; and group D-3.5 mg/kg DA and 7.5 mg/kg levamisole and 100 mg/kg vitamin C. Group E was left untreated. Parameters assessed include: rectal temperature, body weight changes, packed cell volume (PCV), Haemoglobin concentration (Hb), total leucocyte count (TLC) differential leucocyte count (DLC), parasitaemia, clinical signs and survivability. Average pre-patent period of 5 days was recorded. Parasites in the blood were cleared in all treated groups (A-D) within 48 hours post treatment (PT). Untreated rats in group E died between 25 and 32 days post infection (PI). Relapse was not recorded in all the treated groups (A-D). The initial reduction in PCV, Hb, TLC and increases in rectal temperature following infection were reversed by the treatments. The rats that received drug combinations (groups B, C and D) showed faster and higher recovery rates than the uninfected control and group A. Levamisole and/or Vitamin C combination with DA were more effective in the treatment of rats infected with Trypanosoma brucei brucei. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  19. Adding tsetse control to medical activities contributes to decreasing transmission of sleeping sickness in the Mandoul focus (Chad).

    Science.gov (United States)

    Mahamat, Mahamat Hissene; Peka, Mallaye; Rayaisse, Jean-Baptiste; Rock, Kat S; Toko, Mahamat Abdelrahim; Darnas, Justin; Brahim, Guihini Mollo; Alkatib, Ali Bachar; Yoni, Wilfrid; Tirados, Inaki; Courtin, Fabrice; Brand, Samuel P C; Nersy, Cyrus; Alfaroukh, Idriss Oumar; Torr, Steve J; Lehane, Mike J; Solano, Philippe

    2017-07-01

    Gambian sleeping sickness or HAT (human African trypanosomiasis) is a neglected tropical disease caused by Trypanosoma brucei gambiense transmitted by riverine species of tsetse. A global programme aims to eliminate the disease as a public health problem by 2020 and stop transmission by 2030. In the South of Chad, the Mandoul area is a persistent focus of Gambian sleeping sickness where around 100 HAT cases were still diagnosed and treated annually until 2013. Pre-2014, control of HAT relied solely on case detection and treatment, which lead to a gradual decrease in the number of cases of HAT due to annual screening of the population. Because of the persistence of transmission and detection of new cases, we assessed whether the addition of vector control to case detection and treatment could further reduce transmission and consequently, reduce annual incidence of HAT in Mandoul. In particular, we investigated the impact of deploying 'tiny targets' which attract and kill tsetse. Before tsetse control commenced, a census of the human population was conducted and their settlements mapped. A pre-intervention survey of tsetse distribution and abundance was implemented in November 2013 and 2600 targets were deployed in the riverine habitats of tsetse in early 2014, 2015 and 2016. Impact on tsetse and on the incidence of sleeping sickness was assessed through nine tsetse monitoring surveys and four medical surveys of the human population in 2014 and 2015. Mathematical modelling was used to assess the relative impact of tsetse control on incidence compared to active and passive screening. The census indicated that a population of 38674 inhabitants lived in the vicinity of the Mandoul focus. Within this focus in November 2013, the vector is Glossina fuscipes fuscipes and the mean catch of tsetse from traps was 0.7 flies/trap/day (range, 0-26). The catch of tsetse from 44 sentinel biconical traps declined after target deployment with only five tsetse being caught in nine

  20. Adding tsetse control to medical activities contributes to decreasing transmission of sleeping sickness in the Mandoul focus (Chad.

    Directory of Open Access Journals (Sweden)

    Mahamat Hissene Mahamat

    2017-07-01

    Full Text Available Gambian sleeping sickness or HAT (human African trypanosomiasis is a neglected tropical disease caused by Trypanosoma brucei gambiense transmitted by riverine species of tsetse. A global programme aims to eliminate the disease as a public health problem by 2020 and stop transmission by 2030. In the South of Chad, the Mandoul area is a persistent focus of Gambian sleeping sickness where around 100 HAT cases were still diagnosed and treated annually until 2013. Pre-2014, control of HAT relied solely on case detection and treatment, which lead to a gradual decrease in the number of cases of HAT due to annual screening of the population.Because of the persistence of transmission and detection of new cases, we assessed whether the addition of vector control to case detection and treatment could further reduce transmission and consequently, reduce annual incidence of HAT in Mandoul. In particular, we investigated the impact of deploying 'tiny targets' which attract and kill tsetse. Before tsetse control commenced, a census of the human population was conducted and their settlements mapped. A pre-intervention survey of tsetse distribution and abundance was implemented in November 2013 and 2600 targets were deployed in the riverine habitats of tsetse in early 2014, 2015 and 2016. Impact on tsetse and on the incidence of sleeping sickness was assessed through nine tsetse monitoring surveys and four medical surveys of the human population in 2014 and 2015. Mathematical modelling was used to assess the relative impact of tsetse control on incidence compared to active and passive screening.The census indicated that a population of 38674 inhabitants lived in the vicinity of the Mandoul focus. Within this focus in November 2013, the vector is Glossina fuscipes fuscipes and the mean catch of tsetse from traps was 0.7 flies/trap/day (range, 0-26. The catch of tsetse from 44 sentinel biconical traps declined after target deployment with only five tsetse being

  1. Steroid Alkaloids from Holarrhena africana with Strong Activity against Trypanosoma brucei rhodesiense.

    Science.gov (United States)

    Nnadi, Charles Okeke; Nwodo, Ngozi Justina; Kaiser, Marcel; Brun, Reto; Schmidt, Thomas J

    2017-07-06

    In our continued search for natural compounds with activity against Trypanosoma brucei, causative agent of human African trypanosomiasis (HAT, "sleeping sickness"), we have investigated extracts from the leaves and bark of the West African Holarrhenaafricana (syn. Holarrhena floribunda; Apocynaceae). The extracts and their alkaloid-enriched fractions displayed promising in vitro activity against bloodstream forms of T. brucei rhodesiense (Tbr; East African HAT). Bioactivity-guided chromatographic fractionation of the alkaloid-rich fractions resulted in the isolation of 17 steroid alkaloids, one nitrogen-free steroid and one alkaloid-like non-steroid. Impressive activities (IC50 in µM) against Tbr were recorded for 3β-holaphyllamine (0.40 ± 0.28), 3α-holaphyllamine (0.37 ± 0.16), 3β-dihydroholaphyllamine (0.67 ± 0.03), N-methylholaphyllamine (0.08 ± 0.01), conessimine (0.17 ± 0.08), conessine (0.42 ± 0.09), isoconessimine (0.17 ± 0.11) and holarrhesine (0.12 ± 0.08) with selectivity indices ranging from 13 to 302. Based on comparison of the structures of this congeneric series of steroid alkaloids and their activities, structure-activity relationships (SARs) could be established. It was found that a basic amino group at position C-3 of the pregnane or pregn-5-ene steroid nucleus is required for a significant anti-trypanosomal activity. The mono-methylated amino group at C-3 represents an optimum for activity. ∆(5,6) unsaturation slightly increased the activity while hydrolysis of C-12β ester derivatives led to a loss of activity. An additional amino group at C-20 engaged in a pyrrolidine ring closed towards C-18 significantly increased the selectivity index of the compounds. Our findings provide useful empirical data for further development of steroid alkaloids as a novel class of anti-trypanosomal compounds which represent a promising starting point towards new drugs to combat human African trypanosomiasis.

  2. Steroid Alkaloids from Holarrhena africana with Strong Activity against Trypanosoma brucei rhodesiense

    Directory of Open Access Journals (Sweden)

    Charles Okeke Nnadi

    2017-07-01

    Full Text Available In our continued search for natural compounds with activity against Trypanosoma brucei, causative agent of human African trypanosomiasis (HAT, “sleeping sickness”, we have investigated extracts from the leaves and bark of the West African Holarrhena africana (syn. Holarrhena floribunda; Apocynaceae. The extracts and their alkaloid-enriched fractions displayed promising in vitro activity against bloodstream forms of T. brucei rhodesiense (Tbr; East African HAT. Bioactivity-guided chromatographic fractionation of the alkaloid-rich fractions resulted in the isolation of 17 steroid alkaloids, one nitrogen-free steroid and one alkaloid-like non-steroid. Impressive activities (IC50 in µM against Tbr were recorded for 3β-holaphyllamine (0.40 ± 0.28, 3α-holaphyllamine (0.37 ± 0.16, 3β-dihydroholaphyllamine (0.67 ± 0.03, N-methylholaphyllamine (0.08 ± 0.01, conessimine (0.17 ± 0.08, conessine (0.42 ± 0.09, isoconessimine (0.17 ± 0.11 and holarrhesine (0.12 ± 0.08 with selectivity indices ranging from 13 to 302. Based on comparison of the structures of this congeneric series of steroid alkaloids and their activities, structure-activity relationships (SARs could be established. It was found that a basic amino group at position C-3 of the pregnane or pregn-5-ene steroid nucleus is required for a significant anti-trypanosomal activity. The mono-methylated amino group at C-3 represents an optimum for activity. ∆5,6 unsaturation slightly increased the activity while hydrolysis of C-12β ester derivatives led to a loss of activity. An additional amino group at C-20 engaged in a pyrrolidine ring closed towards C-18 significantly increased the selectivity index of the compounds. Our findings provide useful empirical data for further development of steroid alkaloids as a novel class of anti-trypanosomal compounds which represent a promising starting point towards new drugs to combat human African trypanosomiasis.

  3. Rab23 is a flagellar protein in Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Field Mark C

    2011-06-01

    Full Text Available Abstract Background Rab small GTPases are important mediators of membrane transport, and orthologues frequently retain similar locations and functions, even between highly divergent taxa. In metazoan organisms Rab23 is an important negative regulator of Sonic hedgehog signaling and is crucial for correct development and differentiation of cellular lineages by virtue of an involvement in ciliary recycling. Previously, we reported that Trypanosoma brucei Rab23 localized to the nuclear envelope 1, which is clearly inconsistent with the mammalian location and function. As T. brucei is unicellular the potential that Rab23 has no role in cell signaling was possible. Here we sought to further investigate the role(s of Rab23 in T. brucei to determine if Rab23 was an example of a Rab protein with divergent function in distinct taxa. Methods/major findings The taxonomic distribution of Rab23 was examined and compared with the presence of flagella/cilia in representative taxa. Despite evidence for considerable secondary loss, we found a clear correlation between a conventional flagellar structure and the presence of a Rab23 orthologue in the genome. By epitope-tagging, Rab23 was localized and found to be present at the flagellum throughout the cell cycle. However, RNAi knockdown did not result in a flagellar defect, suggesting that Rab23 is not required for construction or maintenance of the flagellum. Conclusions The location of Rab23 at the flagellum is conserved between mammals and trypanosomes and the Rab23 gene is restricted to flagellated organisms. These data may suggest the presence of a Rab23-mediated signaling mechanism in trypanosomes.

  4. Minimum Information Loss Based Multi-kernel Learning for Flagellar Protein Recognition in Trypanosoma Brucei

    KAUST Repository

    Wang, Jim Jing-Yan

    2014-12-01

    Trypanosma brucei (T. Brucei) is an important pathogen agent of African trypanosomiasis. The flagellum is an essential and multifunctional organelle of T. Brucei, thus it is very important to recognize the flagellar proteins from T. Brucei proteins for the purposes of both biological research and drug design. In this paper, we investigate computationally recognizing flagellar proteins in T. Brucei by pattern recognition methods. It is argued that an optimal decision function can be obtained as the difference of probability functions of flagella protein and the non-flagellar protein for the purpose of flagella protein recognition. We propose to learn a multi-kernel classification function to approximate this optimal decision function, by minimizing the information loss of such approximation which is measured by the Kull back-Leibler (KL) divergence. An iterative multi-kernel classifier learning algorithm is developed to minimize the KL divergence for the problem of T. Brucei flagella protein recognition, experiments show its advantage over other T. Brucei flagellar protein recognition and multi-kernel learning methods. © 2014 IEEE.

  5. Telomeric expression sites are highly conserved in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Christiane Hertz-Fowler

    Full Text Available Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs. The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology.

  6. Spliced leader RNA silencing (SLS - a programmed cell death pathway in Trypanosoma brucei that is induced upon ER stress

    Directory of Open Access Journals (Sweden)

    Michaeli Shulamit

    2012-05-01

    Full Text Available Abstract Trypanosoma brucei is the causative agent of African sleeping sickness. The parasite cycles between its insect (procyclic form and mammalian hosts (bloodstream form. Trypanosomes lack conventional transcription regulation, and their genes are transcribed in polycistronic units that are processed by trans-splicing and polyadenylation. In trans-splicing, which is essential for processing of each mRNA, an exon, the spliced leader (SL is added to all mRNAs from a small RNA, the SL RNA. Trypanosomes lack the machinery for the unfolded protein response (UPR, which in other eukaryotes is induced under endoplasmic reticulum (ER stress. Trypanosomes respond to such stress by changing the stability of mRNAs, which are essential for coping with the stress. However, under severe ER stress that is induced by blocking translocation of proteins to the ER, treatment of cells with chemicals that induce misfolding in the ER, or extreme pH, trypanosomes elicit the spliced leader silencing (SLS pathway. In SLS, the transcription of the SL RNA gene is extinguished, and tSNAP42, a specific SL RNA transcription factor, fails to bind to its cognate promoter. SLS leads to complete shut-off of trans-splicing. In this review, I discuss the UPR in mammals and compare it to the ER stress response in T. brucei leading to SLS. I summarize the evidence supporting the notion that SLS is a programmed cell death (PCD pathway that is utilized by the parasites to substitute for the apoptosis observed in higher eukaryotes under prolonged ER stress. I present the hypothesis that SLS evolved to expedite the death process, and rapidly remove from the population unfit parasites that, by elimination via SLS, cause minimal damage to the parasite population.

  7. Structural Characterization of CYP51 from Trypanosoma cruzi and Trypanosoma brucei Bound to the Antifungal Drugs Posaconazole and Fluconazole

    Science.gov (United States)

    Chen, Chiung-Kuang; Leung, Siegfried S. F.; Guilbert, Christophe; Jacobson, Matthew P.; McKerrow, James H.; Podust, Larissa M.

    2010-01-01

    Background Chagas Disease is the leading cause of heart failure in Latin America. Current drug therapy is limited by issues of both efficacy and severe side effects. Trypansoma cruzi, the protozoan agent of Chagas Disease, is closely related to two other major global pathogens, Leishmania spp., responsible for leishmaniasis, and Trypansoma brucei, the causative agent of African Sleeping Sickness. Both T. cruzi and Leishmania parasites have an essential requirement for ergosterol, and are thus vulnerable to inhibitors of sterol 14α-demethylase (CYP51), which catalyzes the conversion of lanosterol to ergosterol. Clinically employed anti-fungal azoles inhibit ergosterol biosynthesis in fungi, and specific azoles are also effective against both Trypanosoma and Leishmania parasites. However, modification of azoles to enhance efficacy and circumvent potential drug resistance has been problematic for both parasitic and fungal infections due to the lack of structural insights into drug binding. Methodology/Principal Findings We have determined the crystal structures for CYP51 from T. cruzi (resolutions of 2.35 Å and 2.27 Å), and from the related pathogen T. brucei (resolutions of 2.7 Å and 2.6 Å), co-crystallized with the antifungal drugs fluconazole and posaconazole. Remarkably, both drugs adopt multiple conformations when binding the target. The fluconazole 2,4-difluorophenyl ring flips 180° depending on the H-bonding interactions with the BC-loop. The terminus of the long functional tail group of posaconazole is bound loosely in the mouth of the hydrophobic substrate binding tunnel, suggesting that the major contribution of the tail to drug efficacy is for pharmacokinetics rather than in interactions with the target. Conclusions/Significance The structures provide new insights into binding of azoles to CYP51 and mechanisms of potential drug resistance. Our studies define in structural detail the CYP51 therapeutic target in T. cruzi, and offer a starting point for

  8. Antitrypanosomal effect of methanolic extract of Zingiber officinale (ginger on Trypanosoma brucei brucei-infected Wistar mice

    Directory of Open Access Journals (Sweden)

    P. I. Kobo

    2014-10-01

    Full Text Available Aim: The study was carried out to determine the in vivo antitrypanosomal effect of methanolic extract of Zingiber officinale (ginger in Trypanosoma brucei brucei-infected mice. Materials and Methods: Twenty-five mice were randomly allocated into five groups of five animals each. Group I and II were given Tween 80 (1 ml/kg and diminazene aceturate (3.5 mg/kg to serve as untreated and treated controls, respectively. Groups III-V received the extract at 200, 400 and 800 mg/kg body weight, respectively. All treatments were given for 6 consecutive days and through the oral route. The mean body weight, mean survival period and daily level of parasitaemia were evaluated. Results: Acute toxicity showed the extract to be relatively safe. There was an insignificant increase in body weight and survival rate of mice treated with the extract. The level of parasitaemia in the extract treated groups was decreased. Conclusion: This study shows the in vivo potential of methanolic extract of Z. officinale in the treatment of trypanosomiasis.

  9. Sleep Apnea

    Science.gov (United States)

    ... repeated awakenings associated with sleep apnea make normal, restorative sleep impossible. People with sleep apnea often experience ... et al. Sleep breathing disorders. In: Principles and Practice of Sleep Medicine. 5th ed. St. Louis, Mo.: ...

  10. In or out? On the tightness of glycosomal compartmentalizatin of metabolites and enzymes in Trypanosoma brucei.

    NARCIS (Netherlands)

    Haanstra, J.R.; Bakker, B.M.; Michels, P.A.M.

    2014-01-01

    Trypanosomatids sequester large parts of glucose metabolism inside specialised peroxisomes, called glycosomes. Many studies have shown that correct glycosomal compartmentalization of glycolytic enzymes is essential for bloodstream-form Trypanosoma brucei. The recent finding of pore-forming

  11. 1H, 13C and 15N resonance assignment of Urm1 from Trypanosoma brucei.

    Science.gov (United States)

    Zhang, Wen; Ding, Husheng; Zhang, Jiahai; Tu, Xiaoming

    2008-06-01

    Urm1 (ubiquitin-related modifier), involved in diverse biological processes in yeast, is proved to be a "molecular fossil" in ubiquitin superfamily. Here we report the resonance assignment of Urm1 from Trypanosoma brucei.

  12. A Flagellar Pocket Membrane Fraction from Trypanosoma brucei rhodesiense: Immunogold Localization and Nonvariant Immunoprotection

    Science.gov (United States)

    1988-01-01

    membrane components. specific glycoproteins from Trypanosoma equiperdum variants. Exp. Parasitol. 64:1-11. FEBS Lett. 82:93-96. 20. Melton, D. W., D. S...Fraction from Trypanosoma brucei rhodesiense: Immunogold Localization and Nonvariant Immunoprotection JOHN G. OLENICK,* RUTH WOLFF,’ ROBERT K. NAUMAN...obtained for each of three distinct variable antigenic types (VATs) of a serodeme of Trypanosoma brucei rhodesiense Wellcome strain. Products of

  13. Characterization of Trypanosoma brucei dihydroorotate dehydrogenase as a possible drug target; structural, kinetic and RNAi studies.

    Science.gov (United States)

    Arakaki, Tracy L; Buckner, Frederick S; Gillespie, J Robert; Malmquist, Nicholas A; Phillips, Margaret A; Kalyuzhniy, Oleksandr; Luft, Joseph R; Detitta, George T; Verlinde, Christophe L M J; Van Voorhis, Wesley C; Hol, Wim G J; Merritt, Ethan A

    2008-04-01

    Nucleotide biosynthesis pathways have been reported to be essential in some protozoan pathogens. Hence, we evaluated the essentiality of one enzyme in the pyrimidine biosynthetic pathway, dihydroorotate dehydrogenase (DHODH) from the eukaryotic parasite Trypanosoma brucei through gene knockdown studies. RNAi knockdown of DHODH expression in bloodstream form T. brucei did not inhibit growth in normal medium, but profoundly retarded growth in pyrimidine-depleted media or in the presence of the known pyrimidine uptake antagonist 5-fluorouracil (5-FU). These results have significant implications for the development of therapeutics to combat T. brucei infection. Specifically, a combination therapy including a T. brucei-specific DHODH inhibitor plus 5-FU may prove to be an effective therapeutic strategy. We also show that this trypanosomal enzyme is inhibited by known inhibitors of bacterial Class 1A DHODH, in distinction to the sensitivity of DHODH from human and other higher eukaryotes. This selectivity is supported by the crystal structure of the T. brucei enzyme, which is reported here at a resolution of 1.95 A. Additional research, guided by the crystal structure described herein, is needed to identify potent inhibitors of T. brucei DHODH.

  14. Technical data of the transcriptomic analysis performed on tsetse fly symbionts, Sodalis glossinidius and Wigglesworthia glossinidia, harbored, respectively by non-infected, Trypanosoma brucei gambiense infected and self-cured Glossina palpalis gambiensis tsetse flies.

    Science.gov (United States)

    Geiger, Anne; Tchicaya, Bernadette; Rihet, Pascal

    2015-06-01

    Microarray is a powerful and cheap method to identify and quantify gene expression in particular in a mix of total RNA extracted from biological samples such as the tsetse fly gut, including several organisms (here, the fly tissue and the intestinal microorganisms). Besides, biostatistics and bioinformatics allow comparing the transcriptomes from samples collected from differently treated flies, and thus to identify and quantify differential expressed genes. Here, we describe in details a whole microarray transcriptome dataset produced from tsetse flies symbionts, Sodalis glossinidius and Wigglesworthia glossinidia. The tsetse fly midguts were sampled at key steps of tsetse fly infection by trypanosomes, 3-day and 10-day sampling times to target differentially expressed genes involved, respectively, in early events associated with trypanosome entry into the midgut and with the establishment of infection; 20 days to target the genes involved in events occurring later in the infection process. We describe in detail the methodology applied for analyzing the microarray data including differential expression as well as functional annotation of the identified symbiont genes. Both the microarray data and design are available at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE48360;http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE48361;http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE55931.

  15. Enhanced passive screening and diagnosis for gambiense human African trypanosomiasis in north-western Uganda - Moving towards elimination.

    Directory of Open Access Journals (Sweden)

    Charles Wamboga

    Full Text Available The incidence of gambiense human African trypanosomiasis (gHAT in Uganda has been declining, from 198 cases in 2008, to only 20 in 2012. Interruption of transmission of the disease by early diagnosis and treatment is core to the control and eventual elimination of gHAT. Until recently, the format of available screening tests had restricted screening and diagnosis to central health facilities (passive screening. We describe a novel strategy that is contributing to elimination of gHAT in Uganda through expansion of passive screening to the entire population at risk.In this strategy, patients who are clinically suspected of having gHAT at primary health facilities are screened using a rapid diagnostic test (RDT, followed by parasitological confirmation at strategically located microscopy centres. For patients who are positive with the RDT and negative by microscopy, blood samples undergo further testing using loop-mediated isothermal amplification (LAMP, a molecular test that detects parasite DNA. LAMP positive patients are considered strong suspects, and are re-evaluated by microscopy. Location and upgrading of facilities to perform microscopy and LAMP was informed by results of georeferencing and characterization of all public healthcare facilities in the 7 gHAT endemic districts in Uganda. Three facilities were upgraded to perform RDTs, microscopy and LAMP, 9 to perform RDTs and microscopy, and 200 to screen patients with RDTs. This reduced the distance that a sick person must travel to be screened for gHAT to a median distance of 2.5km compared to 23km previously. In this strategy, 9 gHAT cases were diagnosed in 2014, and 4 in 2015.This enhanced passive screening strategy for gHAT has enabled full coverage of the population at risk, and is being replicated in other gHAT endemic countries. The improvement in case detection is making elimination of the disease in Uganda an imminent possibility.

  16. Sleep Disorders

    Science.gov (United States)

    ... the day, even if you have had enough sleep? You might have a sleep disorder. The most common kinds are Insomnia - a hard time falling or staying asleep Sleep apnea - breathing interruptions during sleep Restless legs syndrome - ...

  17. Role of centrins 2 and 3 in organelle segregation and cytokinesis in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Angamuthu Selvapandiyan

    Full Text Available Centrins are calcium binding proteins involved in cell division in eukaryotes. Previously, we have shown that depletion of centrin1 in Trypanosoma brucei (T. brucei displayed arrested organelle segregation resulting in loss of cytokinesis. In this study we analyzed the role of T. brucei centrin2 (TbCen2 and T. brucei 3 (TbCen3 in the early events of T. brucei procyclic cell cycle. Both the immunofluorescence assay and electron microscopy showed that TbCen2 and 3-deficient cells were enlarged in size with duplicated basal bodies, multinuclei and new flagella that are detached along the length of the cell body. In both TbCen2 and TbCen3 depleted cells segregation of the organelles i.e. basal bodies, kinetoplast and nucleus was disrupted. Further analysis of the cells with defective organelle segregation identified three different sub configurations of organelle mis-segregations (Type 1-3. In addition, in majority of the TbCen2 depleted cells and in nearly half of the TbCen3 depleted cells, the kinetoplasts were enlarged and undivided. The abnormal segregations ultimately led to aborted cytokinesis and hence affected growth in these cells. Therefore, both centrin2 and 3 are involved in organelle segregation similar to centrin1 as was previously observed. In addition, we identified their role in kinetoplast division which may be also linked to overall mis-segregation.

  18. High-throughput Gene Tagging in Trypanosoma brucei.

    Science.gov (United States)

    Dyer, Philip; Dean, Samuel; Sunter, Jack

    2016-08-12

    Improvements in mass spectrometry, sequencing and bioinformatics have generated large datasets of potentially interesting genes. Tagging these proteins can give insights into their function by determining their localization within the cell and enabling interaction partner identification. We recently published a fast and scalable method to generate Trypanosoma brucei cell lines that express a tagged protein from the endogenous locus. The method was based on a plasmid we generated that, when coupled with long primer PCR, can be used to modify a gene to encode a protein tagged at either terminus. This allows the tagging of dozens of trypanosome proteins in parallel, facilitating the large-scale validation of candidate genes of interest. This system can be used to tag proteins for localization (using a fluorescent protein, epitope tag or electron microscopy tag) or biochemistry (using tags for purification, such as the TAP (tandem affinity purification) tag). Here, we describe a protocol to perform the long primer PCR and the electroporation in 96-well plates, with the recovery and selection of transgenic trypanosomes occurring in 24-well plates. With this workflow, hundreds of proteins can be tagged in parallel; this is an order of magnitude improvement to our previous protocol and genome scale tagging is now possible.

  19. IL-6 is Upregulated in Late-Stage Disease in Monkeys Experimentally Infected with Trypanosoma brucei rhodesiense

    Directory of Open Access Journals (Sweden)

    Dawn Nyawira Maranga

    2013-01-01

    Full Text Available The management of human African trypanosomiasis (HAT is constrained by lack of simple-to-use diagnostic, staging, and treatment tools. The search for novel biomarkers is, therefore, essential in the fight against HAT. The current study aimed at investigating the potential of IL-6 as an adjunct parameter for HAT stage determination in vervet monkey model. Four adult vervet monkeys (Chlorocebus aethiops were experimentally infected with Trypanosoma brucei rhodesiense and treated subcuratively at 28 days after infection (dpi to induce late stage disease. Three noninfected monkeys formed the control group. Cerebrospinal fluid (CSF and blood samples were obtained at weekly intervals and assessed for various biological parameters. A typical HAT-like infection was observed. The late stage was characterized by significant (P<0.05 elevation of CSF IL-6, white blood cell count, and total protein starting 35 dpi with peak levels of these parameters coinciding with relapse parasitaemia. Brain immunohistochemical staining revealed an increase in brain glial fibrillary acidic protein expression indicative of reactive astrogliosis in infected animals which were euthanized in late-stage disease. The elevation of IL-6 in CSF which accompanied other HAT biomarkers indicates onset of parasite neuroinvasion and show potential for use as an adjunct late-stage disease biomarker in the Rhodesian sleeping sickness.

  20. IL-6 is Upregulated in Late-Stage Disease in Monkeys Experimentally Infected with Trypanosoma brucei rhodesiense

    Science.gov (United States)

    Nyawira Maranga, Dawn; Kagira, John Maina; Kinyanjui, Christopher Kariuki; Muturi Karanja, Simon; Wangari Maina, Naomi; Ngotho, Maina

    2013-01-01

    The management of human African trypanosomiasis (HAT) is constrained by lack of simple-to-use diagnostic, staging, and treatment tools. The search for novel biomarkers is, therefore, essential in the fight against HAT. The current study aimed at investigating the potential of IL-6 as an adjunct parameter for HAT stage determination in vervet monkey model. Four adult vervet monkeys (Chlorocebus aethiops) were experimentally infected with Trypanosoma brucei rhodesiense and treated subcuratively at 28 days after infection (dpi) to induce late stage disease. Three noninfected monkeys formed the control group. Cerebrospinal fluid (CSF) and blood samples were obtained at weekly intervals and assessed for various biological parameters. A typical HAT-like infection was observed. The late stage was characterized by significant (P < 0.05) elevation of CSF IL-6, white blood cell count, and total protein starting 35 dpi with peak levels of these parameters coinciding with relapse parasitaemia. Brain immunohistochemical staining revealed an increase in brain glial fibrillary acidic protein expression indicative of reactive astrogliosis in infected animals which were euthanized in late-stage disease. The elevation of IL-6 in CSF which accompanied other HAT biomarkers indicates onset of parasite neuroinvasion and show potential for use as an adjunct late-stage disease biomarker in the Rhodesian sleeping sickness. PMID:24194772

  1. Ligand tunnels in T. brucei and human CYP51: Insights for parasite-specific drug design.

    Science.gov (United States)

    Yu, Xiaofeng; Nandekar, Prajwal; Mustafa, Ghulam; Cojocaru, Vlad; Lepesheva, Galina I; Wade, Rebecca C

    2016-01-01

    Cytochrome P450 sterol 14α-demethylase (CYP51) is an essential enzyme for sterol biosynthesis and a target for anti-parasitic drug design. However, the design of parasite-specific drugs that inhibit parasitic CYP51 without severe side effects remains challenging. The active site of CYP51 is situated in the interior of the protein. Here, we characterize the potential ligand egress routes and mechanisms in Trypanosoma brucei and human CYP51 enzymes. We performed Random Acceleration Molecular Dynamics simulations of the egress of four different ligands from the active site of models of soluble and membrane-bound T. brucei CYP51 and of soluble human CYP51. In the simulations, tunnel 2f, which leads to the membrane, was found to be the predominant ligand egress tunnel for all the ligands studied. Tunnels S, 1 and W, which lead to the cytosol, were also used in T. brucei CYP51, whereas tunnel 1 was the only other tunnel used significantly in human CYP51. The common tunnels found previously in other CYPs were barely used. The ligand egress times were shorter for human than T. brucei CYP51, suggesting lower barriers to ligand passage. Two gating residues, F105 and M460, in T. brucei CYP51 that modulate the opening of tunnels 2f and S were identified. Although the main egress tunnel was the same, differences in the tunnel-lining residues, ligand passage and tunnel usage were found between T. brucei and human CYP51s. The results provide a basis for the design of selective anti-parasitic agents targeting the ligand tunnels. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. International Journal of Health Research

    African Journals Online (AJOL)

    Erah

    Trypanosoma brucei gambiense and. Trypanosoma brucei rhodesiense, and Animal trypanosomiaisis, caused by trypanosoma brucei brucei.. Worldwide ... activity. We report here for the first time that hexane and aqueous extracts of the stem bark of. A. senegalensis cure experimental infection in mice. Methods.

  3. Sleep Quiz

    Science.gov (United States)

    ... the radio up will keep the drowsy driver awake. _____5. Narcolepsy is a sleep disorder marked by " ... disturbed sleep. Sleeping during the day in a dark, quiet bedroom and getting exposure to sufficient bright ...

  4. Arterial blood pressure changes in acute T. brucei infection of dogs ...

    African Journals Online (AJOL)

    The aim of this study is to find out the usefulness of serial arterial blood pressure measurements in predicting severity and outcome of acute Trypanosoma brucei infection in dogs. Twenty adult dogs of mixed sexes and aged between 2 and 5 years were used for this study. The dogs were of good cardiac health and were ...

  5. Biosynthesis of SUMOylated Proteins in Bacteria Using the Trypanosoma brucei Enzymatic System

    Science.gov (United States)

    Iribarren, Paula Ana; Berazategui, María Agustina; Cazzulo, Juan José; Alvarez, Vanina Eder

    2015-01-01

    Post-translational modification with the Small Ubiquitin-like Modifier (SUMO) is conserved in eukaryotic organisms and plays important regulatory roles in proteins affecting diverse cellular processes. In Trypanosoma brucei, member of one of the earliest branches in eukaryotic evolution, SUMO is essential for normal cell cycle progression and is likely to be involved in the epigenetic control of genes crucial for parasite survival, such as those encoding the variant surface glycoproteins. Molecular pathways modulated by SUMO have started to be discovered by proteomic studies; however, characterization of functional consequences is limited to a reduced number of targets. Here we present a bacterial strain engineered to produce SUMOylated proteins, by transferring SUMO from T. brucei together with the enzymes essential for its activation and conjugation. Due to the lack of background in E. coli, this system is useful to express and identify SUMOylated proteins directly in cell lysates by immunoblotting, and SUMOylated targets can be eventually purified for biochemical or structural studies. We applied this strategy to describe the ability of TbSUMO to form chains in vitro and to detect SUMOylation of a model substrate, PCNA both from Saccharomyces cerevisiae and from T. brucei. To further validate targets, we applied an in vitro deconjugation assay using the T. brucei SUMO-specific protease capable to revert the pattern of modification. This system represents a valuable tool for target validation, mutant generation and functional studies of SUMOylated proteins in trypanosomatids. PMID:26258470

  6. Phosphatidylinositol 4-kinase III-beta is required for Golgi maintenance and cytokinesis in Trypanosoma brucei.

    Science.gov (United States)

    Rodgers, Melissa J; Albanesi, Joseph P; Phillips, Margaret A

    2007-07-01

    The parasitic protozoan Trypanosoma brucei contains two type III phosphatidylinositol 4-kinases (alpha and beta). We have cloned the gene encoding the T. brucei type III phosphatidylinositol 4-kinase beta (TbPI4KIII-beta), expressed the protein in COS-7 cells, and confirmed that the protein catalyzes the phosphorylation of phosphatidylinositol. Depletion of TbPI4KIII-beta in procyclic T. brucei by RNA interference (RNAi) resulted in inhibition of cell growth and a distorted cellular morphology. RNAi cells had a distorted Golgi apparatus, and lysosomal and flagellar pocket proteins were mislocalized. Ultrastructural analysis revealed the internal accumulation of a heterogeneous population of vesicles, abnormal positioning of organelles, and a loss of cell polarity. Scanning electron microcopy revealed a twisted phenotype, and dividing cells often exhibited a detached daughter flagellum and lacked a cleavage furrow. Cell cycle analysis confirmed that cells depleted of TbPI4KIII-beta have a postmitotic cytokinesis block that occurs after a single round of mitosis, suggestive of a specific cell cycle block. In summary, TbPI4KIII-beta is an essential protein in procyclic T. brucei, required for maintenance of Golgi structure, protein trafficking, normal cellular shape, and cytokinesis.

  7. Particle-bound enzymes in the bloodstream form of Trypanosoma brucei

    NARCIS (Netherlands)

    Opperdoes, F. R.; Borst, P.; Spits, H.

    1977-01-01

    We have screened the bloodstream form of Trypanosoma brucei for the presence of enzymes that could serve as markers for the microbodies and the highly repressed mitochondrion of this organism. None of seven known microbody enzymes were detected at all, but glycerol-3-phosphate oxidase, ATPase,

  8. Procyclic Trypanosoma brucei do not use Krebs cycle activity for energy generation

    NARCIS (Netherlands)

    Weelden, van S.W.H.; Fast, B.; Vogt, A.; Meer, van der P.; Saas, J.; Hellemond, van J.J.; Tielens, A.G.M.; Boshart, M.

    2003-01-01

    The importance of a functional Krebs cycle for energy generation in the procyclic stage of Trypanosoma brucei was investigated under physiological conditions during logarithmic phase growth of a pleomorphic parasite strain. Wild type procyclic cells and mutants with targeted deletion of the gene

  9. Contribution of glucose transport to the control of the glycolytic flux in Trypanosoma brucei.

    NARCIS (Netherlands)

    Bakker, B.M.; Walsh, M.C.; ter Kuile, B.; Mensonides, F.I.C.; Michels, P.A.M.; Opperdoes, F.R.; Westerhoff, H.V.

    1999-01-01

    The rate of glucose transport across the plasma membrane of the bloodstream form of Trypanosoma brucei was modulated by titration of the hexose transporter with the inhibitor phloretin, and the effect on the glycolytic flux was measured. A rapid glucose uptake assay was developed to measure the

  10. The promoter for a variant surface glycoprotein gene expression site in Trypanosoma brucei

    NARCIS (Netherlands)

    Zomerdijk, J. C.; Ouellette, M.; ten Asbroek, A. L.; Kieft, R.; Bommer, A. M.; Clayton, C. E.; Borst, P.

    1990-01-01

    The variant-specific surface glycoprotein (VSG) gene 221 of Trypanosoma brucei is transcribed as part of a 60 kb expression site (ES). We have identified the promoter controlling this multigene transcription unit by the use of 221 chromosome-enriched DNA libraries and VSG gene 221 expression site

  11. Maf1 is a negative regulator of transcription in Trypanosoma brucei.

    Science.gov (United States)

    Romero-Meza, Gabriela; Vélez-Ramírez, Daniel E; Florencio-Martínez, Luis E; Román-Carraro, Fiordaliso C; Manning-Cela, Rebeca; Hernández-Rivas, Rosaura; Martínez-Calvillo, Santiago

    2017-02-01

    RNA polymerase III (Pol III) produces small RNA molecules that play essential roles in mRNA processing and translation. Maf1, originally described as a negative regulator of Pol III transcription, has been studied from yeast to human. Here we characterized Maf1 in the parasitic protozoa Trypanosoma brucei (TbMaf1), representing the first report to analyse Maf1 in an early-diverged eukaryote. While Maf1 is generally encoded by a single-copy gene, the T. brucei genome contains two almost identical TbMaf1 genes. The TbMaf1 protein has the three conserved sequences and is predicted to fold into a globular structure. Unlike in yeast, TbMaf1 localizes to the nucleus in procyclic forms of T. brucei under normal growth conditions. Cell lines that either downregulate or overexpress TbMaf1 were generated, and growth curve analysis with them suggested that TbMaf1 participates in the regulation of cell growth of T. brucei. Nuclear run-on and chromatin immunoprecipitation analyses demonstrated that TbMaf1 represses Pol III transcription of tRNA and U2 snRNA genes by associating with their promoters. Interestingly, 5S rRNA levels do not change after TbMaf1 ablation or overexpression. Notably, our data also revealed that TbMaf1 regulates Pol I transcription of procyclin gene and Pol II transcription of SL RNA genes. © 2016 John Wiley & Sons Ltd.

  12. Isolation and characterization of kinetoplast DNA from the bloodstream form of Trypanosoma brucei.

    NARCIS (Netherlands)

    A.H. Fairlamb; P.O. Weislogel; J.H.J. Hoeijmakers (Jan); P. Borst (Piet)

    1978-01-01

    textabstractWe have used restriction endonucleases PstI, EcoRI, HapII, HhaI, and S1 nuclease to demonstrate the presence of a large complex component, the maxi-circle, in addition to the major mini-circle component in kinetoplast DNA (kDNA) networks of Trypanosoma brucei (East African

  13. Deletion of the Trypanosoma brucei Superoxide Dismutase Gene sodb1 Increases Sensitivity to Nifurtimox and Benznidazole▿

    Science.gov (United States)

    Prathalingham, S. Radhika; Wilkinson, Shane R.; Horn, David; Kelly, John M.

    2007-01-01

    It has been more than 25 years since it was first reported that nifurtimox and benznidazole promote superoxide production in trypanosomes. However, there has been no direct evidence of an association between the drug-induced free radicals and trypanocidal activity. Here, we identify a superoxide dismutase required to protect Trypanosoma brucei from drug-generated superoxide. PMID:17145786

  14. Deletion of the Trypanosoma brucei superoxide dismutase gene sodb1 increases sensitivity to nifurtimox and benznidazole.

    Science.gov (United States)

    Prathalingham, S Radhika; Wilkinson, Shane R; Horn, David; Kelly, John M

    2007-02-01

    It has been more than 25 years since it was first reported that nifurtimox and benznidazole promote superoxide production in trypanosomes. However, there has been no direct evidence of an association between the drug-induced free radicals and trypanocidal activity. Here, we identify a superoxide dismutase required to protect Trypanosoma brucei from drug-generated superoxide.

  15. Trypanosoma brucei Infection in a herd of sedentary cattle in Danja ...

    African Journals Online (AJOL)

    Trypanosoma brucei Infection in a herd of sedentary cattle in Danja Local Government Area, Katsina State, Northern Nigeria– A possible resurgence of Tsetse flies ... resulted in advocacy for pastoralists to settle down into productive cattle production compared to the nomadic behavior which does not enhance productivity.

  16. Biosynthesis of SUMOylated Proteins in Bacteria Using the Trypanosoma brucei Enzymatic System.

    Directory of Open Access Journals (Sweden)

    Paula Ana Iribarren

    Full Text Available Post-translational modification with the Small Ubiquitin-like Modifier (SUMO is conserved in eukaryotic organisms and plays important regulatory roles in proteins affecting diverse cellular processes. In Trypanosoma brucei, member of one of the earliest branches in eukaryotic evolution, SUMO is essential for normal cell cycle progression and is likely to be involved in the epigenetic control of genes crucial for parasite survival, such as those encoding the variant surface glycoproteins. Molecular pathways modulated by SUMO have started to be discovered by proteomic studies; however, characterization of functional consequences is limited to a reduced number of targets. Here we present a bacterial strain engineered to produce SUMOylated proteins, by transferring SUMO from T. brucei together with the enzymes essential for its activation and conjugation. Due to the lack of background in E. coli, this system is useful to express and identify SUMOylated proteins directly in cell lysates by immunoblotting, and SUMOylated targets can be eventually purified for biochemical or structural studies. We applied this strategy to describe the ability of TbSUMO to form chains in vitro and to detect SUMOylation of a model substrate, PCNA both from Saccharomyces cerevisiae and from T. brucei. To further validate targets, we applied an in vitro deconjugation assay using the T. brucei SUMO-specific protease capable to revert the pattern of modification. This system represents a valuable tool for target validation, mutant generation and functional studies of SUMOylated proteins in trypanosomatids.

  17. BAPTA-AM decreases cellular pH, inhibits acidocalcisome acidification and autophagy in amino acid-starved T. brucei.

    Science.gov (United States)

    Li, Feng-Jun; Tan, Kevin S W; He, Cynthia Y

    2017-04-01

    To investigate the role of Ca2+ signaling in starvation-induced autophagy in Trypanosoma brucei, the causative agent of human African trypanosomiasis, we used cell-permeant Ca2+ chelator BAPTA-AM and cell impermeant chelator EGTA, and examined the potential involvement of several intracellular Ca2+ signaling pathways in T. brucei autophagy. The results showed an unexpected effect of BAPTA-AM in decreasing cellular pH and inhibiting acidocalcisome acidification in starved cells. The implication of these results in the role of Ca2+ signaling and cellular/organellar pH in T. brucei autophagy is discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Sleep Disorders

    DEFF Research Database (Denmark)

    Rahbek Kornum, Birgitte; Mignot, Emmanuel

    2014-01-01

    in these networks create sleep disorders, including rapid eye movement sleep behavior disorder, sleep walking, and narcolepsy. Physiological changes associated with sleep can be imbalanced, resulting in excess movements such as periodic leg movements during sleep or abnormal breathing in obstructive sleep apneas......Mammalian sleep has evolved under the influence of the day-night cycle and in response to reproductive needs, food seeking, and predator avoidance, resulting in circadian (predictive) and homeostatic (reactive) regulation. A molecular clock characterized by transcription/translation feedback loops...... mediates circadian regulation of sleep. Misalignment with the rhythm of the sun results in circadian disorders and jet lag. The molecular basis of homeostatic sleep regulation is mostly unknown. A network of mutually inhibitory brain nuclei regulates sleep states and sleep-wake transitions. Abnormalities...

  19. Understanding chromatin dynamics during antigenic variation in trypanosoma brucei

    OpenAIRE

    Branco, Francisco Maria dos Santos e Silva Aresta, 1985-

    2016-01-01

    Tese de doutoramento, Ciências Biomédicas (Microbiologia e Parasitologia), Universidade de Lisboa, Faculdade de Medicina, 2016 African trypanosomiasis is a disease restricted to sub-Saharian Africa and it assumes two forms: Human African trypanosomiasis (HAT or sleeping sickness) or Animal African trypanosomiasis (AAT or n’gana), both being fatal if untreated. While HAT causes an estimated number of 15000 new cases each year and 70 million people are at risk, AAT causes an enormous economi...

  20. Sleep inertia.

    Science.gov (United States)

    Tassi, Patricia; Muzet, Alain

    2000-08-01

    Sleep inertia is a transitional state of lowered arousal occurring immediately after awakening from sleep and producing a temporary decrement in subsequent performance. Many factors are involved in the characteristics of sleep inertia. The duration of prior sleep can influence the severity of subsequent sleep inertia. Although most studies have focused on sleep inertia after short naps, its effects can be shown after a normal 8-h sleep period. One of the most critical factors is the sleep stage prior to awakening. Abrupt awakening during a slow wave sleep (SWS) episode produces more sleep inertia than awakening in stage 1 or 2, REM sleep being intermediate. Therefore, prior sleep deprivation usually enhances sleep inertia since it increases SWS. There is no direct evidence that sleep inertia exhibits a circadian rhythm. However, it seems that sleep inertia is more intense when awakening occurs near the trough of the core body temperature as compared to its circadian peak. A more controversial issue concerns the time course of sleep inertia. Depending on the studies, it can last from 1 min to 4 h. However, in the absence of major sleep deprivation, the duration of sleep inertia rarely exceeds 30 min. But all these results should be analysed as a function of type of task and dependent variables. Different cognitive functions are probably not sensitive to the same degree to sleep inertia and special attention should be provided to dependent variables as a result of the cognitive processes under review. Finally, sleep disorders represent risk factors which deserve new insight in treatment strategies to counteract the adverse effects of sleep inertia.

  1. Trypanosoma brucei rhodesiense transmitted by a single tsetse fly bite in vervet monkeys as a model of human African trypanosomiasis.

    Directory of Open Access Journals (Sweden)

    John K Thuita

    Full Text Available We have investigated the pathogenicity of tsetse (Glossina pallidipes-transmitted cloned strains of Trypanosoma brucei rhodesiense in vervet monkeys. Tsetse flies were confirmed to have mature trypanosome infections by xenodiagnosis, after which nine monkeys were infected via the bite of a single infected fly. Chancres developed in five of the nine (55.6% monkeys within 4 to 8 days post infection (dpi. All nine individuals were successfully infected, with a median pre-patent period of 4 (range = 4-10 days, indicating that trypanosomes migrated from the site of fly bite to the systemic circulation rapidly and independently of the development of the chancre. The time lag to detection of parasites in cerebrospinal fluid (CSF was a median 16 (range = 8-40 days, marking the onset of central nervous system (CNS, late stage disease. Subsequently, CSF white cell numbers increased above the pre-infection median count of 2 (range = 0-9 cells/microl, with a positive linear association between their numbers and that of CSF trypanosomes. Haematological changes showed that the monkeys experienced an early microcytic-hypochromic anaemia and severe progressive thrombocytopaenia. Despite a 3-fold increase in granulocyte numbers by 4 dpi, leucopaenia occurred early (8 dpi in the monkey infection, determined mainly by reductions in lymphocyte numbers. Terminally, leucocytosis was observed in three of nine (33% individuals. The duration of infection was a median of 68 (range = 22-120 days. Strain and individual differences were observed in the severity of the clinical and clinical pathology findings, with two strains (KETRI 3741 and 3801 producing a more acute disease than the other two (KETRI 3804 and 3928. The study shows that the fly-transmitted model accurately mimics the human disease and is therefore a suitable gateway to understanding human African trypanosomiasis (HAT; sleeping sickness.

  2. Functional and structural insights revealed by molecular dynamics simulations of an essential RNA editing ligase in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Rommie E Amaro

    2007-11-01

    Full Text Available RNA editing ligase 1 (TbREL1 is required for the survival of both the insect and bloodstream forms of Trypanosoma brucei, the parasite responsible for the devastating tropical disease African sleeping sickness. The type of RNA editing that TbREL1 is involved in is unique to the trypanosomes, and no close human homolog is known to exist. In addition, the high-resolution crystal structure revealed several unique features of the active site, making this enzyme a promising target for structure-based drug design. In this work, two 20 ns atomistic molecular dynamics (MD simulations are employed to investigate the dynamics of TbREL1, both with and without the ATP substrate present. The flexibility of the active site, dynamics of conserved residues and crystallized water molecules, and the interactions between TbREL1 and the ATP substrate are investigated and discussed in the context of TbREL1's function. Differences in local and global motion upon ATP binding suggest that two peripheral loops, unique to the trypanosomes, may be involved in interdomain signaling events. Notably, a significant structural rearrangement of the enzyme's active site occurs during the apo simulations, opening an additional cavity adjacent to the ATP binding site that could be exploited in the development of effective inhibitors directed against this protozoan parasite. Finally, ensemble averaged electrostatics calculations over the MD simulations reveal a novel putative RNA binding site, a discovery that has previously eluded scientists. Ultimately, we use the insights gained through the MD simulations to make several predictions and recommendations, which we anticipate will help direct future experimental studies and structure-based drug discovery efforts against this vital enzyme.

  3. Costs Of Using “Tiny Targets” to Control Glossina fuscipes fuscipes, a Vector of Gambiense Sleeping Sickness in Arua District of Uganda

    Science.gov (United States)

    Shaw, Alexandra P. M.; Tirados, Inaki; Mangwiro, Clement T. N.; Esterhuizen, Johan; Lehane, Michael J.; Torr, Stephen J.; Kovacic, Vanja

    2015-01-01

    Introduction To evaluate the relative effectiveness of tsetse control methods, their costs need to be analysed alongside their impact on tsetse populations. Very little has been published on the costs of methods specifically targeting human African trypanosomiasis Methodology/Principal Findings In northern Uganda, a 250 km2 field trial was undertaken using small (0.5 X 0.25 m) insecticide-treated targets (“tiny targets”). Detailed cost recording accompanied every phase of the work. Costs were calculated for this operation as if managed by the Ugandan vector control services: removing purely research components of the work and applying local salaries. This calculation assumed that all resources are fully used, with no spare capacity. The full cost of the operation was assessed at USD 85.4 per km2, of which USD 55.7 or 65.2% were field costs, made up of three component activities (target deployment: 34.5%, trap monitoring: 10.6% and target maintenance: 20.1%). The remaining USD 29.7 or 34.8% of the costs were for preliminary studies and administration (tsetse surveys: 6.0%, sensitisation of local populations: 18.6% and office support: 10.2%). Targets accounted for only 12.9% of the total cost, other important cost components were labour (24.1%) and transport (34.6%). Discussion Comparison with the updated cost of historical HAT vector control projects and recent estimates indicates that this work represents a major reduction in cost levels. This is attributed not just to the low unit cost of tiny targets but also to the organisation of delivery, using local labour with bicycles or motorcycles. Sensitivity analyses were undertaken, investigating key prices and assumptions. It is believed that these costs are generalizable to other HAT foci, although in more remote areas, with denser vegetation and fewer people, costs would increase, as would be the case for other tsetse control techniques. PMID:25811956

  4. Alkaloids Induce Programmed Cell Death in Bloodstream Forms of Trypanosomes (Trypanosoma b. brucei

    Directory of Open Access Journals (Sweden)

    Michael Wink

    2008-10-01

    Full Text Available The potential induction of a programmed cell death (PCD in Trypanosoma b. brucei by 55 alkaloids of the quinoline, quinolizidine, isoquinoline, indole, terpene, tropane, steroid, and piperidine type was studied by measuring DNA fragmentation and changes in mitochondrial membrane potential. For comparison, the induction of apoptosis by the same alkaloids in human leukemia cells (Jurkat APO-S was tested. Several alkaloids of the isoquinoline, quinoline, indole and steroidal type (berberine, chelerythrine, emetine, sanguinarine, quinine, ajmalicine, ergotamine, harmine, vinblastine, vincristine, colchicine, chaconine, demissidine and veratridine induced programmed cell death, whereas quinolizidine, tropane, terpene and piperidine alkaloids were mostly inactive. Effective PCD induction (EC50 below 10 µM was caused in T. brucei by chelerythrine, emetine, sanguinarine, and chaconine. The active alkaloids can be characterized by their general property to inhibit protein biosynthesis, to intercalate DNA, to disturb membrane fluidity or to inhibit microtubule formation.

  5. Differential virulence and tsetse fly transmissibility of Trypanosoma congolense and Trypanosoma brucei strains

    Directory of Open Access Journals (Sweden)

    Purity K. Gitonga

    2017-01-01

    Full Text Available African animal trypanosomiasis causes significant economic losses in sub-Saharan African countries because of livestock mortalities and reduced productivity. Trypanosomes, the causative agents, are transmitted by tsetse flies (Glossina spp.. In the current study, we compared and contrasted the virulence characteristics of five Trypanosoma congolense and Trypanosoma brucei isolates using groups of Swiss white mice (n = 6. We further determined the vectorial capacity of Glossina pallidipes, for each of the trypanosome isolates. Results showed that the overall pre-patent (PP periods were 8.4 ± 0.9 (range, 4–11 and 4.5 ± 0.2 (range, 4–6 for T. congolense and T. brucei isolates, respectively (p < 0.01. Despite the longer mean PP, T. congolense–infected mice exhibited a significantly (p < 0.05 shorter survival time than T. brucei–infected mice, indicating greater virulence. Differences were also noted among the individual isolates with T. congolense KETRI 2909 causing the most acute infection of the entire group with a mean ± standard error survival time of 9 ± 2.1 days. Survival time of infected tsetse flies and the proportion with mature infections at 30 days post-exposure to the infective blood meals varied among isolates, with subacute infection–causing T. congolense EATRO 1829 and chronic infection–causing T. brucei EATRO 2267 isolates showing the highest mature infection rates of 38.5% and 23.1%, respectively. Therefore, our study provides further evidence of occurrence of differences in virulence and transmissibility of eastern African trypanosome strains and has identified two, T. congolense EATRO 1829 and T. brucei EATRO 2267, as suitable for tsetse infectivity and transmissibility experiments.

  6. An Atypical Mitochondrial Carrier That Mediates Drug Action in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Juan P de Macêdo

    2015-05-01

    Full Text Available Elucidating the mechanism of action of trypanocidal compounds is an important step in the development of more efficient drugs against Trypanosoma brucei. In a screening approach using an RNAi library in T. brucei bloodstream forms, we identified a member of the mitochondrial carrier family, TbMCP14, as a prime candidate mediating the action of a group of anti-parasitic choline analogs. Depletion of TbMCP14 by inducible RNAi in both bloodstream and procyclic forms increased resistance of parasites towards the compounds by 7-fold and 3-fold, respectively, compared to uninduced cells. In addition, down-regulation of TbMCP14 protected bloodstream form mitochondria from a drug-induced decrease in mitochondrial membrane potential. Conversely, over-expression of the carrier in procyclic forms increased parasite susceptibility more than 13-fold. Metabolomic analyses of parasites over-expressing TbMCP14 showed increased levels of the proline metabolite, pyrroline-5-carboxylate, suggesting a possible involvement of TbMCP14 in energy production. The generation of TbMCP14 knock-out parasites showed that the carrier is not essential for survival of T. brucei bloodstream forms, but reduced parasite proliferation under standard culture conditions. In contrast, depletion of TbMCP14 in procyclic forms resulted in growth arrest, followed by parasite death. The time point at which parasite proliferation stopped was dependent on the major energy source, i.e. glucose versus proline, in the culture medium. Together with our findings that proline-dependent ATP production in crude mitochondria from TbMCP14-depleted trypanosomes was reduced compared to control mitochondria, the study demonstrates that TbMCP14 is involved in energy production in T. brucei. Since TbMCP14 belongs to a trypanosomatid-specific clade of mitochondrial carrier family proteins showing very poor similarity to mitochondrial carriers of mammals, it may represent an interesting target for drug

  7. Procyclic Trypanosoma brucei do not use Krebs cycle activity for energy generation.

    Science.gov (United States)

    van Weelden, Susanne W H; Fast, Beate; Vogt, Achim; van der Meer, Pieter; Saas, Joachim; van Hellemond, Jaap J; Tielens, Aloysius G M; Boshart, Michael

    2003-04-11

    The importance of a functional Krebs cycle for energy generation in the procyclic stage of Trypanosoma brucei was investigated under physiological conditions during logarithmic phase growth of a pleomorphic parasite strain. Wild type procyclic cells and mutants with targeted deletion of the gene coding for aconitase were derived by synchronous in vitro differentiation from wild type and mutant (Delta aco::NEO/Delta aco::HYG) bloodstream stage parasites, respectively, where aconitase is not expressed and is dispensable. No differences in intracellular levels of glycolytic and Krebs cycle intermediates were found in procyclic wild type and mutant cells, except for citrate that accumulated up to 90-fold in the mutants, confirming the absence of aconitase activity. Surprisingly, deletion of aconitase did not change differentiation nor the growth rate or the intracellular ATP/ADP ratio in those cells. Metabolic studies using radioactively labeled substrates and NMR analysis demonstrated that glucose and proline were not degraded via the Krebs cycle to CO(2). Instead, glucose was degraded to acetate, succinate, and alanine, whereas proline was degraded to succinate. Importantly, there was absolutely no difference in the metabolic products released by wild type and aconitase knockout parasites, and both were for survival strictly dependent on respiration via the mitochondrial electron transport chain. Hence, although the Krebs cycle enzymes are present, procyclic T. brucei do not use Krebs cycle activity for energy generation, but the mitochondrial respiratory chain is essential for survival and growth. We therefore propose a revised model of the energy metabolism of procyclic T. brucei.

  8. Mapping of branch sites in trans-spliced pre-mRNAs of Trypanosoma brucei.

    Science.gov (United States)

    Patzelt, E; Perry, K L; Agabian, N

    1989-01-01

    The process of trans splicing is essential to the maturation of all mRNAs in the Trypanosomatidae, a family of protozoan parasites, and to specific mRNAs in several species of nematode. In Trypanosoma brucei, a 39-nucleotide (nt) leader sequence originating from a small, 139-nt donor RNA (the spliced leader [SL] RNA) is spliced to the 5' end of mRNAs. An intermediate in this trans-splicing process is a Y structure which contains the 3' 100 nt of the SL RNA covalently linked to the pre-mRNA via a 2'-5' phosphodiester bond at the branch point residue. We mapped the branch points in T. brucei alpha- and beta-tubulin pre-mRNAs. The primary branch acceptors for the alpha- and beta-tubulins are 44 and 56 nt upstream of the 3' splice sites, respectively, and are A residues. Minor branch acceptors were detected 42 and 49 nt upstream of the alpha-tubulin splice site and 58 nt upstream of the splice site in beta-tubulin. The regions surrounding these branch points lack homology to the consensus sequences determined for mammalian cells and yeasts; there is also no conservation among the sequences themselves. Thus, the identified sequences suggest that the mechanism of branch point recognition in T. brucei differs from the mechanism of recognition by U2 RNA that has been proposed for other eucaryotes. Images PMID:2479824

  9. The inositol pyrophosphate synthesis pathway in Trypanosoma brucei is linked to polyphosphate synthesis in acidocalcisomes.

    Science.gov (United States)

    Cordeiro, Ciro D; Saiardi, Adolfo; Docampo, Roberto

    2017-10-01

    Inositol pyrophosphates are novel signaling molecules possessing high-energy pyrophosphate bonds and involved in a number of biological functions. Here, we report the correct identification and characterization of the kinases involved in the inositol pyrophosphate biosynthetic pathway in Trypanosoma brucei: inositol polyphosphate multikinase (TbIPMK), inositol pentakisphosphate 2-kinase (TbIP5K) and inositol hexakisphosphate kinase (TbIP6K). TbIP5K and TbIP6K were not identifiable by sequence alone and their activities were validated by enzymatic assays with the recombinant proteins or by their complementation of yeast mutants. We also analyzed T. brucei extracts for the presence of inositol phosphates using polyacrylamide gel electrophoresis and high-performance liquid chromatography. Interestingly, we could detect inositol phosphate (IP), inositol 4,5-bisphosphate (IP2 ), inositol 1,4,5-trisphosphate (IP3 ), and inositol hexakisphosphate (IP6 ) in T. brucei different stages. Bloodstream forms unable to produce inositol pyrophosphates, due to downregulation of TbIPMK expression by conditional knockout, have reduced levels of polyphosphate and altered acidocalcisomes. Our study links the inositol pyrophosphate pathway to the synthesis of polyphosphate in acidocalcisomes, and may lead to better understanding of these organisms and provide new targets for drug discovery. © 2017 John Wiley & Sons Ltd.

  10. NLP is a novel transcription regulator involved in VSG expression site control in Trypanosoma brucei.

    Science.gov (United States)

    Narayanan, Mani Shankar; Kushwaha, Manish; Ersfeld, Klaus; Fullbrook, Alexander; Stanne, Tara M; Rudenko, Gloria

    2011-03-01

    Trypanosoma brucei mono-allelically expresses one of approximately 1500 variant surface glycoprotein (VSG) genes while multiplying in the mammalian bloodstream. The active VSG is transcribed by RNA polymerase I in one of approximately 15 telomeric VSG expression sites (ESs). T. brucei is unusual in controlling gene expression predominantly post-transcriptionally, and how ESs are mono-allelically controlled remains a mystery. Here we identify a novel transcription regulator, which resembles a nucleoplasmin-like protein (NLP) with an AT-hook motif. NLP is key for ES control in bloodstream form T. brucei, as NLP knockdown results in 45- to 65-fold derepression of the silent VSG221 ES. NLP is also involved in repression of transcription in the inactive VSG Basic Copy arrays, minichromosomes and procyclin loci. NLP is shown to be enriched on the 177- and 50-bp simple sequence repeats, the non-transcribed regions around rDNA and procyclin, and both active and silent ESs. Blocking NLP synthesis leads to downregulation of the active ES, indicating that NLP plays a role in regulating appropriate levels of transcription of ESs in both their active and silent state. Discovery of the unusual transcription regulator NLP provides new insight into the factors that are critical for ES control.

  11. NIMA-related kinase TbNRKC is involved in basal body separation in Trypanosoma brucei.

    Science.gov (United States)

    Pradel, Lydie C; Bonhivers, Mélanie; Landrein, Nicolas; Robinson, Derrick R

    2006-05-01

    The NIMA-related kinase 2 (NEK 2) has important cell cycle functions related to centriole integrity and splitting. Trypanosoma brucei does not possess centrioles, however, cytokinesis is coupled to basal body separation events. Here we report the first functional characterisation of a T. brucei basal body-cytoskeletal NIMA-related kinase (NRK) protein, TbNRKC. The TbNRKC kinase domain has high amino acid identity with the human NEK1 kinase domain (50%) but also shares 42% identity with human NEK2. TbNRKC is expressed in bloodstream and procyclic cells and functions as a bona fide kinase in vitro. Remarkably, RNAi knockdown of TbNRKC and overexpression of kinase-dead TbNRKC in procyclic forms induces the accumulation of cells with four basal bodies, whereas overexpression of active protein produces supernumary basal bodies and blocks cytokinesis. TbNRKC is located on mature and immature basal bodies and is the first T. brucei NRK to be found associated with the basal body cytokinesis pathway.

  12. Obstructive Sleep Apnea

    Science.gov (United States)

    ... to find out more. Obstructive Sleep Apnea Obstructive Sleep Apnea Obstructive sleep apnea (OSA) is a serious ... to find out more. Obstructive Sleep Apnea Obstructive Sleep Apnea Obstructive sleep apnea (OSA) is a serious ...

  13. Sleep Apnea

    Science.gov (United States)

    Sleep apnea is a common disorder that causes your breathing to stop or get very shallow. Breathing ... an hour. The most common type is obstructive sleep apnea. It causes your airway to collapse or ...

  14. Sleep Quiz

    Science.gov (United States)

    ... to ensure that research results lead to health benefits. It works towards this goal by educating health care professionals about sleep disorders and research findings, and translating sleep health ...

  15. A Pre-clinical Animal Model of Trypanosoma brucei Infection Demonstrating Cardiac Dysfunction.

    Directory of Open Access Journals (Sweden)

    Charlotte S McCarroll

    2015-05-01

    Full Text Available African trypanosomiasis (AT, caused by Trypanosoma brucei species, results in both neurological and cardiac dysfunction and can be fatal if untreated. Research on the pathogenesis and treatment of the disease has centred to date on the characteristic neurological symptoms, whereas cardiac dysfunction (e.g. ventricular arrhythmias in AT remains largely unstudied. Animal models of AT demonstrating cardiac dysfunction similar to that described in field cases of AT are critically required to transform our understanding of AT-induced cardiac pathophysiology and identify future treatment strategies. We have previously shown that T. brucei can interact with heart muscle cells (cardiomyocytes to induce ventricular arrhythmias in ex vivo adult rat hearts. However, it is unknown whether the arrhythmias observed ex vivo are also present during in vivo infection in experimental animal models. Here we show for the first time the characterisation of ventricular arrhythmias in vivo in two animal models of AT infection using electrocardiographic (ECG monitoring. The first model utilised a commonly used monomorphic laboratory strain, Trypanosoma brucei brucei Lister 427, whilst the second model used a pleomorphic laboratory strain, T. b. brucei TREU 927, which demonstrates a similar chronic infection profile to clinical cases. The frequency of ventricular arrhythmias and heart rate (HR was significantly increased at the endpoint of infection in the TREU 927 infection model, but not in the Lister 427 infection model. At the end of infection, hearts from both models were isolated and Langendorff perfused ex vivo with increasing concentrations of the β-adrenergic agonist isoproterenol (ISO. Interestingly, the increased frequency of arrhythmias observed in vivo in the TREU 927 infection model was lost upon isolation of the heart ex vivo, but re-emerged with the addition of ISO. Our results demonstrate that TREU 927 infection modifies the substrate of the myocardium

  16. Immunization with recombinant actin from Trypanosoma evansi induces protective immunity against T. evansi, T. equiperdum and T. b. brucei infection.

    Science.gov (United States)

    Li, San-Qiang; Yang, Wu-Biao; Lun, Zhao-Rong; Ma, Ling-Jun; Xi, Shou-Min; Chen, Qun-Li; Song, Xiao-Wei; Kang, Jian; Yang, Lan-Ze

    2009-01-01

    Actin gene of Trypanosoma evansi (STIB 806) was cloned and expressed in Escherichia coli. The predicted amino acid sequence of T. evansi actin shows 100%, 98.7%, and 93.1%, homology with Trypanosoma equiperdum, Trypanosoma brucei brucei, and Trypanosoma cruzi. Recombinant actin was expressed as inclusion bodies in E. coli. It was purified and renatured for immunological studies. Mice immunized with the renatured recombinant actin were protected from lethal challenge with T. evansi STIB 806, T. equiperdum STIB 818, and T. b. brucei STIB 940, showing 63.3%, 56.7%, and 53.3% protection, respectively. Serum collected from the rabbit immunized with recombinant actin inhibited the growth of T. evansi, T. equiperdum, and T. b. brucei in vitro cultivation. Serum from mice and rabbits immunized with recombinant actin only recognized T. evansi actin but not mouse actin. The results of this study suggest that the recombinant T. evansi actin induces protective immunity against T. evansi, T. equiperdum, and T. b. brucei infection and may be useful in the development of a vaccine with other cytoskeletal proteins to prevent animal trypanosomiasis caused by these three trypanosome species.

  17. Chemopreventive effect of methanolic extract of Azadirachta indica on experimental Trypanosoma brucei induced oxidative stress in dogs.

    Science.gov (United States)

    Omobowale, Temidayo O; Oyagbemi, Ademola A; Oyewunmi, Oyefunbi A; Adejumobi, Olumuyiwa A

    2015-01-01

    The medicinal properties of Azadirachta indica have been harnessed for many years in the treatment of many diseases in both humans and animals. Twenty-five apparently healthy dogs weighing between 3 and 8 kg were randomly divided into five groups with five dogs in each group. Ameliorative effect of A. indica on erythrocyte antioxidant status and markers of oxidative stress were assessed. Liver and kidney function tests were also performed. Pre-treatment with methanolic extract of Azadirachta indica (MEAI) at different doses did not significantly alter the values of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activity in Trypanosoma brucei infection. Although, serum creatinine significantly (P indica, after 2 weeks of T. brucei infection. However, the reduced glutathione (GSH) content of the erythrocyte increased significantly in animals pre-treated with 50 mg/kg and 200 mg/kg of A. indica respectively. Markers of oxidative stress such as malondialdehyde and hydrogen peroxide generated were higher in animals infected with T. brucei with no significant (P >0.05) difference compared to the values obtained in pre-treated animals. Pre-treatment with 100 mg/kg and 200 mg/kg of A. indica significantly (P < 0.05) decreased serum myeloperoxidase activity at 2 weeks post-infection with T. brucei. From this study, MEAI showed significant ability to attenuate oxidative stress and inflammation during experimental T. brucei infection.

  18. Sleeping sickness situation in Tanzania

    African Journals Online (AJOL)

    with primary stage infections that have not involved the central nervous system because they do not pass through the blood-brain barrier to achieve therapeutic. leveIs in the brain (2). Pentamidine, as an isethionate salt is only used against 1". gambiense. Suramin, a sulphated naphthylamine is effective against an early.

  19. The nucleotide sequence of the variable region in Trypanosoma brucei completes the sequence analysis of the maxicircle component of mitochondrial kinetoplast DNA

    NARCIS (Netherlands)

    Sloof, P.; de Haan, A.; Eier, W.; van Iersel, M.; Boel, E.; van Steeg, H.; Benne, R.

    1992-01-01

    The nucleotide sequence of two non-contiguous DNA fragments of 4.0 and 2.2 kb, respectively, of the kinetoplast maxicircle of Trypanosoma brucei brucei EATRO strain 427 has been determined, completing the sequence analysis of the so-called variable region (see also de Vries et al., 1988, Mol.

  20. PCR approach for the detection of Trypanosoma brucei and T. equiperdum and their differentiation from T. evansi based on maxicircle kinetoplast DNA.

    Science.gov (United States)

    Li, Feng-Jun; Gasser, Robin B; Lai, De-Hua; Claes, Filip; Zhu, Xing-Quan; Lun, Zhao-Rong

    2007-02-01

    The goal of this study was to develop a PCR approach based on the sequence of maxicircle kinetoplast DNA (kDNA) of Trypanosoma brucei to distinguish T. brucei/T. equiperdum from T. evansi and to evaluate its diagnostic use for their detection in blood samples. Primers derived from the sequence of the maxicircle kDNA of T. brucei, encoding the NADH dehydrogenase subunit 5 (nad5) gene, were used to test the PCR-amplification from T. brucei (including T. b. brucei and T. b. rhodesiense), T. equiperdum, T. evansi, T. vivax and T. congolense. A primer pair to a nuclear DNA region incorporated into a separate PCR was employed to control for the presence of amplifiable genomic DNA (representing the subgenus Trypanozoon) in each sample subjected to the PCR. Products of approximately 395bp were amplified from all T. brucei and T. equiperdum samples tested using the nad5-PCR, but not from T. evansi DNA samples or any of the control samples representing T. vivax, T. congolense, or host. The current PCR approach allows the rapid differentiation of T. brucei/T.equiperdum from T. evansi and can detect the equivalent of 20-25 cells of T. brucei or T. equiperdum in purified genomic DNA or infected blood samples.

  1. Identification of a bacterial-like HslVU protease in the mitochondria of Trypanosoma brucei and its role in mitochondrial DNA replication.

    Directory of Open Access Journals (Sweden)

    Ziyin Li

    2008-04-01

    Full Text Available ATP-dependent protease complexes are present in all living organisms, including the 26S proteasome in eukaryotes, Archaea, and Actinomycetales, and the HslVU protease in eubacteria. The structure of HslVU protease resembles that of the 26S proteasome, and the simultaneous presence of both proteases in one organism was deemed unlikely. However, HslVU homologs have been identified recently in some primordial eukaryotes, though their potential function remains elusive. We characterized the HslVU homolog from Trypanosoma brucei, a eukaryotic protozoan parasite and the causative agent of human sleeping sickness. TbHslVU has ATP-dependent peptidase activity and, like its bacterial counterpart, has essential lysine and N-terminal threonines in the catalytic subunit. By epitope tagging, TbHslVU localizes to mitochondria and is associated with the mitochondrial genome, kinetoplast DNA (kDNA. RNAi of TbHslVU dramatically affects the kDNA by causing over-replication of the minicircle DNA. This leads to defects in kDNA segregation and, subsequently, to continuous network growth to an enormous size. Multiple discrete foci of nicked/gapped minicircles are formed on the periphery of kDNA disc, suggesting a failure in repairing the gaps in the minicircles for kDNA segregation. TbHslVU is a eubacterial protease identified in the mitochondria of a eukaryote. It has a novel function in regulating mitochondrial DNA replication that has never been observed in other organisms.

  2. The phosphoarginine energy-buffering system of trypanosoma brucei involves multiple arginine kinase isoforms with different subcellular locations.

    Directory of Open Access Journals (Sweden)

    Frank Voncken

    Full Text Available Phosphagen energy-buffering systems play an essential role in regulating the cellular energy homeostasis in periods of high-energy demand or energy supply fluctuations. Here we describe the phosphoarginine/arginine kinase system of the kinetoplastid parasite Trypanosoma brucei, consisting of three highly similar arginine kinase isoforms (TbAK1-3. Immunofluorescence microscopy using myc-tagged protein versions revealed that each isoform is located in a specific subcellular compartment: TbAK1 is exclusively found in the flagellum, TbAK2 in the glycosome, and TbAK3 in the cytosol of T. brucei. The flagellar location of TbAK1 is dependent on a 22 amino acid long N-terminal sequence, which is sufficient for targeting a GFP-fusion protein to the trypanosome flagellum. The glycosomal location of TbAK2 is in agreement with the presence of a conserved peroxisomal targeting signal, the C-terminal tripeptide 'SNL'. TbAK3 lacks any apparent targeting sequences and is accordingly located in the cytosol of the parasite. Northern blot analysis indicated that each TbAK isoform is differentially expressed in bloodstream and procyclic forms of T. brucei, while the total cellular arginine kinase activity was 3-fold higher in bloodstream form trypanosomes. These results suggest a substantial change in the temporal and spatial energy requirements during parasite differentiation. Increased arginine kinase activity improved growth of procyclic form T. brucei during oxidative challenges with hydrogen peroxide. Elimination of the total cellular arginine kinase activity by RNA interference significantly decreased growth (>90% of procyclic form T. brucei under standard culture conditions and was lethal for this life cycle stage in the presence of hydrogen peroxide. The putative physiological roles of the different TbAK isoforms in T. brucei are further discussed.

  3. The Phosphoarginine Energy-Buffering System of Trypanosoma brucei Involves Multiple Arginine Kinase Isoforms with Different Subcellular Locations

    Science.gov (United States)

    Wadforth, Cath; Harley, Maggie; Colasante, Claudia

    2013-01-01

    Phosphagen energy-buffering systems play an essential role in regulating the cellular energy homeostasis in periods of high-energy demand or energy supply fluctuations. Here we describe the phosphoarginine/arginine kinase system of the kinetoplastid parasite Trypanosoma brucei, consisting of three highly similar arginine kinase isoforms (TbAK1-3). Immunofluorescence microscopy using myc-tagged protein versions revealed that each isoform is located in a specific subcellular compartment: TbAK1 is exclusively found in the flagellum, TbAK2 in the glycosome, and TbAK3 in the cytosol of T. brucei. The flagellar location of TbAK1 is dependent on a 22 amino acid long N-terminal sequence, which is sufficient for targeting a GFP-fusion protein to the trypanosome flagellum. The glycosomal location of TbAK2 is in agreement with the presence of a conserved peroxisomal targeting signal, the C-terminal tripeptide ‘SNL’. TbAK3 lacks any apparent targeting sequences and is accordingly located in the cytosol of the parasite. Northern blot analysis indicated that each TbAK isoform is differentially expressed in bloodstream and procyclic forms of T. brucei, while the total cellular arginine kinase activity was 3-fold higher in bloodstream form trypanosomes. These results suggest a substantial change in the temporal and spatial energy requirements during parasite differentiation. Increased arginine kinase activity improved growth of procyclic form T. brucei during oxidative challenges with hydrogen peroxide. Elimination of the total cellular arginine kinase activity by RNA interference significantly decreased growth (>90%) of procyclic form T. brucei under standard culture conditions and was lethal for this life cycle stage in the presence of hydrogen peroxide. The putative physiological roles of the different TbAK isoforms in T. brucei are further discussed. PMID:23776565

  4. Genome and phylogenetic analyses of Trypanosoma evansi reveal extensive similarity to T. brucei and multiple independent origins for dyskinetoplasty.

    Directory of Open Access Journals (Sweden)

    Jason Carnes

    2015-01-01

    Full Text Available Two key biological features distinguish Trypanosoma evansi from the T. brucei group: independence from the tsetse fly as obligatory vector, and independence from the need for functional mitochondrial DNA (kinetoplast or kDNA. In an effort to better understand the molecular causes and consequences of these differences, we sequenced the genome of an akinetoplastic T. evansi strain from China and compared it to the T. b. brucei reference strain. The annotated T. evansi genome shows extensive similarity to the reference, with 94.9% of the predicted T. b. brucei coding sequences (CDS having an ortholog in T. evansi, and 94.6% of the non-repetitive orthologs having a nucleotide identity of 95% or greater. Interestingly, several procyclin-associated genes (PAGs were disrupted or not found in this T. evansi strain, suggesting a selective loss of function in the absence of the insect life-cycle stage. Surprisingly, orthologous sequences were found in T. evansi for all 978 nuclear CDS predicted to represent the mitochondrial proteome in T. brucei, although a small number of these may have lost functionality. Consistent with previous results, the F1FO-ATP synthase γ subunit was found to have an A281 deletion, which is involved in generation of a mitochondrial membrane potential in the absence of kDNA. Candidates for CDS that are absent from the reference genome were identified in supplementary de novo assemblies of T. evansi reads. Phylogenetic analyses show that the sequenced strain belongs to a dominant group of clonal T. evansi strains with worldwide distribution that also includes isolates classified as T. equiperdum. At least three other types of T. evansi or T. equiperdum have emerged independently. Overall, the elucidation of the T. evansi genome sequence reveals extensive similarity of T. brucei and supports the contention that T. evansi should be classified as a subspecies of T. brucei.

  5. Genome and phylogenetic analyses of Trypanosoma evansi reveal extensive similarity to T. brucei and multiple independent origins for dyskinetoplasty.

    Science.gov (United States)

    Carnes, Jason; Anupama, Atashi; Balmer, Oliver; Jackson, Andrew; Lewis, Michael; Brown, Rob; Cestari, Igor; Desquesnes, Marc; Gendrin, Claire; Hertz-Fowler, Christiane; Imamura, Hideo; Ivens, Alasdair; Kořený, Luděk; Lai, De-Hua; MacLeod, Annette; McDermott, Suzanne M; Merritt, Chris; Monnerat, Severine; Moon, Wonjong; Myler, Peter; Phan, Isabelle; Ramasamy, Gowthaman; Sivam, Dhileep; Lun, Zhao-Rong; Lukeš, Julius; Stuart, Ken; Schnaufer, Achim

    2015-01-01

    Two key biological features distinguish Trypanosoma evansi from the T. brucei group: independence from the tsetse fly as obligatory vector, and independence from the need for functional mitochondrial DNA (kinetoplast or kDNA). In an effort to better understand the molecular causes and consequences of these differences, we sequenced the genome of an akinetoplastic T. evansi strain from China and compared it to the T. b. brucei reference strain. The annotated T. evansi genome shows extensive similarity to the reference, with 94.9% of the predicted T. b. brucei coding sequences (CDS) having an ortholog in T. evansi, and 94.6% of the non-repetitive orthologs having a nucleotide identity of 95% or greater. Interestingly, several procyclin-associated genes (PAGs) were disrupted or not found in this T. evansi strain, suggesting a selective loss of function in the absence of the insect life-cycle stage. Surprisingly, orthologous sequences were found in T. evansi for all 978 nuclear CDS predicted to represent the mitochondrial proteome in T. brucei, although a small number of these may have lost functionality. Consistent with previous results, the F1FO-ATP synthase γ subunit was found to have an A281 deletion, which is involved in generation of a mitochondrial membrane potential in the absence of kDNA. Candidates for CDS that are absent from the reference genome were identified in supplementary de novo assemblies of T. evansi reads. Phylogenetic analyses show that the sequenced strain belongs to a dominant group of clonal T. evansi strains with worldwide distribution that also includes isolates classified as T. equiperdum. At least three other types of T. evansi or T. equiperdum have emerged independently. Overall, the elucidation of the T. evansi genome sequence reveals extensive similarity of T. brucei and supports the contention that T. evansi should be classified as a subspecies of T. brucei.

  6. Mammalian sleep

    Science.gov (United States)

    Staunton, Hugh

    2005-05-01

    This review examines the biological background to the development of ideas on rapid eye movement sleep (REM sleep), so-called paradoxical sleep (PS), and its relation to dreaming. Aspects of the phenomenon which are discussed include physiological changes and their anatomical location, the effects of total and selective sleep deprivation in the human and animal, and REM sleep behavior disorder, the latter with its clinical manifestations in the human. Although dreaming also occurs in other sleep phases (non-REM or NREM sleep), in the human, there is a contingent relation between REM sleep and dreaming. Thus, REM is taken as a marker for dreaming and as REM is distributed ubiquitously throughout the mammalian class, it is suggested that other mammals also dream. It is suggested that the overall function of REM sleep/dreaming is more important than the content of the individual dream; its function is to place the dreamer protagonist/observer on the topographical world. This has importance for the developing infant who needs to develop a sense of self and separateness from the world which it requires to navigate and from which it is separated for long periods in sleep. Dreaming may also serve to maintain a sense of ‘I’ness or “self” in the adult, in whom a fragility of this faculty is revealed in neurological disorders.

  7. Genome-wide analysis of chromatin structures in Trypanosoma brucei using high-resolution MNase-ChIP-seq.

    Science.gov (United States)

    Wedel, Carolin; Siegel, T Nicolai

    2017-09-01

    Specific DNA-protein interactions are the basis for many important cellular mechanisms like the regulation of gene expression or replication. Knowledge about the precise genomic locations of DNA-protein interactions is important because it provides insight into the regulation of these processes. Recently, we have adapted an approach that combines micrococcal nuclease (MNase) digestion of chromatin with chromatin immunoprecipitation in Trypanosoma brucei. Here, we describe in detail how this method can be used to map the genome-wide distribution of nucleosomes or other DNA-binding proteins at high resolution in T. brucei. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Pyrimidine Salvage Enzymes Are Essential for De Novo Biosynthesis of Deoxypyrimidine Nucleotides in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Christopher Leija

    2016-11-01

    Full Text Available The human pathogenic parasite Trypanosoma brucei possess both de novo and salvage routes for the biosynthesis of pyrimidine nucleotides. Consequently, they do not require salvageable pyrimidines for growth. Thymidine kinase (TK catalyzes the formation of dTMP and dUMP and is one of several salvage enzymes that appear redundant to the de novo pathway. Surprisingly, we show through analysis of TK conditional null and RNAi cells that TK is essential for growth and for infectivity in a mouse model, and that a catalytically active enzyme is required for its function. Unlike humans, T. brucei and all other kinetoplastids lack dCMP deaminase (DCTD, which provides an alternative route to dUMP formation. Ectopic expression of human DCTD resulted in full rescue of the RNAi growth phenotype and allowed for selection of viable TK null cells. Metabolite profiling by LC-MS/MS revealed a buildup of deoxypyrimidine nucleosides in TK depleted cells. Knockout of cytidine deaminase (CDA, which converts deoxycytidine to deoxyuridine led to thymidine/deoxyuridine auxotrophy. These unexpected results suggested that T. brucei encodes an unidentified 5'-nucleotidase that converts deoxypyrimidine nucleotides to their corresponding nucleosides, leading to their dead-end buildup in TK depleted cells at the expense of dTTP pools. Bioinformatics analysis identified several potential candidate genes that could encode 5'-nucleotidase activity including an HD-domain protein that we show catalyzes dephosphorylation of deoxyribonucleotide 5'-monophosphates. We conclude that TK is essential for synthesis of thymine nucleotides regardless of whether the nucleoside precursors originate from the de novo pathway or through salvage. Reliance on TK in the absence of DCTD may be a shared vulnerability among trypanosomatids and may provide a unique opportunity to selectively target a diverse group of pathogenic single-celled eukaryotes with a single drug.

  9. Knockdown of asparagine synthetase A renders Trypanosoma brucei auxotrophic to asparagine.

    Directory of Open Access Journals (Sweden)

    Inês Loureiro

    Full Text Available Asparagine synthetase (AS catalyzes the ATP-dependent conversion of aspartate into asparagine using ammonia or glutamine as nitrogen source. There are two distinct types of AS, asparagine synthetase A (AS-A, known as strictly ammonia-dependent, and asparagine synthetase B (AS-B, which can use either ammonia or glutamine. The absence of AS-A in humans, and its presence in trypanosomes, suggested AS-A as a potential drug target that deserved further investigation. We report the presence of functional AS-A in Trypanosoma cruzi (TcAS-A and Trypanosoma brucei (TbAS-A: the purified enzymes convert L-aspartate into L-asparagine in the presence of ATP, ammonia and Mg(2+. TcAS-A and TbAS-A use preferentially ammonia as a nitrogen donor, but surprisingly, can also use glutamine, a characteristic so far never described for any AS-A. TbAS-A knockdown by RNAi didn't affect in vitro growth of bloodstream forms of the parasite. However, growth was significantly impaired when TbAS-A knockdown parasites were cultured in medium with reduced levels of asparagine. As expected, mice infections with induced and non-induced T. brucei RNAi clones were similar to those from wild-type parasites. However, when induced T. brucei RNAi clones were injected in mice undergoing asparaginase treatment, which depletes blood asparagine, the mice exhibited lower parasitemia and a prolonged survival in comparison to similarly-treated mice infected with control parasites. Our results show that TbAS-A can be important under in vivo conditions when asparagine is limiting, but is unlikely to be suitable as a drug target.

  10. Chemical characterisation of Nigerian red propolis and its biological activity against Trypanosoma Brucei.

    Science.gov (United States)

    Omar, Ruwida M K; Igoli, John; Gray, Alexander I; Ebiloma, Godwin Unekwuojo; Clements, Carol; Fearnley, James; Ebel, Ru Angeli Edrada; Zhang, Tong; De Koning, Harry P; Watson, David G

    2016-01-01

    A previous study showed the unique character of Nigerian red propolis from Rivers State, Nigeria (RSN), with regards to chemical composition and activity against Trypanosoma brucei in comparison with other African propolis. To carry out fractionation and biological testing of Nigerian propolis in order to isolate compounds with anti-trypanosomal activity. To compare the composition of the RSN propolis with the composition of Brazilian red propolis. Profiling was carried out using HPLC-UV-ELSD and HPLC-Orbitrap-FTMS on extracts of two samples collected from RSN with data extraction using MZmine software. Isolation was carried out by normal phase and reversed phase MPLC. Elucidation of the compounds with a purity > 95% was performed by 1D/2D NMR HRMS and HRLC-MS(n) . Ten phenolic compounds were isolated or in the case of liquiritigenin partially purified. Data for nine of these correlated with literature reports of known compounds i.e. one isoflavanone, calycosin (1); two flavanones, liquiritigenin (2) and pinocembrin (5); an isoflavan, vestitol (3); a pterocarpan, medicarpin (4); two prenylflavanones, 8-prenylnaringenin (7) and 6-prenylnaringenin (8); and two geranyl flavonoids, propolin D (9) and macarangin (10). The tenth was elucidated as a previously undescribed dihydrobenzofuran (6). The isolated compounds were tested against Trypanosoma brucei and displayed moderate to high activity. Some of the compounds tested had similar activity against wild type T. brucei and two strains displaying pentamidine resistance. Nigerian propolis from RSN has some similarities with Brazilian red propolis. The propolis displayed anti-trypanosomal activity at a potentially useful level. Copyright © 2015 John Wiley & Sons, Ltd.

  11. The transcriptome of the human pathogen Trypanosoma brucei at single-nucleotide resolution.

    Directory of Open Access Journals (Sweden)

    Nikolay G Kolev

    2010-09-01

    Full Text Available The genome of Trypanosoma brucei, the causative agent of African trypanosomiasis, was published five years ago, yet identification of all genes and their transcripts remains to be accomplished. Annotation is challenged by the organization of genes transcribed by RNA polymerase II (Pol II into long unidirectional gene clusters with no knowledge of how transcription is initiated. Here we report a single-nucleotide resolution genomic map of the T. brucei transcriptome, adding 1,114 new transcripts, including 103 non-coding RNAs, confirming and correcting many of the annotated features and revealing an extensive heterogeneity of 5' and 3' ends. Some of the new transcripts encode polypeptides that are either conserved in T. cruzi and Leishmania major or were previously detected in mass spectrometry analyses. High-throughput RNA sequencing (RNA-Seq was sensitive enough to detect transcripts at putative Pol II transcription initiation sites. Our results, as well as recent data from the literature, indicate that transcription initiation is not solely restricted to regions at the beginning of gene clusters, but may occur at internal sites. We also provide evidence that transcription at all putative initiation sites in T. brucei is bidirectional, a recently recognized fundamental property of eukaryotic promoters. Our results have implications for gene expression patterns in other important human pathogens with similar genome organization (Trypanosoma cruzi, Leishmania sp. and revealed heterogeneity in pre-mRNA processing that could potentially contribute to the survival and success of the parasite population in the insect vector and the mammalian host.

  12. Central sleep apnea

    Science.gov (United States)

    Sleep apnea - central; Obesity - central sleep apnea; Cheyne-Stokes - central sleep apnea; Heart failure - central sleep apnea ... Central sleep apnea results when the brain temporarily stops sending signals to the muscles that control breathing. The condition ...

  13. Sleep disorders - overview

    Science.gov (United States)

    Insomnia; Narcolepsy; Hypersomina; Daytime sleepiness; Sleep rhythm; Sleep disruptive behaviors; Jet lag ... excessive daytime sleepiness) Problems sticking to a regular sleep schedule (sleep rhythm problem) Unusual behaviors during sleep ( ...

  14. Trypanosoma brucei Co-opts NK Cells to Kill Splenic B2 B Cells.

    Directory of Open Access Journals (Sweden)

    Deborah Frenkel

    2016-07-01

    Full Text Available After infection with T. brucei AnTat 1.1, C57BL/6 mice lost splenic B2 B cells and lymphoid follicles, developed poor parasite-specific antibody responses, lost weight, became anemic and died with fulminating parasitemia within 35 days. In contrast, infected C57BL/6 mice lacking the cytotoxic granule pore-forming protein perforin (Prf1-/- retained splenic B2 B cells and lymphoid follicles, developed high-titer antibody responses against many trypanosome polypeptides, rapidly suppressed parasitemia and did not develop anemia or lose weight for at least 60 days. Several lines of evidence show that T. brucei infection-induced splenic B cell depletion results from natural killer (NK cell-mediated cytotoxicity: i B2 B cells were depleted from the spleens of infected intact, T cell deficient (TCR-/- and FcγRIIIa deficient (CD16-/- C57BL/6 mice excluding a requirement for T cells, NKT cell, or antibody-dependent cell-mediated cytotoxicity; ii administration of NK1.1 specific IgG2a (mAb PK136 but not irrelevant IgG2a (myeloma M9144 prevented infection-induced B cell depletion consistent with a requirement for NK cells; iii splenic NK cells but not T cells or NKT cells degranulated in infected C57BL/6 mice co-incident with B cell depletion evidenced by increased surface expression of CD107a; iv purified NK cells from naïve C57BL/6 mice killed purified splenic B cells from T. brucei infected but not uninfected mice in vitro indicating acquisition of an NK cell activating phenotype by the post-infection B cells; v adoptively transferred C57BL/6 NK cells prevented infection-induced B cell population growth in infected Prf1-/- mice consistent with in vivo B cell killing; vi degranulated NK cells in infected mice had altered gene and differentiation antigen expression and lost cytotoxic activity consistent with functional exhaustion, but increased in number as infection progressed indicating continued generation. We conclude that NK cells in T. brucei

  15. Variation of G-rich mitochondrial transcripts among stocks of Trypanosoma brucei.

    Science.gov (United States)

    Jasmer, D P; Feagin, J E; Payne, M; Stuart, K

    1987-01-15

    We have compared maxicircle transcripts from eight stocks of subspecies of Trypanosoma brucei. Transcripts from the rRNA and protein genes have a constant size among stocks and exhibit only minor variation in abundance. In contrast, four of the G+C rich sequences encode multiple transcripts that very markedly in size or abundance. Maxicircle nucleotide sequence comparison of three stocks shows very limited sequence divergence suggesting that sequence divergence may not explain the transcript variability. These results suggest that the G-rich transcripts do not encode proteins and that their variability among stocks may result from posttranscriptional processing events.

  16. A literature review of economic evaluations for a neglected tropical disease: human African trypanosomiasis ("sleeping sickness").

    Science.gov (United States)

    Sutherland, C Simone; Yukich, Joshua; Goeree, Ron; Tediosi, Fabrizio

    2015-02-01

    Human African trypanosomiasis (HAT) is a disease caused by infection with the parasite Trypanosoma brucei gambiense or T. b. rhodesiense. It is transmitted to humans via the tsetse fly. Approximately 70 million people worldwide were at risk of infection in 1995, and approximately 20,000 people across Africa are infected with HAT. The objective of this review was to identify existing economic evaluations in order to summarise cost-effective interventions to reduce, control, or eliminate the burden of HAT. The studies included in the review were compared and critically appraised in order to determine if there were existing standardised methods that could be used for economic evaluation of HAT interventions or if innovative methodological approaches are warranted. A search strategy was developed using keywords and was implemented in January 2014 in several databases. The search returned a total of 2,283 articles. After two levels of screening, a total of seven economic evaluations were included and underwent critical appraisal using the Scottish Intercollegiate Guidelines Network (SIGN) Methodology Checklist 6: Economic Evaluations. Results from the existing studies focused on the cost-effectiveness of interventions for the control and reduction of disease transmission. Modelling was a common method to forecast long-term results, and publications focused on interventions by category, such as case detection, diagnostics, drug treatments, and vector control. Most interventions were considered cost-effective based on the thresholds described; however, the current treatment, nifurtomix-eflornithine combination therapy (NECT), has not been evaluated for cost-effectiveness, and considerations for cost-effective strategies for elimination have yet to be completed. Overall, the current evidence highlights the main components that play a role in control; however, economic evaluations of HAT elimination strategies are needed to assist national decision makers, stakeholders, and

  17. Gene fusion analysis in the battle against the African endemic sleeping sickness.

    Directory of Open Access Journals (Sweden)

    Philip Trimpalis

    Full Text Available The protozoan Trypanosoma brucei causes African Trypanosomiasis or sleeping sickness in humans, which can be lethal if untreated. Most available pharmacological treatments for the disease have severe side-effects. The purpose of this analysis was to detect novel protein-protein interactions (PPIs, vital for the parasite, which could lead to the development of drugs against this disease to block the specific interactions. In this work, the Domain Fusion Analysis (Rosetta Stone method was used to identify novel PPIs, by comparing T. brucei to 19 organisms covering all major lineages of the tree of life. Overall, 49 possible protein-protein interactions were detected, and classified based on (a statistical significance (BLAST e-value, domain length etc., (b their involvement in crucial metabolic pathways, and (c their evolutionary history, particularly focusing on whether a protein pair is split in T. brucei and fused in the human host. We also evaluated fusion events including hypothetical proteins, and suggest a possible molecular function or involvement in a certain biological process. This work has produced valuable results which could be further studied through structural biology or other experimental approaches so as to validate the protein-protein interactions proposed here. The evolutionary analysis of the proteins involved showed that, gene fusion or gene fission events can happen in all organisms, while some protein domains are more prone to fusion and fission events and present complex evolutionary patterns.

  18. Identification of Trypanosome Proteins in Plasma from African Sleeping Sickness Patients Infected with T. b. rhodesiense

    Science.gov (United States)

    Enyaru, John C.; Carr, Steven A.; Pearson, Terry W.

    2013-01-01

    Control of human African sleeping sickness, caused by subspecies of the protozoan parasite Trypanosoma brucei, is based on preventing transmission by elimination of the tsetse vector and by active diagnostic screening and treatment of infected patients. To identify trypanosome proteins that have potential as biomarkers for detection and monitoring of African sleeping sickness, we have used a ‘deep-mining” proteomics approach to identify trypanosome proteins in human plasma. Abundant human plasma proteins were removed by immunodepletion. Depleted plasma samples were then digested to peptides with trypsin, fractionated by basic reversed phase and each fraction analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This sample processing and analysis method enabled identification of low levels of trypanosome proteins in pooled plasma from late stage sleeping sickness patients infected with Trypanosoma brucei rhodesiense. A total of 254 trypanosome proteins were confidently identified. Many of the parasite proteins identified were of unknown function, although metabolic enzymes, chaperones, proteases and ubiquitin-related/acting proteins were found. This approach to the identification of conserved, soluble trypanosome proteins in human plasma offers a possible route to improved disease diagnosis and monitoring, since these molecules are potential biomarkers for the development of a new generation of antigen-detection assays. The combined immuno-depletion/mass spectrometric approach can be applied to a variety of infectious diseases for unbiased biomarker identification. PMID:23951171

  19. Structural and functional insight into ADF/cofilin from Trypanosoma brucei.

    Science.gov (United States)

    Dai, Kun; Liao, Shanhui; Zhang, Jiahai; Zhang, Xuecheng; Tu, Xiaoming

    2013-01-01

    The ADF/cofilin family has been characterized as a group of actin-binding proteins critical for controlling the assembly of actin within the cells. In this study, the solution structure of the ADF/cofilin from Trypanosoma brucei (TbCof) was determined by NMR spectroscopy. TbCof adopts the conserved ADF/cofilin fold with a central β-sheet composed of six β-strands surrounded by five α-helices. Isothermal titration calorimetry experiments denoted a submicromolar affinity between TbCof and G-actin, and the affinity between TbCof and ADP-G-actin was five times higher than that between TbCof and ATP-G-actin at low ionic strength. The results obtained from electron microscopy and actin filament sedimentation assays showed that TbCof depolymerized but did not co-sediment with actin filaments and its ability of F-actin depolymerization was pH independent. Similar to actin, TbCof was distributed throughout the cytoplasm. All our data indicate a structurally and functionally conserved ADF/cofilin from Trypanosoma brucei.

  20. Structural and Functional Association of Trypanosoma brucei MIX Protein with Cytochrome c Oxidase Complex ▿ †

    Science.gov (United States)

    Zíková, Alena; Panigrahi, Aswini K.; Uboldi, Alessandro D.; Dalley, Rachel A.; Handman, Emanuela; Stuart, Kenneth

    2008-01-01

    A mitochondrial inner membrane protein, designated MIX, seems to be essential for cell viability. The deletion of both alleles was not possible, and the deletion of a single allele led to a loss of virulence and aberrant mitochondrial segregation and cell division in Leishmania major. However, the mechanism by which MIX exerts its effect has not been determined. We show here that MIX is also expressed in the mitochondrion of Trypanosoma brucei, and using RNA interference, we found that its loss leads to a phenotype that is similar to that described for Leishmania. The loss of MIX also had a major effect on cytochrome c oxidase activity, on the mitochondrial membrane potential, and on the production of mitochondrial ATP by oxidative phosphorylation. Using a tandem affinity purification tag, we found that MIX is associated with a multiprotein complex that contains subunits of the mitochondrial cytochrome c oxidase complex (respiratory complex IV), the composition of which was characterized in detail. The specific function of MIX is unknown, but it appears to be important for the function of complex IV and for mitochondrial segregation and cell division in T. brucei. PMID:18776036

  1. Base J and H3.V Regulate Transcriptional Termination in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Danae Schulz

    2016-01-01

    Full Text Available Trypanosoma brucei is a protozoan parasite that lacks many transcription factors found in other eukaryotes, such as those whose binding demarcates enhancers. T. brucei retains histone variants and modifications, however, and it is hypothesized that it relies on epigenetic marks to define transcription-related boundaries. The histone H3 variant (H3.V and an alternate nucleotide, base J (ß-D-glucosyl-hydroxymethyluracil, are two chromatin marks found at both transcription termination sites (TTSs and telomeres. Here, we report that the absence of both base J and H3.V result in transcription readthrough and the appearance of antisense transcripts near TTSs. Additionally, we find that maintaining the transcriptional silencing of pol I-transcribed telomeric Variant Surface Glycoprotein (VSG genes appears to be dependent on deposition of H3.V alone. Our study reveals that gene expression depends on different epigenetic cues depending on chromosomal location and on the transcribing polymerase. This work provides insight into how these signals may have evolved into the more nuanced and fine-tuned gene regulatory mechanisms observed in other model systems.

  2. Tail characteristics of Trypanosoma brucei mitochondrial transcripts are developmentally altered in a transcript-specific manner.

    Science.gov (United States)

    Gazestani, Vahid H; Hampton, Marshall; Shaw, Aubie K; Salavati, Reza; Zimmer, Sara L

    2018-02-01

    The intricate life cycle of Trypanosoma brucei requires extensive regulation of gene expression levels of the mtRNAs for adaptation. Post-transcriptional gene regulatory programs, including unencoded mtRNA 3' tail additions, potentially play major roles in this adaptation process. Intriguingly, T. brucei mitochondrial transcripts possess two distinct unencoded 3' tails, each with a differing functional role; i.e., while one type is implicated in RNA stability (in-tails), the other type appears associated with translation (ex-tails). We examined the degree to which tail characteristics differ among cytochrome c oxidase subunits I and III (CO1 and CO3), and NADH dehydrogenase subunit 1 (ND1) transcripts, and to what extent these characteristics differ developmentally. We found that CO1, CO3 and ND1 transcripts possess longer in-tails in the mammalian life stage. By mathematically modelling states of in-tail and ex-tail addition, we determined that the typical length at which an in-tail is extended to become an ex-tail differs by transcript and, in the case of ND1, by life stage. To the best of our knowledge, we provide the first evidence that developmental differences exist in tail length distributions of mtRNAs, underscoring the potential involvement of in-tail and ex-tail populations in mitochondrial post-transcriptional regulation mechanisms. Copyright © 2017 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

  3. Investigating the Chaperone Properties of a Novel Heat Shock Protein, Hsp70.c, from Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Adélle Burger

    2014-01-01

    Full Text Available The neglected tropical disease, African Trypanosomiasis, is fatal and has a crippling impact on economic development. Heat shock protein 70 (Hsp70 is an important molecular chaperone that is expressed in response to stress and Hsp40 acts as its co-chaperone. These proteins play a wide range of roles in the cell and they are required to assist the parasite as it moves from a cold blooded insect vector to a warm blooded mammalian host. A novel cytosolic Hsp70, from Trypanosoma brucei, TbHsp70.c, contains an acidic substrate binding domain and lacks the C-terminal EEVD motif. The ability of a cytosolic Hsp40 from Trypanosoma brucei J protein 2, Tbj2, to function as a co-chaperone of TbHsp70.c was investigated. The main objective was to functionally characterize TbHsp70.c to further expand our knowledge of parasite biology. TbHsp70.c and Tbj2 were heterologously expressed and purified and both proteins displayed the ability to suppress aggregation of thermolabile MDH and chemically denatured rhodanese. ATPase assays revealed a 2.8-fold stimulation of the ATPase activity of TbHsp70.c by Tbj2. TbHsp70.c and Tbj2 both demonstrated chaperone activity and Tbj2 functions as a co-chaperone of TbHsp70.c. In vivo heat stress experiments indicated upregulation of the expression levels of TbHsp70.c.

  4. KREX2 is not essential for either procyclic or bloodstream form Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Jason Carnes

    Full Text Available BACKGROUND: Most mitochondrial mRNAs in Trypanosoma brucei require RNA editing for maturation and translation. The edited RNAs primarily encode proteins of the oxidative phosphorylation system. These parasites undergo extensive changes in energy metabolism between the insect and bloodstream stages which are mirrored by alterations in RNA editing. Two U-specific exonucleases, KREX1 and KREX2, are both present in protein complexes (editosomes that catalyze RNA editing but the relative roles of each protein are not known. METHODOLOGY/PRINCIPAL FINDINGS: The requirement for KREX2 for RNA editing in vivo was assessed in both procyclic (insect and bloodstream form parasites by methods that use homologous recombination for gene elimination. These studies resulted in null mutant cells in which both alleles were eliminated. The viability of these cells demonstrates that KREX2 is not essential in either life cycle stage, despite certain defects in RNA editing in vivo. Furthermore, editosomes isolated from KREX2 null cells require KREX1 for in vitro U-specific exonuclease activity. CONCLUSIONS: KREX2 is a U-specific exonuclease that is dispensable for RNA editing in vivo in T. brucei BFs and PFs. This result suggests that the U deletion activity, which is required for RNA editing, is primarily mediated in vivo by KREX1 which is normally found associated with only one type of editosome. The retention of the KREX2 gene implies a non-essential role or a role that is essential in other life cycle stages or conditions.

  5. Secondary metabolites from Vietnamese marine invertebrates with activity against Trypanosoma brucei and T. cruzi.

    Science.gov (United States)

    Thao, Nguyen Phuong; No, Joo Hwan; Luyen, Bui Thi Thuy; Yang, Gyongseon; Byun, Soo Young; Goo, Junghyun; Kim, Kyung Tae; Cuong, Nguyen Xuan; Nam, Nguyen Hoai; Van Minh, Chau; Schmidt, Thomas J; Kang, Jong Seong; Kim, Young Ho

    2014-06-11

    Marine-derived natural products from invertebrates comprise an extremely diverse and promising source of the compounds from a wide variety of structural classes. This study describes the discovery of five marine natural products with activity against Trypanosoma species by natural product library screening using whole cell in vitro assays. We investigated the anti-trypanosomal activity of the extracts from the soft corals and echinoderms living in Vietnamese seas. Of the samples screened, the methanolic extracts of several marine organisms exhibited potent activities against cultures of Trypanosoma brucei and T. cruzi (EC50 activity against T. brucei with EC50 values ranging from 1.57 ± 0.14 to 14.6 ± 1.36 μM, relative to the positive control, pentamidine (EC50 = 0.015 ± 0.003 μM). Laevigatol B (1) and 5α-cholest-8(14)-ene-3β,7α-diol (5) exhibited also significant inhibitory effects on T. cruzi. The cytotoxic activity of the pure compounds on mammalian cells was also assessed and found to be insignificant in all cases. This is the first report on the inhibitory effects of marine organisms collected in Vietnamese seas against Trypanosoma species responsible for neglected tropical diseases.

  6. Sleep walking

    Science.gov (United States)

    ... during REM sleep, it is part of REM behavior disorder and tends to happen near morning. As people age, they have less N3 sleep. This is why sleepwalking is much more common in children and young adults. The cause of sleepwalking in children is usually ...

  7. 1H, 13C and 15N resonance assignments for a putative ADF/Cofilin from Trypanosoma brucei.

    Science.gov (United States)

    Dai, Kun; Yuan, Guangfa; Liao, Shanhui; Zhang, Jiahai; Tu, Xiaoming

    2011-10-01

    Actin-depolymerizing factor (ADF)/cofilin proteins are a family of actin-binding proteins expressed in almost all eukaryotic cells, and play a significant role in regulating actin-filament dynamics. Here we report the resonance assignments of a putative ADF/cofilin from Trypanosoma brucei for further understanding of the relationship between its structure and function.

  8. Variations in maxi-circle and mini-circle sequences in kinetoplast DNAs from different Trypanosoma brucei strains.

    NARCIS (Netherlands)

    P. Borst (Piet); F. Fase-Fowler; J.H.J. Hoeijmakers (Jan); A.C.C. Frasch

    1980-01-01

    textabstractWe have compared a total of 30 recognition sites for eight restriction endonucleases on the 20-kilobase-pair maxi-circle of kinetoplast DNAs from five different Trypanosoma brucei strains. In addition to three polymorphic sites were have found a 5 kilobase-pair region that is not cleaved

  9. THE CYTOSOLIC AND GLYCOSOMAL GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE FROM TRYPANOSOMA-BRUCEI - KINETIC-PROPERTIES AND COMPARISON WITH HOMOLOGOUS ENZYMES

    NARCIS (Netherlands)

    LAMBEIR, AM; LOISEAU, AM; KUNTZ, DA; VELLIEUX, FM; MICHELS, PAM; OPPERDOES, FR

    1991-01-01

    The protozoan haemoflagellate Trypanosoma brucei has two NAD-dependent glyceraldehyde-3-phosphate dehydrogenase isoenzymes, each with a different localization within the cell. One isoenzyme is found in the cytosol, as in other eukaryotes, while the other is found in the glycosome, a microbody-like

  10. Haematological indices in Trypanosoma brucei brucei (Federe isolate infected Nigerian donkeys (Equus asinus treated with homidium and isometamidium chloride of ciprofloxacin in broiler chickens after single intravenous and intraingluvial administration

    Directory of Open Access Journals (Sweden)

    Queen Nneka Oparah

    2017-03-01

    Full Text Available The efficacy of intramuscular administration of Homidium chloride (Novidium® and Isometamidium chloride (Sécuridium® in Nigerian donkeys (Equus asinus experimentally infected with T. b. brucei (Federe isolate was investigated. Changes in haematological and serum biochemical indices were evaluated using clinical haematology and biochemistry methods. Red blood cell (RBC count for the negative control group was significantly higher than for the positive control, Novidium® and Sécuridium®-treatment groups. Haemoglobin (Hb concentration significantly reduced in the infected untreated group compared with other groups. Packed cell volume (PCV was significantly different between negative and positive controls, and also between the infected untreated and treatment groups. There was significant reduction in platelet counts post-infection and post-treatment. Mean corpuscular volume (MCV increased significantly in the treatment groups while mean corpuscular haemoglobin concentration (MCHC significantly reduced only in the Sécuridium®-treatment group. Lymphocyte count for infected untreated was non-significantly higher than for the uninfected controls, but treatment with both trypanocides recorded further increases, which were higher compared with that of the uninfected group. Post infection and treatment, aspartate aminotransferase (AST levels increased significantly. There were non-significant differences in electrolyte ion concentrations across the groups except for chloride ion which recorded a significant reduction in the Novidium®-treatment group. This experiment revealed that Nigerian donkeys infected with T. brucei brucei (Federe isolate developed symptoms of trypanosomosis; anaemia, lymphocytosis and thrombocytopenia. Treatment with the trypanocides ameliorated effects of the infection, and results suggest that immunosuppression may not be a substantial clinical manifestation of T. brucei brucei (Federe isolate trypanosomosis in Nigerian

  11. Sulfhydryl reagent susceptibility in proteins with high sequence similarity--triosephosphate isomerase from Trypanosoma brucei, Trypanosoma cruzi and Leishmania mexicana.

    Science.gov (United States)

    Garza-Ramos, G; Cabrera, N; Saavedra-Lira, E; Tuena de Gómez-Puyou, M; Ostoa-Saloma, P; Pérez-Montfort, R; Gómez-Puyou, A

    1998-05-01

    The amino acid sequence of triosephosphate isomerase from Trypanosoma brucei, Trypanosoma cruzi, and Leishmania mexicana have an identity of 68%. Using the numbering system for the T. brucei enzyme, in their aligned sequences, the T. cruzi and leishmanial enzymes have cysteine residues at positions 14, 40, 117 and 126. T. brucei triosephosphate isomerase has cysteine residues at positions 14, 40 and 126, and a valine residue at position 117. Dithionitrobenzoic acid and methylmethane thiosulfonate inhibited the three enzymes, but T. cruzi triosephosphate isomerase was more than 100-fold more sensitive. The sensitivity of wild type triosephosphate isomerase from T. cruzi and T. brucei to the reagents was equal to that of the Cys117Val and Val117Cys mutant enzymes, respectively. Triosephosphate isomerases that have cysteine residues at positions 40 and 126, but lack a cysteine residue at position 14 are insensitive to methylmethane thiosulfonate. Thus, sulfhydryl reagents act on Cys14. At stoichiometric concentrations, the reagents inhibited the three enzymes as a consequence of structural alterations as measured by binding of 8-anilino-1-napthalenesulfonic acid to previously buried hydrophobic regions. However, the times for half-maximal alterations were 10 min, 15 hours and over 30 hours for T. cruzi, T. brucei and L. mexicana triosephosphate isomerase, respectively. The effect of pH on the action of the sulfhydryl reagents and molecular modeling showed no differences in the solvent accessibility of Cys14. As Cys14 forms part of the dimer interface, the data indicate that, in the three enzymes, barriers of different magnitude hinder the interaction between the sulfhydryl reagents and Cys14. The barrier is lower in T. cruzi triosephosphate isomerase which makes its dimer interface more susceptible for perturbation.

  12. Molecular profiles of Trypanosoma brucei, T. evansi and T. equiperdum stocks revealed by the random amplified polymorphic DNA method.

    Science.gov (United States)

    Lun, Zhao-Rong; Li, An-Xing; Chen, Xiao-Guang; Lu, Li-Xin; Zhu, Xing-Quan

    2004-03-01

    A total of 20 random primers (10-mers) were used to amplify RAPD markers from the genomic DNA of four Trypanosoma brucei stocks from East and West Africa, four T. evansi stocks from Africa, Asia and South America and one T. equiperdum stock from Asia. Between 65 and 88 reproducible fragments ranging from 0.25 to 2.15 kb were generated from these stocks depending on the stock/primer combination. The similarity coefficient (SC) among the stocks of T. brucei from Kenya, Nigeria, Tanzania and Zambia ranged from 62.9% to 74.0% (average: 67.6%). The SC among the stocks of T. evansi from Kenya, China and Brazil was 76.4%-95.5% (average: 86.4%), while the SC between T. evansi stock from China and Brazil was 95.5%. For T. evansi and T. equiperdum, the SC among the stocks ranged from 81.2% to 94.4% (average: 87.6%). As for the SC among the stocks of T. brucei and T. evansi, it was found to be from 54.7% to 80.3% (average: 68.0%) and the SC among stocks of T. brucei and T. equiperdum was from 59.4% to 76.9% (average: 68.1%). Our results indicate that the stocks of T. evansi from China and from Brazil are more closely related to the stock of T. equiperdum from China than to the stocks of T. evansi isolated from Kenya and to the stocks of T. brucei. In addition, our results further support the hypothesis that T. evansi stocks from China and Brazil could have arisen from a single lineage. The possible evolution of T. evansi and T. equiperdum is also discussed.

  13. Medicines for sleep

    Science.gov (United States)

    Benzodiazepines; Sedatives; Hypnotics; Sleeping pills; Insomnia - medicines; Sleep disorder - medicines ... are commonly used to treat allergies. While these sleep aids are not addictive, your body becomes used ...

  14. PHYTOREMEDIATION POTENTIAL OF Vigna unguiculata IN A ...

    African Journals Online (AJOL)

    FRANK

    Infection of four baboons with Trypanosma brucei gambiense resulted in a prepatent period of 3 – 4 days. Following the first appearance of T. b. gambiense parasitaemia, the animals developed trypanosomosis characterised by elevated parasite counts in the blood, fever, increased heart and respiratory rates and increased ...

  15. An Assessment Of The Efficacy Of Dfmo In Baboons (Papio Anubis ...

    African Journals Online (AJOL)

    Infection of four baboons with Trypanosma brucei gambiense resulted in a prepatent period of 3 – 4 days. Following the first appearance of T. b. gambiense parasitaemia, the animals developed trypanosomosis characterised by elevated parasite counts in the blood, fever, increased heart and respiratory rates and increased ...

  16. Further evidence from SSCP and ITS DNA sequencing support Trypanosoma evansi and Trypanosoma equiperdum as subspecies or even strains of Trypanosoma brucei

    OpenAIRE

    Wen, Y; Lun, Z; Zhu, X; Hide, G; Lai, D

    2016-01-01

    The subgenus Trypanozoon includes three species Trypanosoma brucei, Trypanosoma evansi and Trypanosoma equiperdum, which are morphologically identical and indistinguishable even using some molecular methods. In this study, PCR-based single strand conformation polymorphism (PCR-SSCP) was used to analyze the ribosomal DNA of the Trypanozoon species. Data indicate different patterns of ITS2 fragments between T. brucei, T. evansi and T. equiperdum by SSCP. Furthermore, analysis of total ITS seque...

  17. Expression of interferon-inducible chemokines and sleep/wake changes during early encephalitis in experimental African trypanosomiasis.

    Science.gov (United States)

    Laperchia, Claudia; Tesoriero, Chiara; Seke-Etet, Paul F; La Verde, Valentina; Colavito, Valeria; Grassi-Zucconi, Gigliola; Rodgers, Jean; Montague, Paul; Kennedy, Peter G E; Bentivoglio, Marina

    2017-08-01

    Human African trypanosomiasis or sleeping sickness, caused by the parasite Trypanosoma brucei, leads to neuroinflammation and characteristic sleep/wake alterations. The relationship between the onset of these alterations and the development of neuroinflammation is of high translational relevance, but remains unclear. This study investigates the expression of interferon (IFN)-γ and IFN-inducible chemokine genes in the brain, and the levels of CXCL10 in the serum and cerebrospinal fluid prior to and during the encephalitic stage of trypanosome infection, and correlates these with sleep/wake changes in a rat model of the disease. The expression of genes encoding IFN-γ, CXCL9, CXCL10, and CXCL11 was assessed in the brain of rats infected with Trypanosoma brucei brucei and matched controls using semi-quantitative end-point RT-PCR. Levels of CXCL10 in the serum and cerebrospinal fluid were determined using ELISA. Sleep/wake states were monitored by telemetric recording. Using immunohistochemistry, parasites were found in the brain parenchyma at 14 days post-infection (dpi), but not at 6 dpi. Ifn-γ, Cxcl9, Cxcl10 and Cxcl11 mRNA levels showed moderate upregulation by 14 dpi followed by further increase between 14 and 21 dpi. CXCL10 concentration in the cerebrospinal fluid increased between 14 and 21 dpi, preceded by a rise in the serum CXCL10 level between 6 and 14 dpi. Sleep/wake pattern fragmentation was evident at 14 dpi, especially in the phase of wake predominance, with intrusion of sleep episodes into wakefulness. The results show a modest increase in Cxcl9 and Cxcl11 transcripts in the brain and the emergence of sleep/wake cycle fragmentation in the initial encephalitic stage, followed by increases in Ifn-γ and IFN-dependent chemokine transcripts in the brain and of CXCL10 in the cerebrospinal fluid. The latter parameter and sleep/wake alterations could provide combined humoral and functional biomarkers of the early encephalitic stage in African trypanosomiasis.

  18. Sleep Apnea (For Parents)

    Science.gov (United States)

    ... Braces Eating Disorders Mitral Valve Prolapse Arrhythmias Obstructive Sleep Apnea KidsHealth > For Parents > Obstructive Sleep Apnea Print ... kids and teens can develop it, too. About Sleep Apnea Sleep apnea happens when a person stops ...

  19. Pediatric sleep apnea

    Science.gov (United States)

    Sleep apnea - pediatric; Apnea - pediatric sleep apnea syndrome; Sleep-disordered breathing - pediatric ... During sleep, all of the muscles in the body become more relaxed. This includes the muscles that help keep ...

  20. Obstructive sleep apnea - adults

    Science.gov (United States)

    Sleep apnea - obstructive - adults; Apnea - obstructive sleep apnea syndrome - adults; Sleep-disordered breathing - adults; OSA - adults ... When you sleep, all of the muscles in your body become more relaxed. This includes the muscles that help keep your ...

  1. Advances in Sleep Studies

    Science.gov (United States)

    ... page please turn JavaScript on. Feature: Sleep Disorders Advances in Sleep Studies Past Issues / Summer 2015 Table ... Disorders / Tips for Getting A Good Night's Sleep / Advances In Sleep Studies Summer 2015 Issue: Volume 10 ...

  2. What Are Sleep Studies?

    Science.gov (United States)

    ... Sleep Studies Related Topics CPAP Narcolepsy Sleep Apnea Sleep Deprivation and Deficiency Send a link to NHLBI to ... away after they are removed. Your doctor will review your sleep study test results and develop a treatment plan ...

  3. Sleep Disorders (PDQ)

    Science.gov (United States)

    ... Sleep disorders are more common in people with cancer. While sleep disorders affect a small number of healthy people, as many as half of patients with cancer have problems sleeping. The sleep disorders ...

  4. Sleep Terrors (Night Terrors)

    Science.gov (United States)

    ... can contribute to sleep terrors, such as: Sleep deprivation and extreme tiredness Stress Sleep schedule disruptions, travel ... such as depression and anxiety In adults, alcohol use Risk factors Sleep terrors are more common if ...

  5. Sleep Problems

    Science.gov (United States)

    ... Drugs to treat Sleep Disorders Tips on using CPAP machine (video) More in For Women Medication Safety ... Emergency Preparedness International Programs News & Events Training & Continuing Education Inspections & Compliance Federal, State & Local Officials Consumers Health ...

  6. Sleep Disorders

    Science.gov (United States)

    ... sufficient to promote a normal circadian rhythm. Avoid sedentary activities during the day. Participate in activities outside ... the name. People with rapid eye movement sleep behavior disorder (RBD) do not have the normal relaxation ...

  7. Refreshing Sleep and Sleep Continuity Determine Perceived Sleep Quality

    Directory of Open Access Journals (Sweden)

    Eva Libman

    2016-01-01

    Full Text Available Sleep quality is a construct often measured, employed as an outcome criterion for therapeutic success, but never defined. In two studies we examined appraised good and poor sleep quality in three groups: a control group, individuals with obstructive sleep apnea, and those with insomnia disorder. In Study 1 we used qualitative methodology to examine good and poor sleep quality in 121 individuals. In Study 2 we examined sleep quality in 171 individuals who had not participated in Study 1 and evaluated correlates and predictors of sleep quality. Across all six samples and both qualitative and quantitative methodologies, the daytime experience of feeling refreshed (nonrefreshed in the morning and the nighttime experience of good (impaired sleep continuity characterized perceived good and poor sleep. Our results clarify sleep quality as a construct and identify refreshing sleep and sleep continuity as potential clinical and research outcome measures.

  8. Trypanosoma brucei FKBP12 differentially controls motility and cytokinesis in procyclic and bloodstream forms.

    Science.gov (United States)

    Brasseur, Anaïs; Rotureau, Brice; Vermeersch, Marjorie; Blisnick, Thierry; Salmon, Didier; Bastin, Philippe; Pays, Etienne; Vanhamme, Luc; Pérez-Morga, David

    2013-02-01

    FKBP12 proteins are able to inhibit TOR kinases or calcineurin phosphatases upon binding of rapamycin or FK506 drugs, respectively. The Trypanosoma brucei FKBP12 homologue (TbFKBP12) was found to be a cytoskeleton-associated protein with specific localization in the flagellar pocket area of the bloodstream form. In the insect procyclic form, RNA interference-mediated knockdown of TbFKBP12 affected motility. In bloodstream cells, depletion of TbFKBP12 affected cytokinesis and cytoskeleton architecture. These last effects were associated with the presence of internal translucent cavities limited by an inside-out configuration of the normal cell surface, with a luminal variant surface glycoprotein coat lined up by microtubules. These cavities, which recreated the streamlined shape of the normal trypanosome cytoskeleton, might represent unsuccessful attempts for cell abscission. We propose that TbFKBP12 differentially affects stage-specific processes through association with the cytoskeleton.

  9. Sec16 determines the size and functioning of the Golgi in the protist parasite, Trypanosoma brucei.

    Science.gov (United States)

    Sealey-Cardona, Marco; Schmidt, Katy; Demmel, Lars; Hirschmugl, Tatjana; Gesell, Tanja; Dong, Gang; Warren, Graham

    2014-06-01

    The Sec16 homologue in Trypanosoma brucei has been identified and characterized. TbSec16 colocalizes with COPII components at the single endoplasmic reticulum exit site (ERES), which is next to the single Golgi stack in the insect (procyclic) form of this organism. Depletion of TbSec16 reduces the size of the ERES and the Golgi, and slows growth and transport of a secretory marker to the cell surface; conversely, overexpression of TbSec16 increases the size of the ERES and Golgi but has no effect on growth or secretion. Together these data suggest that TbSec16 regulates the size of the ERES and Golgi and this size is set for optimal growth of the organism. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Enhanced succinic acid production in Aspergillus saccharolyticus by heterologous expression of fumarate reductase from Trypanosoma brucei

    DEFF Research Database (Denmark)

    Yang, Lei; Lübeck, Mette; Ahring, Birgitte K.

    2015-01-01

    production medium as well as the complete medium, but the measured enzyme activities were different depending on the media. Furthermore, a soluble NADH-dependent fumarate reductase gene (frd) from Trypanosoma brucei was inserted and expressed in A. saccharolyticus. The expression of the frd gene led......Aspergillus saccharolyticus exhibits great potential as a cell factory for industrial production of dicarboxylic acids. In the analysis of the organic acid profile, A. saccharolyticus was cultivated in an acid production medium using two different pH conditions. The specific activities...... on the pattern and the amount of organic acids produced by A. saccharolyticus. The wild-type strain produced higher amount of malic acid and succinic acid in the pH buffered condition (pH 6.5) compared with the pH non-buffered condition. The enzyme assays showed that the rTCA branch was active in the acid...

  11. Extracellular Vesicles from Trypanosoma brucei Mediate Virulence Factor Transfer and Cause Host Anemia.

    Science.gov (United States)

    Szempruch, Anthony J; Sykes, Steven E; Kieft, Rudo; Dennison, Lauren; Becker, Allison C; Gartrell, Anzio; Martin, William J; Nakayasu, Ernesto S; Almeida, Igor C; Hajduk, Stephen L; Harrington, John M

    2016-01-14

    Intercellular communication between parasites and with host cells provides mechanisms for parasite development, immune evasion, and disease pathology. Bloodstream African trypanosomes produce membranous nanotubes that originate from the flagellar membrane and disassociate into free extracellular vesicles (EVs). Trypanosome EVs contain several flagellar proteins that contribute to virulence, and Trypanosoma brucei rhodesiense EVs contain the serum resistance-associated protein (SRA) necessary for human infectivity. T. b. rhodesiense EVs transfer SRA to non-human infectious trypanosomes, allowing evasion of human innate immunity. Trypanosome EVs can also fuse with mammalian erythrocytes, resulting in rapid erythrocyte clearance and anemia. These data indicate that trypanosome EVs are organelles mediating non-hereditary virulence factor transfer and causing host erythrocyte remodeling, inducing anemia. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Compositional compartmentalization of the nuclear genomes of Trypanosoma brucei and Trypanosoma equiperdum.

    Science.gov (United States)

    Isacchi, A; Bernardi, G; Bernardi, G

    1993-12-06

    High molecular weight DNA preparations from Trypanosoma brucei and Trypanosoma equiperdum were fractionated by preparative centrifugation in a Cs2SO4 density gradient in the presence of BAMD, bis(acetatomercurimethyl)dioxane, a sequence-specific DNA ligand. Analytical centrifugation in CsCl of the DNA fractions so obtained showed that both DNAs had a bimodal distribution with two major peaks banding at 1.702-1.703 and 1.708 g/cm3 and representing 1/3 and 2/3 of total DNA, respectively. Several minor components were also detected. These results indicate that a compositional compartmentalization is not only found in the genome of vertebrates and plants, as already described, but also in those of protozoa such as Trypanosomes.

  13. Zinc finger nuclease technology: A stable tool for high efficiency transformation in bloodstream form T. brucei.

    Science.gov (United States)

    Schumann, Gabriela; Kangussu-Marcolino, Monica M; Doiron, Nicholas; Käser, Sandro; de Assis Burle-Caldas, Gabriela; DaRocha, Wanderson D; Teixeira, Santuza M; Roditi, Isabel

    2017-04-01

    In Trypanosoma brucei, the generation of knockout mutants is relatively easy compared to other organisms as transfection methods are well established. These methods have their limitations, however, when it comes to the generation of genome-wide libraries that require a minimum of several hundred thousand transformants. Double-strand breaks with the meganuclease ISce-I dramatically increase transformation efficiency, but are not widely in use as cell lines need to be generated de novo before each transfection. Here we show that zinc finger nucleases are a robust and stable tool that can enhance transformation in bloodstream forms by more than an order of magnitude. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Population genetics of Trypanosoma brucei rhodesiense: clonality and diversity within and between foci.

    Directory of Open Access Journals (Sweden)

    Craig W Duffy

    2013-11-01

    Full Text Available African trypanosomes are unusual among pathogenic protozoa in that they can undergo their complete morphological life cycle in the tsetse fly vector with mating as a non-obligatory part of this development. Trypanosoma brucei rhodesiense, which infects humans and livestock in East and Southern Africa, has classically been described as a host-range variant of the non-human infective Trypanosoma brucei that occurs as stable clonal lineages. We have examined T. b. rhodesiense populations from East (Uganda and Southern (Malawi Africa using a panel of microsatellite markers, incorporating both spatial and temporal analyses. Our data demonstrate that Ugandan T. b. rhodesiense existed as clonal populations, with a small number of highly related genotypes and substantial linkage disequilibrium between pairs of loci. However, these populations were not stable as the dominant genotypes changed and the genetic diversity also reduced over time. Thus these populations do not conform to one of the criteria for strict clonality, namely stability of predominant genotypes over time, and our results show that, in a period in the mid 1990s, the previously predominant genotypes were not detected but were replaced by a novel clonal population with limited genetic relationship to the original population present between 1970 and 1990. In contrast, the Malawi T. b. rhodesiense population demonstrated significantly greater diversity and evidence for frequent genetic exchange. Therefore, the population genetics of T. b. rhodesiense is more complex than previously described. This has important implications for the spread of the single copy T. b. rhodesiense gene that allows human infectivity, and therefore the epidemiology of the human disease, as well as suggesting that these parasites represent an important organism to study the influence of optional recombination upon population genetic dynamics.

  15. Secondary Metabolites from Vietnamese Marine Invertebrates with Activity against Trypanosoma brucei and T. cruzi

    Directory of Open Access Journals (Sweden)

    Nguyen Phuong Thao

    2014-06-01

    Full Text Available Marine-derived natural products from invertebrates comprise an extremely diverse and promising source of the compounds from a wide variety of structural classes. This study describes the discovery of five marine natural products with activity against Trypanosoma species by natural product library screening using whole cell in vitro assays. We investigated the anti-trypanosomal activity of the extracts from the soft corals and echinoderms living in Vietnamese seas. Of the samples screened, the methanolic extracts of several marine organisms exhibited potent activities against cultures of Trypanosoma brucei and T. cruzi (EC50 < 5.0 μg/mL. Among the compounds isolated from these extracts, laevigatol B (1 from Lobophytum crassum and L. laevigatum, (24S-ergost-4-ene-3-one (2 from Sinularia dissecta, astropectenol A (3 from Astropecten polyacanthus, and cholest-8-ene-3β,5α,6β,7α-tetraol (4 from Diadema savignyi showed inhibitory activity against T. brucei with EC50 values ranging from 1.57 ± 0.14 to 14.6 ± 1.36 μM, relative to the positive control, pentamidine (EC50 = 0.015 ± 0.003 μM. Laevigatol B (1 and 5α-cholest-8(14-ene-3β,7α-diol (5 exhibited also significant inhibitory effects on T. cruzi. The cytotoxic activity of the pure compounds on mammalian cells was also assessed and found to be insignificant in all cases. This is the first report on the inhibitory effects of marine organisms collected in Vietnamese seas against Trypanosoma species responsible for neglected tropical diseases.

  16. Sleep Tips: 7 Steps to Better Sleep

    Science.gov (United States)

    ... turn every night. Consider simple tips for better sleep, from setting a sleep schedule to including physical activity in your daily ... factors that can interfere with a good night's sleep — from work stress and family responsibilities to unexpected ...

  17. African Trypanosomiasis

    Science.gov (United States)

    2011-06-01

    human tissue. Trypanosoma brucei gambiense can infect domestic an- imals such as pigs , goats, and sheep, but humans are the most significant host.17...also serve as hosts. Trypanosomes can cross the placenta and infect the fetus, causing abortion, stillbirth, or neonatal death.18 They are rarely...in the liver. Trypanosomes escape the host immune response by a variety of mechanisms.29 Trypanosoma brucei gambiense and T. b. rhodesiense evade

  18. Sleep in Othello

    OpenAIRE

    Dimsdale, Joel E.

    2009-01-01

    Some of our best descriptions of sleep disorders come from literature. While Shakespeare is well known for his references to insomnia and sleep walking, his works also demonstrate a keen awareness of many other sleep disorders. This paper examines sleep themes in Shakespeare's play Othello. The play indicates Shakespeare's astute eye for sleep deprivation, sexual parasomnias, and effects of stress and drugs on sleep.

  19. Sleep quality, sleep propensity and academic performance.

    Science.gov (United States)

    Howell, Andrew J; Jahrig, Jesse C; Powell, Russell A

    2004-10-01

    We examined associations between measures of sleep propensity on the Epworth Sleepiness Scale, sleep quality on the Pittsburgh Sleep Quality Index and academic performance by GPA and grades in introductory psychology for 414 students. In the total sample, neither sleep propensity nor sleep quality correlated with GPA or introductory psychology grades. However, among students carrying a full course load, those reporting poor sleep quality performed less well on academic measures than those reporting a better quality of sleep. Further research is needed to assess the moderating influence of overall demands of daytime functioning on the association between sleep quality and academic performance.

  20. No gold standard estimation of the sensitivity and specificity of two molecular diagnostic protocols for Trypanosoma brucei spp. in Western Kenya.

    Directory of Open Access Journals (Sweden)

    Barend Mark de Clare Bronsvoort

    2010-01-01

    Full Text Available African animal trypanosomiasis is caused by a range of tsetse transmitted protozoan parasites includingTrypanosoma vivax, Trypanosoma congolense and Trypansoma brucei. In Western Kenya and other parts of East Africa two subspecies of T. brucei, T.b. brucei and the zoonoticT.b. rhodesiense, co-circulate in livestock. A range of polymerase chain reactions (PCR have been developed as important molecular diagnostic tools for epidemiological investigations of T. brucei s.l. in the animal reservoir and of its zoonotic potential. Quantification of the relative performance of different diagnostic PCRs is essential to ensure comparability of studies. This paper describes an evaluation of two diagnostic test systems for T. brucei using a T. brucei s.l. specific PCR [1] and a single nested PCR targeting the Internal Transcribed Spacer (ITS regions of trypanosome ribosomal DNA [2]. A Bayesian formulation of the Hui-Walter latent class model was employed to estimate their test performance in the absence of a gold standard test for detecting T.brucei s.l. infections in ear-vein blood samples from cattle, pig, sheep and goat populations in Western Kenya, stored on Whatman FTA cards. The results indicate that the system employing the T. brucei s.l. specific PCR (Se1=0.760 had a higher sensitivity than the ITS-PCR (Se2=0.640; both have high specificity (Sp1=0.998; Sp2=0.997. The true prevalences for livestock populations were estimated (pcattle=0.091, ppigs=0.066, pgoats=0.005, psheep=0.006, taking into account the uncertainties in the specificity and sensitivity of the two test systems. Implications of test performance include the required survey sample size; due to its higher sensitivity and specificity, the T. brucei s.l. specific PCR requires a consistently smaller sample size than the ITS-PCR for the detection of T. brucei s.l. However the ITS-PCR is able to simultaneously screen samples for other pathogenic trypanosomes and may thus be, overall, a better

  1. Refreshing Sleep and Sleep Continuity Determine Perceived Sleep Quality

    OpenAIRE

    Eva Libman; Catherine Fichten; Laura Creti; Kerry Conrod; Dieu-Ly Tran; Roland Grad; Mary Jorgensen; Rhonda Amsel; Dorrie Rizzo; Marc Baltzan; Alan Pavilanis; Sally Bailes

    2016-01-01

    Sleep quality is a construct often measured, employed as an outcome criterion for therapeutic success, but never defined. In two studies we examined appraised good and poor sleep quality in three groups: a control group, individuals with obstructive sleep apnea, and those with insomnia disorder. In Study 1 we used qualitative methodology to examine good and poor sleep quality in 121 individuals. In Study 2 we examined sleep quality in 171 individuals who had not participated in Study 1 and ev...

  2. T. brucei infection reduces B lymphopoiesis in bone marrow and truncates compensatory splenic lymphopoiesis through transitional B-cell apoptosis.

    Directory of Open Access Journals (Sweden)

    Viki Bockstal

    2011-06-01

    Full Text Available African trypanosomes of the Trypanosoma brucei species are extracellular protozoan parasites that cause the deadly disease African trypanosomiasis in humans and contribute to the animal counterpart, Nagana. Trypanosome clearance from the bloodstream is mediated by antibodies specific for their Variant Surface Glycoprotein (VSG coat antigens. However, T. brucei infection induces polyclonal B cell activation, B cell clonal exhaustion, sustained depletion of mature splenic Marginal Zone B (MZB and Follicular B (FoB cells, and destruction of the B-cell memory compartment. To determine how trypanosome infection compromises the humoral immune defense system we used a C57BL/6 T. brucei AnTat 1.1 mouse model and multicolor flow cytometry to document B cell development and maturation during infection. Our results show a more than 95% reduction in B cell precursor numbers from the CLP, pre-pro-B, pro-B, pre-B and immature B cell stages in the bone marrow. In the spleen, T. brucei induces extramedullary B lymphopoiesis as evidenced by significant increases in HSC-LMPP, CLP, pre-pro-B, pro-B and pre-B cell populations. However, final B cell maturation is abrogated by infection-induced apoptosis of transitional B cells of both the T1 and T2 populations which is not uniquely dependent on TNF-, Fas-, or prostaglandin-dependent death pathways. Results obtained from ex vivo co-cultures of living bloodstream form trypanosomes and splenocytes demonstrate that trypanosome surface coat-dependent contact with T1/2 B cells triggers their deletion. We conclude that infection-induced and possibly parasite-contact dependent deletion of transitional B cells prevents replenishment of mature B cell compartments during infection thus contributing to a loss of the host's capacity to sustain antibody responses against recurring parasitemic waves.

  3. Apocytochrome b and other mitochondrial DNA sequences are differentially expressed during the life cycle of Trypanosoma brucei.

    OpenAIRE

    Feagin, J E; Jasmer, D P; Stuart, K

    1985-01-01

    Cytochromes and Krebs cycle enzymes are not detected in bloodstream forms of Trypanosoma brucei but are present in procyclic forms. We have analyzed transcription of mitochondrial sequences which contain the apocytochrome b gene and several other open reading frames (ORFs). Multiple transcripts map to individual DNA sequences located on both DNA strands. Larger low abundance transcripts map to multiple ORFs and may be precursor RNAs. Small abundant transcripts map to G + C rich sequences that...

  4. A target-based high throughput screen yields Trypanosoma brucei hexokinase small molecule inhibitors with antiparasitic activity.

    Directory of Open Access Journals (Sweden)

    Elizabeth R Sharlow

    2010-04-01

    Full Text Available The parasitic protozoan Trypanosoma brucei utilizes glycolysis exclusively for ATP production during infection of the mammalian host. The first step in this metabolic pathway is mediated by hexokinase (TbHK, an enzyme essential to the parasite that transfers the gamma-phospho of ATP to a hexose. Here we describe the identification and confirmation of novel small molecule inhibitors of bacterially expressed TbHK1, one of two TbHKs expressed by T. brucei, using a high throughput screening assay.Exploiting optimized high throughput screening assay procedures, we interrogated 220,233 unique compounds and identified 239 active compounds from which ten small molecules were further characterized. Computation chemical cluster analyses indicated that six compounds were structurally related while the remaining four compounds were classified as unrelated or singletons. All ten compounds were approximately 20-17,000-fold more potent than lonidamine, a previously identified TbHK1 inhibitor. Seven compounds inhibited T. brucei blood stage form parasite growth (0.03brucei parasites, Leishmania promastigotes, and mammalian cell lines. Analysis of two structurally related compounds, ebselen and SID 17387000, revealed that both were mixed inhibitors of TbHK1 with respect to ATP. Additionally, both compounds inhibited parasite lysate-derived HK activity. None of the compounds displayed structural similarity to known hexokinase inhibitors or human African trypanosomiasis therapeutics.The novel chemotypes identified here could represent leads for future therapeutic development against the African trypanosome.

  5. New discoveries in the transmission biology of sleeping sickness parasites: applying the basics.

    Science.gov (United States)

    MacGregor, Paula; Matthews, Keith R

    2010-09-01

    The sleeping sickness parasite, Trypanosoma brucei, must differentiate in response to the changing environments that it encounters during its complex life cycle. One developmental form, the bloodstream stumpy stage, plays an important role in infection dynamics and transmission of the parasite. Recent advances have shed light on the molecular mechanisms by which these stumpy forms differentiate as they are transmitted from the mammalian host to the insect vector of sleeping sickness, tsetse flies. These molecular advances now provide improved experimental tools for the study of stumpy formation and function within the mammalian bloodstream. They also offer new routes to therapy via high-throughput screens for agents that accelerate parasite development. Here, we shall discuss the recent advances that have been made and the prospects for future research now available.

  6. Channel-forming activities in the glycosomal fraction from the bloodstream form of Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Melisa Gualdron-López

    Full Text Available BACKGROUND: Glycosomes are a specialized form of peroxisomes (microbodies present in unicellular eukaryotes that belong to the Kinetoplastea order, such as Trypanosoma and Leishmania species, parasitic protists causing severe diseases of livestock and humans in subtropical and tropical countries. The organelles harbour most enzymes of the glycolytic pathway that is responsible for substrate-level ATP production in the cell. Glycolysis is essential for bloodstream-form Trypanosoma brucei and enzymes comprising this pathway have been validated as drug targets. Glycosomes are surrounded by a single membrane. How glycolytic metabolites are transported across the glycosomal membrane is unclear. METHODS/PRINCIPAL FINDINGS: We hypothesized that glycosomal membrane, similarly to membranes of yeast and mammalian peroxisomes, contains channel-forming proteins involved in the selective transfer of metabolites. To verify this prediction, we isolated a glycosomal fraction from bloodstream-form T. brucei and reconstituted solubilized membrane proteins into planar lipid bilayers. The electrophysiological characteristics of the channels were studied using multiple channel recording and single channel analysis. Three main channel-forming activities were detected with current amplitudes 70-80 pA, 20-25 pA, and 8-11 pA, respectively (holding potential +10 mV and 3.0 M KCl as an electrolyte. All channels were in fully open state in a range of voltages ±150 mV and showed no sub-conductance transitions. The channel with current amplitude 20-25 pA is anion-selective (P(K+/P(Cl-∼0.31, while the other two types of channels are slightly selective for cations (P(K+/P(Cl- ratios ∼1.15 and ∼1.27 for the high- and low-conductance channels, respectively. The anion-selective channel showed an intrinsic current rectification that may suggest a functional asymmetry of the channel's pore. CONCLUSIONS/SIGNIFICANCE: These results indicate that the membrane of glycosomes

  7. Sleep patterns and sleep disturbances across pregnancy.

    Science.gov (United States)

    Mindell, Jodi A; Cook, Rae Ann; Nikolovski, Janeta

    2015-04-01

    This study sought to characterize sleep patterns and sleep problems in a large sample of women across all months of pregnancy. A total of 2427 women completed an Internet-based survey that included the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale, vitality scale of the Short Form 36 Health Survey (SF-36), Insomnia Severity Index (ISI), Berlin questionnaire, International Restless Legs Syndrome (IRLS) question set, and a short version of the Pregnancy Symptoms Inventory (PSI). Across all months of pregnancy, women experienced poor sleep quality (76%), insufficient nighttime sleep (38%), and significant daytime sleepiness (49%). All women reported frequent nighttime awakenings (100%), and most women took daytime naps (78%). Symptoms of insomnia (57%), sleep-disordered breathing (19%), and restless legs syndrome (24%) were commonly endorsed, with no difference across the month of pregnancy for insomnia, sleep-disorder breathing, daytime sleepiness, or fatigue. In addition, high rates of pregnancy-related symptoms were found to disturb sleep, especially frequent urination (83%) and difficulty finding a comfortable sleep position (79%). Women experience significant sleep disruption, inadequate sleep, and high rates of symptoms of sleep disorder throughout pregnancy. These results suggest that all women should be screened and treated for sleep disturbances throughout pregnancy, especially given the impact of inadequate sleep and sleep disorders on fetal, pregnancy, and postpartum outcomes. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Polysomes of Trypanosoma brucei: Association with Initiation Factors and RNA-Binding Proteins.

    Directory of Open Access Journals (Sweden)

    Cornelia Klein

    Full Text Available We report here the results of experiments designed to identify RNA-binding proteins that might be associated with Trypanosoma brucei polysomes. After some preliminary mass spectrometry of polysomal fractions, we investigated the distributions of selected tagged proteins using sucrose gradients and immunofluorescence. As expected, the polysomal fractions contained nearly all annotated ribosomal proteins, the translation-associated protein folding complex, and many translation factors, but also many other abundant proteins. Results suggested that cap-binding proteins EIF4E3 and EIF4E4 were associated with both free and membrane-bound polysomes. The EIF4E binding partners EIF4G4 and EIF4G3 were present but the other EIF4E and EIF4G paralogues were not detected. The dominant EIF4E in the polysomal fraction is EIF4E4 and very few polysomal mRNAs are associated with EIF4G. Thirteen potential mRNA-binding proteins were detected in the polysomes, including the known polysome-associated protein RBP42. The locations of two of the other proteins were tested after epitope tagging: RBP29 was in the nucleus and ZC3H29 was in the cytoplasm. Quantitative analyses showed that specific association of an RNA-binding protein with the polysome fraction in sucrose gradients will not be detected if the protein is in more than 25-fold molar excess over its target binding sites.

  9. Dynamic modelling under uncertainty: the case of Trypanosoma brucei energy metabolism.

    Directory of Open Access Journals (Sweden)

    Fiona Achcar

    2012-01-01

    Full Text Available Kinetic models of metabolism require detailed knowledge of kinetic parameters. However, due to measurement errors or lack of data this knowledge is often uncertain. The model of glycolysis in the parasitic protozoan Trypanosoma brucei is a particularly well analysed example of a quantitative metabolic model, but so far it has been studied with a fixed set of parameters only. Here we evaluate the effect of parameter uncertainty. In order to define probability distributions for each parameter, information about the experimental sources and confidence intervals for all parameters were collected. We created a wiki-based website dedicated to the detailed documentation of this information: the SilicoTryp wiki (http://silicotryp.ibls.gla.ac.uk/wiki/Glycolysis. Using information collected in the wiki, we then assigned probability distributions to all parameters of the model. This allowed us to sample sets of alternative models, accurately representing our degree of uncertainty. Some properties of the model, such as the repartition of the glycolytic flux between the glycerol and pyruvate producing branches, are robust to these uncertainties. However, our analysis also allowed us to identify fragilities of the model leading to the accumulation of 3-phosphoglycerate and/or pyruvate. The analysis of the control coefficients revealed the importance of taking into account the uncertainties about the parameters, as the ranking of the reactions can be greatly affected. This work will now form the basis for a comprehensive Bayesian analysis and extension of the model considering alternative topologies.

  10. Functional analysis of TOEFAZ1 uncovers protein domains essential for cytokinesis in Trypanosoma brucei.

    Science.gov (United States)

    Sinclair-Davis, Amy N; McAllaster, Michael R; de Graffenried, Christopher L

    2017-10-09

    The parasite Trypanosoma brucei is highly polarized, including a flagellum that is attached along the cell surface by the flagellum attachment zone (FAZ). During cell division, the new FAZ positions the cleavage furrow, which ingresses from the anterior tip of the cell towards the posterior. We recently identified Tip Of the Extending FAZ protein 1 (TOEFAZ1) as an essential protein in trypanosome cytokinesis. We analyzed the localization and function of TOEFAZ1 domains using overexpression and RNAi complementation. TOEFAZ1 comprises three domains with separable functions: an N-terminal α-helical domain that may be involved in FAZ recruitment, a central intrinsically disordered domain that retains the morphogenic kinase TbPLK at the new FAZ tip, and a C-terminal zinc finger domain necessary for TOEFAZ1 oligomerization. Both the N-terminal and C-terminal domains are essential for TOEFAZ1 function, but TbPLK retention at the FAZ is not necessary for cytokinesis. The feasibility of alternate cytokinetic pathways that do not employ TOEFAZ1 are also assessed. Our results show that TOEFAZ1 is a multimeric scaffold for recruiting proteins that control the timing and location of cleavage furrow ingression. © 2017. Published by The Company of Biologists Ltd.

  11. Spliced leader trapping reveals widespread alternative splicing patterns in the highly dynamic transcriptome of Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Daniel Nilsson

    2010-08-01

    Full Text Available Trans-splicing of leader sequences onto the 5'ends of mRNAs is a widespread phenomenon in protozoa, nematodes and some chordates. Using parallel sequencing we have developed a method to simultaneously map 5'splice sites and analyze the corresponding gene expression profile, that we term spliced leader trapping (SLT. The method can be applied to any organism with a sequenced genome and trans-splicing of a conserved leader sequence. We analyzed the expression profiles and splicing patterns of bloodstream and insect forms of the parasite Trypanosoma brucei. We detected the 5' splice sites of 85% of the annotated protein-coding genes and, contrary to previous reports, found up to 40% of transcripts to be differentially expressed. Furthermore, we discovered more than 2500 alternative splicing events, many of which appear to be stage-regulated. Based on our findings we hypothesize that alternatively spliced transcripts present a new means of regulating gene expression and could potentially contribute to protein diversity in the parasite. The entire dataset can be accessed online at TriTrypDB or through: http://splicer.unibe.ch/.

  12. Isothermal microcalorimetry, a new tool to monitor drug action against Trypanosoma brucei and Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Tanja Wenzler

    Full Text Available Isothermal microcalorimetry is an established tool to measure heat flow of physical, chemical or biological processes. The metabolism of viable cells produces heat, and if sufficient cells are present, their heat production can be assessed by this method. In this study, we investigated the heat flow of two medically important protozoans, Trypanosoma brucei rhodesiense and Plasmodium falciparum. Heat flow signals obtained for these pathogens allowed us to monitor parasite growth on a real-time basis as the signals correlated with the number of viable cells. To showcase the potential of microcalorimetry for measuring drug action on pathogenic organisms, we tested the method with three antitrypanosomal drugs, melarsoprol, suramin and pentamidine and three antiplasmodial drugs, chloroquine, artemether and dihydroartemisinin, each at two concentrations on the respective parasite. With the real time measurement, inhibition was observed immediately by a reduced heat flow compared to that in untreated control samples. The onset of drug action, the degree of inhibition and the time to death of the parasite culture could conveniently be monitored over several days. Microcalorimetry is a valuable element to be added to the toolbox for drug discovery for protozoal diseases such as human African trypanosomiasis and malaria. The method could probably be adapted to other protozoan parasites, especially those growing extracellularly.

  13. Flux Analysis of the Trypanosoma brucei Glycolysis Based on a Multiobjective-Criteria Bioinformatic Approach

    Directory of Open Access Journals (Sweden)

    Amine Ghozlane

    2012-01-01

    Full Text Available Trypanosoma brucei is a protozoan parasite of major of interest in discovering new genes for drug targets. This parasite alternates its life cycle between the mammal host(s (bloodstream form and the insect vector (procyclic form, with two divergent glucose metabolism amenable to in vitro culture. While the metabolic network of the bloodstream forms has been well characterized, the flux distribution between the different branches of the glucose metabolic network in the procyclic form has not been addressed so far. We present a computational analysis (called Metaboflux that exploits the metabolic topology of the procyclic form, and allows the incorporation of multipurpose experimental data to increase the biological relevance of the model. The alternatives resulting from the structural complexity of networks are formulated as an optimization problem solved by a metaheuristic where experimental data are modeled in a multiobjective function. Our results show that the current metabolic model is in agreement with experimental data and confirms the observed high metabolic flexibility of glucose metabolism. In addition, Metaboflux offers a rational explanation for the high flexibility in the ratio between final products from glucose metabolism, thsat is, flux redistribution through the malic enzyme steps.

  14. A transcription-independent epigenetic mechanism is associated with antigenic switching in Trypanosoma brucei.

    Science.gov (United States)

    Aresta-Branco, Francisco; Pimenta, Silvia; Figueiredo, Luisa M

    2016-04-20

    Antigenic variation in Trypanosoma brucei relies on periodic switching of variant surface glycoproteins (VSGs), which are transcribed monoallelically by RNA polymerase I from one of about 15 bloodstream expression sites (BES). Chromatin of the actively transcribed BES is depleted of nucleosomes, but it is unclear if this open conformation is a mere consequence of a high rate of transcription, or whether it is maintained by a transcription-independent mechanism. Using an inducible BES-silencing reporter strain, we observed that chromatin of the active BES remains open for at least 24 hours after blocking transcription. This conformation is independent of the cell-cycle stage, but dependent upon TDP1, a high mobility group box protein. For two days after BES silencing, we detected a transient and reversible derepression of several silent BESs within the population, suggesting that cells probe other BESs before commitment to one, which is complete by 48 hours. FACS sorting and subsequent subcloning confirmed that probing cells are switching intermediates capable of returning to the original BES, switch to the probed BES or to a different BES. We propose that regulation of BES chromatin structure is an epigenetic mechanism important for successful antigenic switching. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. Duplicated paralogous genes subject to positive selection in the genome of Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Richard D Emes

    2008-05-01

    Full Text Available Whole genome studies have highlighted duplicated genes as important substrates for adaptive evolution. We have investigated adaptive evolution in this class of genes in the human parasite Trypanosoma brucei, as indicated by the ratio of non-synonymous (amino-acid changing to synonymous (amino acid retaining nucleotide substitution rates.We have identified duplicated genes that are most rapidly evolving in this important human parasite. This is the first attempt to investigate adaptive evolution in this species at the codon level. We identify 109 genes within 23 clusters of paralogous gene expansions to be subject to positive selection.Genes identified include surface antigens in both the mammalian and insect host life cycle stage suggesting that competitive interaction is not solely with the adaptive immune system of the mammalian host. Also surface transporters related to drug resistance and genes related to developmental progression are detected. We discuss how adaptive evolution of these genes may highlight lineage specific processes essential for parasite survival. We also discuss the implications of adaptive evolution of these targets for parasite biology and control.

  16. Strategies for Getting Enough Sleep

    Science.gov (United States)

    ... the NHLBI on Twitter. Strategies for Getting Enough Sleep You can take steps to improve your sleep ... Rate This Content: NEXT >> Updated: June 7, 2017 Sleep Infographic Sleep Disorders & Insufficient Sleep: Improving Health through ...

  17. How Much Sleep Is Enough

    Science.gov (United States)

    ... June 7, 2017 Sleep Infographic Sleep Disorders & Insufficient Sleep: Improving Health through Research National Institutes of Health- (NIH) supported research is shedding light on how sleep and lack of sleep affect the human body. ...

  18. Snoring and Sleep Apnea

    Science.gov (United States)

    ... dentist, or oral surgeon with expertise in sleep dentistry. In some patients, significant weight loss can also ... Link: Treatment Options for Adults with Snoring Link: Pediatric Sleep Disordered Breathing/Obstructive Sleep Apnea Link: Pediatric ...

  19. Side Effects: Sleep Problems

    Science.gov (United States)

    Sleep problems are a common side effect during cancer treatment. Learn how a polysomnogram can assess sleep problems. Learn about the benefits of managing sleep disorders in men and women with cancer.

  20. Sleep and Chronic Disease

    Science.gov (United States)

    ... Search The CDC Cancel Submit Search The CDC Sleep and Sleep Disorders Note: Javascript is disabled or is not ... Data Source Projects and Partners Resources For Clinicians Sleep and Chronic Disease Recommend on Facebook Tweet Share ...

  1. Sleep and your health

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000871.htm Sleep and your health To use the sharing features ... in a number of ways. Why You Need Sleep Sleep gives your body and brain time to ...

  2. Sleep Apnea Information Page

    Science.gov (United States)

    ... Page You are here Home » Disorders » All Disorders Sleep Apnea Information Page Sleep Apnea Information Page What research is being done? ... Institutes of Health (NIH) conduct research related to sleep apnea in laboratories at the NIH, and also ...

  3. Sleep and Newborns

    Science.gov (United States)

    ... of Braces Eating Disorders Mitral Valve Prolapse Arrhythmias Sleep and Newborns KidsHealth > For Parents > Sleep and Newborns ... night it is. How Long Will My Newborn Sleep? Newborns should get 14 to 17 hours of ...

  4. Sleep paralysis and psychopathology

    African Journals Online (AJOL)

    hypnagogic paralysis) or from sleep to wakefulness. (hypnopompic paralysis). It is considered to be a parasomnia related to rapid eye movement (REM) sleep because it tends to occur during awakenings from REM sleep and its pathophysiology.

  5. Irregular sleep (image)

    Science.gov (United States)

    ... sleep and wakefulness which disrupt the normal daily sleep-wake cycle. It may be caused by brain dysfunction or not following a normal sleep schedule, ultimately leading to a pattern of insomnia ...

  6. What Is Sleep Apnea?

    Science.gov (United States)

    ... have type 2 diabetes. Hormonal changes in sleep deprivation. We know that sleep deprivation decreases the response of the body to insulin , ... with sleep apnea who finds it hard to use your CPAP machine? This study is assessing whether ...

  7. Brain Basics: Understanding Sleep

    Science.gov (United States)

    ... and more deeply after a period of sleep deprivation. Factors that influence your sleep-wake needs include ... noise, produce light that stimulates melatonin production, and use gentle vibrations to help us sleep and wake. ...

  8. Sleep Medicine Textbook

    OpenAIRE

    Bassetti, Claudio; Dogas, Zoran; Peigneux, Philippe

    2014-01-01

    The Sleep Medicine Textbook provides comprehensive, all-in-one educational material (550 pages) structured around the Catalogue of knowledge and skills for sleep medicine (Penzel et al. 2014, Journal of Sleep Research). Written by experts in the field and published by the ESRS, it provides an European approach to sleep medicine education, and represents the knowledge-base for the ESRS-endorsed sleep medicine examinations.The book is available at http://www.esrs.eu/esrs/sleep-medicine-textbook...

  9. Further evidence from SSCP and ITS DNA sequencing support Trypanosoma evansi and Trypanosoma equiperdum as subspecies or even strains of Trypanosoma brucei.

    Science.gov (United States)

    Wen, Yan-Zi; Lun, Zhao-Rong; Zhu, Xing-Quan; Hide, Geoff; Lai, De-Hua

    2016-07-01

    The subgenus Trypanozoon includes three species Trypanosoma brucei, Trypanosoma evansi and Trypanosoma equiperdum, which are morphologically identical and indistinguishable even using some molecular methods. In this study, PCR-based single strand conformation polymorphism (PCR-SSCP) was used to analyze the ribosomal DNA of the Trypanozoon species. Data indicate different patterns of ITS2 fragments between T. brucei, T. evansi and T. equiperdum by SSCP. Furthermore, analysis of total ITS sequences within these three members of the subgenus Trypanozoon showed a high degree of homology using phylogenetic analysis but were polyphyletic in haplotype networks. These data provide novel nuclear evidence to further support the notion that T. evansi and T. equiperdum should be subspecies or even strains of T. brucei. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Energy expenditure during sleep, sleep deprivation and sleep following sleep deprivation in adult humans

    OpenAIRE

    Jung, Christopher M.; Melanson, Edward L.; Frydendall, Emily J; Perreault, Leigh; Robert H Eckel; Wright, Kenneth P.

    2010-01-01

    Sleep has been proposed to be a physiological adaptation to conserve energy, but little research has examined this proposed function of sleep in humans. We quantified effects of sleep, sleep deprivation and recovery sleep on whole-body total daily energy expenditure (EE) and on EE during the habitual day and nighttime. We also determined effects of sleep stage during baseline and recovery sleep on EE. Seven healthy participants aged 22 ± 5 years (mean ± s.d.) maintained ∼8 h per night sleep s...

  11. Sleep Disturbances in Depression.

    Science.gov (United States)

    Murphy, Michael J; Peterson, Michael J

    2015-03-01

    Major depressive disorder is frequently accompanied by sleep disturbances such as insomnia or hypersomnia and polysomnographic sleep findings of increased rapid-eye-movement sleep and decreased slow wave sleep. For many patients, insomnia persists even after mood symptoms have been adequately treated. These patients have poorer outcomes than patients without sleep problems. These outcomes suggest that overlapping neural mechanisms regulate sleep and mood. Treatment of these patients can incorporate sedating antidepressants, nonbenzodiazepine γ-aminobutyric acid agonists, and cognitive behavioral therapy. Sleep restriction has been found to improve mood in depressed patients; however, the benefits typically disappear after recovery sleep. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Atypical human infections by animal trypanosomes.

    Directory of Open Access Journals (Sweden)

    Philippe Truc

    Full Text Available The two classical forms of human trypanosomoses are sleeping sickness due to Trypanosoma brucei gambiense or T. brucei rhodesiense, and Chagas disease due to T. cruzi. However, a number of atypical human infections caused by other T. species (or sub-species have been reported, namely due to T. brucei brucei, T. vivax, T. congolense, T. evansi, T. lewisi, and T. lewisi-like. These cases are reviewed here. Some infections were transient in nature, while others required treatments that were successful in most cases, although two cases were fatal. A recent case of infection due to T. evansi was related to a lack of apolipoprotein L-I, but T. lewisi infections were not related to immunosuppression or specific human genetic profiles. Out of 19 patients, eight were confirmed between 1974 and 2010, thanks to improved molecular techniques. However, the number of cases of atypical human trypanosomoses might be underestimated. Thus, improvement, evaluation of new diagnostic tests, and field investigations are required for detection and confirmation of these atypical cases.

  13. Sleep Pharmacogenetics: Personalized Sleep-Wake Therapy.

    Science.gov (United States)

    Holst, Sebastian C; Valomon, Amandine; Landolt, Hans-Peter

    2016-01-01

    Research spanning (genetically engineered) animal models, healthy volunteers, and sleep-disordered patients has identified the neurotransmitters and neuromodulators dopamine, serotonin, norepinephrine, histamine, hypocretin, melatonin, glutamate, acetylcholine, γ-amino-butyric acid, and adenosine as important players in the regulation and maintenance of sleep-wake-dependent changes in neuronal activity and the sleep-wake continuum. Dysregulation of these neurochemical systems leads to sleep-wake disorders. Most currently available pharmacological treatments are symptomatic rather than causal, and their beneficial and adverse effects are often variable and in part genetically determined. To evaluate opportunities for evidence-based personalized medicine with present and future sleep-wake therapeutics, we review here the impact of known genetic variants affecting exposure of and sensitivity to drugs targeting the neurochemistry of sleep-wake regulation and the pathophysiology of sleep-wake disturbances. Many functional polymorphisms modify drug response phenotypes relevant for sleep. To corroborate the importance of these and newly identified variants for personalized sleep-wake therapy, human sleep pharmacogenetics should be complemented with pharmacogenomic investigations, research about sleep-wake-dependent pharmacological actions, and studies in mice lacking specific genes. These strategies, together with future knowledge about epigenetic mechanisms affecting sleep-wake physiology and treatment outcomes, may lead to potent and safe novel therapies for the increasing number of sleep-disordered patients (e.g., in aged populations).

  14. Sleep: A Health Imperative

    Science.gov (United States)

    Luyster, Faith S.; Strollo, Patrick J.; Zee, Phyllis C.; Walsh, James K.

    2012-01-01

    Chronic sleep deficiency, defined as a state of inadequate or mistimed sleep, is a growing and underappreciated determinant of health status. Sleep deprivation contributes to a number of molecular, immune, and neural changes that play a role in disease development, independent of primary sleep disorders. These changes in biological processes in response to chronic sleep deficiency may serve as etiological factors for the development and exacerbation of cardiovascular and metabolic diseases and, ultimately, a shortened lifespan. Sleep deprivation also results in significant impairments in cognitive and motor performance which increase the risk of motor vehicle crashes and work-related injuries and fatal accidents. The American Academy of Sleep Medicine and the Sleep Research Society have developed this statement to communicate to national health stakeholders the current knowledge which ties sufficient sleep and circadian alignment in adults to health. Citation: Luyster FS; Strollo PJ; Zee PC; Walsh JK. Sleep: a health imperative. SLEEP 2012;35(6):727-734. PMID:22654183

  15. College residential sleep environment.

    Science.gov (United States)

    Sexton-Radek, Kathy; Hartley, Andrew

    2013-12-01

    College students regularly report increased sleep disturbances as well as concomitant reductions in performance (e.g., academic grades) upon entering college. Sleep hygiene refers to healthy sleep practices that are commonly used as first interventions in sleep disturbances. One widely used practice of this sort involves arranging the sleep environment to minimize disturbances from excessive noise and light at bedtime. Communal sleep situations such as those in college residence halls do not easily support this intervention. Following several focus groups, a questionnaire was designed to gather self-reported information on sleep disturbances in a college population. The present study used The Young Adult Sleep Environment Inventory (YASEI) and sleep logs to investigate the sleep environment of college students living in residential halls. A summary of responses indicated that noise and light are significant sleep disturbances in these environments. Recommendations are presented related to these findings.

  16. New functions for parts of the Krebs cycle in procyclic Trypanosoma brucei, a cycle not operating as a cycle.

    Science.gov (United States)

    van Weelden, Susanne W H; van Hellemond, Jaap J; Opperdoes, Fred R; Tielens, Aloysius G M

    2005-04-01

    We investigated whether substrate availability influences the type of energy metabolism in procyclic Trypanosoma brucei. We show that absence of glycolytic substrates (glucose and glycerol) does not induce a shift from a fermentative metabolism to complete oxidation of substrates. We also show that glucose (and even glycolysis) is not essential for normal functioning and proliferation of pleomorphic procyclic T. brucei cells. Furthermore, absence of glucose did not result in increased degradation of amino acids. Variations in availability of glucose and glycerol did result, however, in adaptations in metabolism in such a way that the glycosome was always in redox balance. We argue that it is likely that, in procyclic cells, phosphoglycerate kinase is located not only in the cytosol, but also inside glycosomes, as otherwise an ATP deficit would occur in this organelle. We demonstrate that procyclic T. brucei uses parts of the Krebs cycle for purposes other than complete degradation of mitochondrial substrates. We suggest that citrate synthase plus pyruvate dehydrogenase and malate dehydrogenase are used to transport acetyl-CoA units from the mitochondrion to the cytosol for the biosynthesis of fatty acids, a process we show to occur in proliferating procyclic cells. The part of the Krebs cycle consisting of alpha-ketoglutarate dehydrogenase and succinyl-CoA synthetase was used for the degradation of proline and glutamate to succinate. We also demonstrate that the subsequent enzymes of the Krebs cycle, succinate dehydrogenase and fumarase, are most likely used for conversion of succinate into malate, which can then be used in gluconeogenesis.

  17. Trypanosoma brucei TbIF1 inhibits the essential F1-ATPase in the infectious form of the parasite.

    Directory of Open Access Journals (Sweden)

    Brian Panicucci

    2017-04-01

    Full Text Available The mitochondrial (mt FoF1-ATP synthase of the digenetic parasite, Trypanosoma brucei, generates ATP during the insect procyclic form (PF, but becomes a perpetual consumer of ATP in the mammalian bloodstream form (BF, which lacks a canonical respiratory chain. This unconventional dependence on FoF1-ATPase is required to maintain the essential mt membrane potential (Δψm. Normally, ATP hydrolysis by this rotary molecular motor is restricted to when eukaryotic cells experience sporadic hypoxic conditions, during which this compulsory function quickly depletes the cellular ATP pool. To protect against this cellular treason, the highly conserved inhibitory factor 1 (IF1 binds the enzyme in a manner that solely inhibits the hydrolytic activity. Intriguingly, we were able to identify the IF1 homolog in T. brucei (TbIF1, but determined that its expression in the mitochondrion is tightly regulated throughout the life cycle as it is only detected in PF cells. TbIF1 appears to primarily function as an emergency brake in PF cells, where it prevented the restoration of the Δψm by FoF1-ATPase when respiration was chemically inhibited. In vitro, TbIF1 overexpression specifically inhibits the hydrolytic activity but not the synthetic capability of the FoF1-ATP synthase in PF mitochondria. Furthermore, low μM amounts of recombinant TbIF1 achieve the same inhibition of total mt ATPase activity as the FoF1-ATPase specific inhibitors, azide and oligomycin. Therefore, even minimal ectopic expression of TbIF1 in BF cells proved lethal as the indispensable Δψm collapsed due to inhibited FoF1-ATPase. In summary, we provide evidence that T. brucei harbors a natural and potent unidirectional inhibitor of the vital FoF1-ATPase activity that can be exploited for future structure-based drug design.

  18. Trypanosoma brucei RAP1 maintains telomere and subtelomere integrity by suppressing TERRA and telomeric RNA:DNA hybrids.

    Science.gov (United States)

    Nanavaty, Vishal; Sandhu, Ranjodh; Jehi, Sanaa E; Pandya, Unnati M; Li, Bibo

    2017-06-02

    Trypanosoma brucei causes human African trypanosomiasis and regularly switches its major surface antigen, VSG, thereby evading the host's immune response. VSGs are monoallelically expressed from subtelomeric expression sites (ESs), and VSG switching exploits subtelomere plasticity. However, subtelomere integrity is essential for T. brucei viability. The telomeric transcript, TERRA, was detected in T. brucei previously. We now show that the active ES-adjacent telomere is transcribed. We find that TbRAP1, a telomere protein essential for VSG silencing, suppresses VSG gene conversion-mediated switching. Importantly, TbRAP1 depletion increases the TERRA level, which appears to result from longer read-through into the telomere downstream of the active ES. Depletion of TbRAP1 also results in more telomeric RNA:DNA hybrids and more double strand breaks (DSBs) at telomeres and subtelomeres. In TbRAP1-depleted cells, expression of excessive TbRNaseH1, which cleaves the RNA strand of the RNA:DNA hybrid, brought telomeric RNA:DNA hybrids, telomeric/subtelomeric DSBs and VSG switching frequency back to WT levels. Therefore, TbRAP1-regulated appropriate levels of TERRA and telomeric RNA:DNA hybrid are fundamental to subtelomere/telomere integrity. Our study revealed for the first time an important role of a long, non-coding RNA in antigenic variation and demonstrated a link between telomeric silencing and subtelomere/telomere integrity through TbRAP1-regulated telomere transcription. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Sleep for cognitive enhancement

    Directory of Open Access Journals (Sweden)

    Susanne eDiekelmann

    2014-04-01

    Full Text Available Sleep is essential for effective cognitive functioning. Loosing even a few hours of sleep can have detrimental effects on a wide variety of cognitive processes such as attention, language, reasoning, decision making, learning and memory. While sleep is necessary to ensure normal healthy cognitive functioning, it can also enhance performance beyond the boundaries of the normal condition. This article discusses the enhancing potential of sleep, mainly focusing on the domain of learning and memory. Sleep is known to facilitate the consolidation of memories learned before sleep as well as the acquisition of new memories to be learned after sleep. According to a widely held model this beneficial effect of sleep relies on the neuronal reactivation of memories during sleep that is associated with sleep-specific brain oscillations (slow oscillations, spindles, ripples as well as a characteristic neurotransmitter milieu. Recent research indicates that memory processing during sleep can be boosted by (i cueing memory reactivation during sleep, (ii stimulating sleep-specific brain oscillations, and (iii targeting specific neurotransmitter systems pharmacologically. Olfactory and auditory cues can be used, for example, to increase reactivation of associated memories during post-learning sleep. Intensifying neocortical slow oscillations (the hallmark of slow wave sleep by electrical or auditory stimulation and modulating specific neurotransmitters such as noradrenaline and glutamate likewise facilitates memory processing during sleep. With this evidence in mind, this article concludes by discussing different methodological caveats and ethical issues that should be considered when thinking about using sleep for cognitive enhancement in everyday applications.

  20. Metabolic consequences of sleep and sleep loss

    OpenAIRE

    Van Cauter, Eve; Spiegel, Karine; Tasali, Esra; Leproult, Rachel

    2008-01-01

    Reduced sleep duration and quality appear to be endemic in modern society. Curtailment of the bedtime period to minimum tolerability is thought to be efficient and harmless by many. It has been known for several decades that sleep is a major modulator of hormonal release, glucose regulation and cardiovascular function. In particular, slow wave sleep (SWS), thought to be the most restorative sleep stage, is associated with decreased heart rate, blood pressure, sympathetic nervous activity and ...

  1. Sleep apnea and sleep : diagnostic aspects

    OpenAIRE

    Sahlin, Carin

    2009-01-01

    Background: Patients with sleep apnea have frequent apneas and hypopneas during sleep. Apneas can be either central or obstructive. The apnea-hypopnea index (AHI) is the mean number of apneas and hypopneas per hour of sleep. Aims: 1) To evaluate the effect of a mandibular advancement device on obstructive apneas and sleep; 2) to evaluate the influence of body position on central apnea frequency; 3) to investigate whether obstructive or central apnea is related to mortality in patients with st...

  2. Alcohol disrupts sleep homeostasis.

    Science.gov (United States)

    Thakkar, Mahesh M; Sharma, Rishi; Sahota, Pradeep

    2015-06-01

    Alcohol is a potent somnogen and one of the most commonly used "over the counter" sleep aids. In healthy non-alcoholics, acute alcohol decreases sleep latency, consolidates and increases the quality (delta power) and quantity of NREM sleep during the first half of the night. However, sleep is disrupted during the second half. Alcoholics, both during drinking periods and during abstinences, suffer from a multitude of sleep disruptions manifested by profound insomnia, excessive daytime sleepiness, and altered sleep architecture. Furthermore, subjective and objective indicators of sleep disturbances are predictors of relapse. Finally, within the USA, it is estimated that societal costs of alcohol-related sleep disorders exceeds $18 billion. Thus, although alcohol-associated sleep problems have significant economic and clinical consequences, very little is known about how and where alcohol acts to affect sleep. In this review, we have described our attempts to unravel the mechanism of alcohol-induced sleep disruptions. We have conducted a series of experiments using two different species, rats and mice, as animal models. We performed microdialysis, immunohistochemical, pharmacological, sleep deprivation and lesion studies which suggest that the sleep-promoting effects of alcohol may be mediated via alcohol's action on the mediators of sleep homeostasis: adenosine (AD) and the wake-promoting cholinergic neurons of the basal forebrain (BF). Alcohol, via its action on AD uptake, increases extracellular AD resulting in the inhibition of BF wake-promoting neurons. Since binge alcohol consumption is a highly prevalent pattern of alcohol consumption and disrupts sleep, we examined the effects of binge drinking on sleep-wakefulness. Our results suggest that disrupted sleep homeostasis may be the primary cause of sleep disruption observed following binge drinking. Finally, we have also shown that sleep disruptions observed during acute withdrawal, are caused due to impaired

  3. 75 FR 81625 - Government-Owned Inventions; Availability for Licensing

    Science.gov (United States)

    2010-12-28

    ..., caused by Trypanosoma cruzi (T. cruzi), affects millions of people in Mexico and South and Central... and Rhodesian) of the parasites Trypanosoma brucei rhodesiensi and Trypanosoma cruzi, respectively... type is caused by the parasite Trypanosoma brucei gambiense, and the other is caused by the parasite...

  4. Use of Restriction Fragment Length Polymorphism of 18S rRNA ...

    African Journals Online (AJOL)

    The restriction fragment length polymorphism (RFLP) pattern of PCR products obtained was the same for T. brucei subspecies: T.b. brucei and T.b. gambiense but different for other trypanosome species and L. donovani. RFLP analysis was also done with genomic DNA from different trypanosome species, subspecies and ...

  5. Influence of sleeping pads on thermal comfort of sleeping bag

    OpenAIRE

    Vinš, Jiří

    2013-01-01

    Name of thesis: Influence of sleeping pads on thermal comfort of sleeping bag Abstract: The goals: The objective is to test different types of sleeping pads using the same sleeping bag in the specific stable conditions. Find and state test results for every sleeping pads. Conclusion of the thesis contain desicion, which sleeping pad is the best for thermal comfort in sleeping bag. Methods: Testing was conducted at 5 different sleeping pads using the same sleeping bag for each of the pads. Fou...

  6. Adolescents' Sleep Behaviors and Perceptions of Sleep

    Science.gov (United States)

    Noland, Heather; Price, James H.; Dake, Joseph; Telljohann, Susan K.

    2009-01-01

    Background: Sleep duration affects the health of children and adolescents. Shorter sleep durations have been associated with poorer academic performance, unintentional injuries, and obesity in adolescents. This study extends our understanding of how adolescents perceive and deal with their sleep issues. Methods: General education classes were…

  7. Sleep Disorders: Sleep-Related Breathing Disorders.

    Science.gov (United States)

    Burman, Deepa

    2017-09-01

    Sleep-related breathing disorders or sleep-disordered breathing are characterized by abnormal respiration during sleep. They are grouped into obstructive sleep apnea (OSA), central sleep apnea, sleep-related hypoventilation, and sleep-related hypoxemia disorder. OSA is a common disorder encountered in the family medicine setting that is increasingly being recognized because of the obesity epidemic and greater public and physician awareness. OSA is characterized by recurrent episodes of partial or complete closure of the upper airway resulting in disturbed breathing during sleep. It is associated with decreased quality of life and significant medical comorbidities. Untreated OSA can lead to a host of cardiovascular diseases including coronary artery disease, stroke, and atrial fibrillation. Patients who report symptoms of snoring, witnessed apneas, or daytime sleepiness should be screened for sleep apnea. In-laboratory attended diagnostic polysomnography or portable home sleep testing can be used to diagnose sleep apnea. Continuous positive airway pressure (CPAP) therapy is the first-line treatment for OSA in adults. Other modalities include mandibular advancement devices, surgery, or upper airway stimulation therapy. Adjunctive therapy should include weight loss in overweight patients, avoidance of sedatives and alcohol before sleep, and possibly positional therapy. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  8. 3D Architecture of the Trypanosoma brucei Flagella Connector, a Mobile Transmembrane Junction.

    Directory of Open Access Journals (Sweden)

    Johanna L Höög

    2016-01-01

    Full Text Available Cellular junctions are crucial for the formation of multicellular organisms, where they anchor cells to each other and/or supportive tissue and enable cell-to-cell communication. Some unicellular organisms, such as the parasitic protist Trypanosoma brucei, also have complex cellular junctions. The flagella connector (FC is a three-layered transmembrane junction that moves with the growing tip of a new flagellum and attaches it to the side of the old flagellum. The FC moves via an unknown molecular mechanism, independent of new flagellum growth. Here we describe the detailed 3D architecture of the FC suggesting explanations for how it functions and its mechanism of motility.We have used a combination of electron tomography and cryo-electron tomography to reveal the 3D architecture of the FC. Cryo-electron tomography revealed layers of repetitive filamentous electron densities between the two flagella in the interstitial zone. Though the FC does not change in length and width during the growth of the new flagellum, the interstitial zone thickness decreases as the FC matures. This investigation also shows interactions between the FC layers and the axonemes of the new and old flagellum, sufficiently strong to displace the axoneme in the old flagellum. We describe a novel filament, the flagella connector fibre, found between the FC and the axoneme in the old flagellum.The FC is similar to other cellular junctions in that filamentous proteins bridge the extracellular space and are anchored to underlying cytoskeletal structures; however, it is built between different portions of the same cell and is unique because of its intrinsic motility. The detailed description of its structure will be an important tool to use in attributing structure / function relationships as its molecular components are discovered in the future. The FC is involved in the inheritance of cell shape, which is important for the life cycle of this human parasite.

  9. Glucose uptake occurs by facilitated diffusion in procyclic forms of Trypanosoma brucei.

    Science.gov (United States)

    Wille, U; Seyfang, A; Duszenko, M

    1996-02-15

    The glucose transporter of Trypanosoma brucei procyclic forms was characterized and compared with its bloodstream form counterpart. Measuring the glucose consumption enzymatically, we determined a saturable uptake process of relatively high affinity (Km = 80 microM, Vmax = 4 nmol min-1 10(-8) cells), which showed substrate inhibition at glucose concentrations above 1.5 mM (Ki = 21 mM). Control experiments measuring deoxy-D-[3H]Glc uptake under zero-trans conditions indicated that substrate inhibition occurred on the level of glycolysis. Temperature-dependent kinetics revealed a temperature quotient of Q10 = 2.33 and an activation energy of Ea = 64 kJ mol-1. As shown by trans-stimulation experiments, glucose uptake was stereospecific for the D isomer, whereas L-glucose was not recognized. Inhibitor studies using either the uncoupler carbonylcyanide-4-(trifluoromethoxy)phenylhydrazone (5 microM), the H+/ATPase inhibitor N,N'-dicyclohexylcarbodiimide (20 microM), the ionophor monensin (1 microM), or the Na+/K+-ATPase inhibitor ouabain (1 mM) showed insignificant effects on transport efficiency. The procyclic glucose transporter was subsequently enriched in a plasma-membrane fraction and functionally reconstituted into proteoliposomes. Using Na+-free conditions in the absence of a proton gradient, the specific activity of D-[14C]glucose transport was determined as 2.9 nmol min-1 (mg protein)-1 at 0.2 mM glucose. From these cumulative results, we conclude that glucose uptake by the procyclic insect form of the parasite occurs by facilitated diffusion, similar to the hexose-transport system expressed in bloodstream forms. However, the markedly higher substrate affinity indicates a differential expression of different transporter isoforms throughout the lifecycle.

  10. Regulation of Trypanosoma brucei Total and Polysomal mRNA during Development within Its Mammalian Host.

    Directory of Open Access Journals (Sweden)

    Paul Capewell

    Full Text Available The gene expression of Trypanosoma brucei has been examined extensively in the blood of mammalian hosts and in forms found in the midgut of its arthropod vector, the tsetse fly. However, trypanosomes also undergo development within the mammalian bloodstream as they progress from morphologically 'slender forms' to transmissible 'stumpy forms' through morphological intermediates. This transition is temporally progressive within the first wave of parasitaemia such that gene expression can be monitored in relatively pure slender and stumpy populations as well as during the progression between these extremes. The development also represents the progression of cells from translationally active forms adapted for proliferation in the host to translationally quiescent forms, adapted for transmission. We have used metabolic labelling to quantitate translational activity in slender forms, stumpy forms and in forms undergoing early differentiation to procyclic forms in vitro. Thereafter we have examined the cohort of total mRNAs that are enriched throughout development in the mammalian bloodstream (slender, intermediate and stumpy forms, irrespective of strain, revealing those that exhibit consistent developmental regulation rather than sample specific changes. Transcripts that cosediment with polysomes in stumpy forms and slender forms have also been enriched to identify transcripts that escape translational repression prior to transmission. Combined, the expression and polysomal association of transcripts as trypanosomes undergo development in the mammalian bloodstream have been defined, providing a resource for trypanosome researchers. This facilitates the identification of those that undergo developmental regulation in the bloodstream and therefore those likely to have a role in the survival and capacity for transmission of stumpy forms.

  11. 3D Architecture of the Trypanosoma brucei Flagella Connector, a Mobile Transmembrane Junction

    Science.gov (United States)

    Höög, Johanna L.; Lacomble, Sylvain; Bouchet-Marquis, Cedric; Briggs, Laura; Park, Kristin; Hoenger, Andreas; Gull, Keith

    2016-01-01

    Background Cellular junctions are crucial for the formation of multicellular organisms, where they anchor cells to each other and/or supportive tissue and enable cell-to-cell communication. Some unicellular organisms, such as the parasitic protist Trypanosoma brucei, also have complex cellular junctions. The flagella connector (FC) is a three-layered transmembrane junction that moves with the growing tip of a new flagellum and attaches it to the side of the old flagellum. The FC moves via an unknown molecular mechanism, independent of new flagellum growth. Here we describe the detailed 3D architecture of the FC suggesting explanations for how it functions and its mechanism of motility. Methodology/Principal Findings We have used a combination of electron tomography and cryo-electron tomography to reveal the 3D architecture of the FC. Cryo-electron tomography revealed layers of repetitive filamentous electron densities between the two flagella in the interstitial zone. Though the FC does not change in length and width during the growth of the new flagellum, the interstitial zone thickness decreases as the FC matures. This investigation also shows interactions between the FC layers and the axonemes of the new and old flagellum, sufficiently strong to displace the axoneme in the old flagellum. We describe a novel filament, the flagella connector fibre, found between the FC and the axoneme in the old flagellum. Conclusions/Significance The FC is similar to other cellular junctions in that filamentous proteins bridge the extracellular space and are anchored to underlying cytoskeletal structures; however, it is built between different portions of the same cell and is unique because of its intrinsic motility. The detailed description of its structure will be an important tool to use in attributing structure / function relationships as its molecular components are discovered in the future. The FC is involved in the inheritance of cell shape, which is important for the life

  12. Virulence and pathogenicity of three Trypanosoma brucei rhodesiense stabilates in a Swiss white mouse model

    Directory of Open Access Journals (Sweden)

    Christopher Kariuki

    2015-05-01

    Full Text Available Background: A key objective in basic research on human African trypanosomiasis (HAT is developing a cheap and reliable experimental model of the disease for use in pathogenesis and drug studies.Objective: With a view to improving current models, a study was undertaken to characterise the virulence and pathogenicity of three Trypanosoma brucei rhodesiense stabilates, labelled as International Livestock Research Institute (ILRI-2918, ILRI-3953, and Institute of Primate Research (IPR-001, infected into Swiss white mice.Methods: Swiss white mice were infected intraperitoneally with trypanosomes and observedfor parasitaemia using wet blood smears obtained by tail snipping. Induction of late-stagedisease was undertaken using diminazene aceturate (40 mg/kg, Berenil with curativetreatment done using melarsoprol (3.6 mg/kg, Arsobal.Results: The prepatent period for the stabilates ranged from three to four days with mean peak parasitaemia ranging from Log10 6.40 to 8.36. First peak parasitaemia for all stabilates varied between six and seven days post infection (DPI followed by secondary latency in ILRI-2918 (15–17 DPI and IPR-001 (17–19 DPI. Survival times ranged from six DPI (ILRI-3953 to 86 DPI (IPR-001. Hindleg paresis was observed in both ILRI-3953 (at peak parasitaemia and ILRI-2918 (after relapse parasitaemia. Mice infected with IPR-001 survived until 54 DPI when curative treatment was undertaken.Conclusions: This study demonstrated that the stabilates ILRI-2918 and ILRI-3953 were unsuitable for modelling late-stage HAT in mice. The stabilate IPR-001 demonstrated the potential to induce chronic trypanosomiasis in Swiss white mice for use in development of a late-stage model of HAT.

  13. Sleep and Infant Learning

    Science.gov (United States)

    Tarullo, Amanda R.; Balsam, Peter D.; Fifer, William P.

    2011-01-01

    Human neonates spend the majority of their time sleeping. Despite the limited waking hours available for environmental exploration, the first few months of life are a time of rapid learning about the environment. The organization of neonate sleep differs qualitatively from adult sleep, and the unique characteristics of neonatal sleep may promote…

  14. The Sleeping Cerebellum

    NARCIS (Netherlands)

    Canto, Cathrin B; Onuki, Yoshiyuki; Bruinsma, Bastiaan; van der Werf, Ysbrand D; De Zeeuw, Chris I

    2017-01-01

    We sleep almost one-third of our lives and sleep plays an important role in critical brain functions like memory formation and consolidation. The role of sleep in cerebellar processing, however, constitutes an enigma in the field of neuroscience; we know little about cerebellar sleep-physiology,

  15. [Sleep habits among adolescents].

    Science.gov (United States)

    Sørensen, E; Ursin, R

    2001-01-30

    Norwegian adolescents report very high-perceived morning sleepiness. Delayed sleep phase may be biologically linked to puberty; adolescents sleep less, but may need more sleep than prepubertal children. The study was designed to investigate sleep habits, circadian rhythm and subjective satisfaction with sleep. Twenty-two high school students, age 17, and parents of 16 primary school pupils, age seven, answered a questionnaire on estimated sleep need, actual time in bed, sleep latency and adequacy of sleep. The average length of nocturnal sleep in the adolescents was 7.3 hrs on weekdays and 10.1 hrs on weekends. They went later to bed and rose earlier than the children, sleeping 1.7 hrs less before schooldays and 1.6 hrs more during the weekend than the 8.5 hrs which were their own sleep estimate. All the children were reported to satisfy their need for sleep, but none of the adolescents reported feeling content. The larger the difference between hours in bed on weekdays and hours in bed on weekends, the more dissatisfaction was observed. The present data suggest that the adolescents were chronic partially sleep deprived and had a tendency toward delayed sleep phase. They did not satisfy their need for sleep as defined by themselves, due to late bedtime throughout the week. Also, the late bedtime and late rise time on weekends maintained or furthered the delayed sleep phase.

  16. Sleep disorders in pregnancy.

    Science.gov (United States)

    Oyiengo, Dennis; Louis, Mariam; Hott, Beth; Bourjeily, Ghada

    2014-09-01

    Sleep disturbances are common in pregnancy and may be influenced by a multitude of factors. Pregnancy physiology may predispose to sleep disruption but may also result in worsening of some underlying sleep disorders, and the de novo development of others. Apart from sleep disordered breathing, the impact of sleep disorders on pregnancy, fetal, and neonatal outcomes is poorly understood. In this article, we review the literature and discuss available data pertaining to the most common sleep disorders in perinatal women. These include restless legs syndrome, insomnia, circadian pattern disturbances, narcolepsy, and sleep-disordered breathing. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. [Sleep in neurodegenerative disorders].

    Science.gov (United States)

    Happe, S; Mayer, G

    2006-10-01

    Neurodegenerative disorders are a group of heterogeneous, progressive disorders of varying etiology that affect one or more systems. They occur predominantly at older age, during which the structure and amount of sleep undergo changes. Neurodegenerative processes cause structural changes of the sleep/wake generators in the brainstem which result in disorders such as daytime sleepiness, insomnia, sleep-related movement and breathing disturbances, and disorders of the circadian rhythms. Some sleep disorders manifest years before the onset of neurodegenerative disorders and may serve as predictors. Polysomnography shows sleep fragmentation, tonic or phasic movements of the extremities, alteration of respiratory muscles, reduced slow wave sleep, REM sleep absence or without muscle atonia, increased arousal or wake activity, epileptiform EEG activity, and changes in sleep-related breathing. Very frequently, REM sleep behaviour disorder is associated with neurodegenerative disorders. In this overview we present symptoms, pathophysiology, and polysomnographic findings of sleep disorders in prevalent neurodegenerative disorders.

  18. Sleep and neurodegenerative diseases.

    Science.gov (United States)

    Chokroverty, Sudhansu

    2009-09-01

    Sleep disturbances are common in neurodegenerative diseases. Disturbed sleep can result in fatigue, irritability, morning headaches, impaired motor and cognitive skills, depression, and daytime somnolence. The major sleep complaints include insomnia, hypersomnia, parasomnia, excessive nocturnal motor activity, circadian sleep-wake rhythm disturbance, and respiratory dysrhythmia. The pathogenetic mechanisms of sleep disturbances may be secondary to direct structural alteration of the sleep-wake generating neurons or from several other indirect mechanisms. At the biochemical level, neurodegenerative diseases may be largely classified as tauopathies, alpha-synucleinopathies, and other diseases. Overnight polysomnography (PSG), Multiple Sleep Latency Test, Maintenance of Wakefulness Test, and actigraphy are some important diagnostic laboratory tests in the evaluation of sleep disturbances. Management of sleep disturbances is complex and is based primarily on the nature of the sleep disturbance. The clinical profiles, pathogenetic mechanisms, PSG findings, and management issues are discussed here with reference to some common neurodegenerative diseases. Thieme Medical Publishers.

  19. Sleep and Alzheimer's disease.

    Science.gov (United States)

    Peter-Derex, Laure; Yammine, Pierre; Bastuji, Hélène; Croisile, Bernard

    2015-02-01

    Sleep disorders are frequent in Alzheimer's disease (AD), with a significant impact on patients and caregivers and a major risk factor for early institutionalization. Micro-architectural sleep alterations, nocturnal sleep fragmentation, decrease in nocturnal sleep duration, diurnal napping and even inversion of the sleep-wake cycle are the main disorders observed in patients with AD. Experimental and epidemiological evidence for a close reciprocal interaction between cognitive decline and sleep alterations is growing. Management of sleep disorders in AD is pre-eminently behavioral. Association of melatonin and bright light treatment seems to be promising as well. The presence of sleep complaints, especially excessive somnolence in demented patients, should draw attention to possible associated sleep pathologies such as sleep apnea syndrome or restless legs syndrome. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Sleep and cognition.

    Science.gov (United States)

    Deak, Maryann C; Stickgold, Robert

    2010-07-01

    Sleep is a complex physiologic state, the importance of which has long been recognized. Lack of sleep is detrimental to humans and animals. Over the past decade, an important link between sleep and cognitive processing has been established. Sleep plays an important role in consolidation of different types of memory and contributes to insightful, inferential thinking. While the mechanism by which memories are processed in sleep remains unknown, several experimental models have been proposed. This article explores the link between sleep and cognition by reviewing (1) the effects of sleep deprivation on cognition, (2) the influence of sleep on consolidation of declarative and non-declarative memory, and (3) some proposed models of how sleep facilitates memory consolidation in sleep. Copyright © 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. Copyright © 2010 John Wiley & Sons, Ltd.

  1. Isolated sleep paralysis elicited by sleep interruption.

    Science.gov (United States)

    Takeuchi, T; Miyasita, A; Sasaki, Y; Inugami, M; Fukuda, K

    1992-06-01

    We elicited isolated sleep paralysis (ISP) from normal subjects by a nocturnal sleep interruption schedule. On four experimental nights, 16 subjects had their sleep interrupted for 60 minutes by forced awakening at the time when 40 minutes of nonrapid eye movement (NREM) sleep had elapsed from the termination of rapid eye movement (REM) sleep in the first or third sleep cycle. This schedule produced a sleep onset REM period (SOREMP) after the interruption at a high rate of 71.9%. We succeeded in eliciting six episodes of ISP in the sleep interruptions performed (9.4%). All episodes of ISP except one occurred from SOREMP, indicating a close correlation between ISP and SOREMP. We recorded verbal reports about ISP experiences and recorded the polysomnogram (PSG) during ISP. All of the subjects with ISP experienced inability to move and were simultaneously aware of lying in the laboratory. All but one reported auditory/visual hallucinations and unpleasant emotions. PSG recordings during ISP were characterized by a REM/W stage dissociated state, i.e. abundant alpha electroencephalographs and persistence of muscle atonia shown by the tonic electromyogram. Judging from the PSG recordings, ISP differs from other dissociated states such as lucid dreaming, nocturnal panic attacks and REM sleep behavior disorders. We compare some of the sleep variables between ISP and non-ISP nights. We also discuss the similarities and differences between ISP and sleep paralysis in narcolepsy.

  2. Sleep, Sleep Disturbance and Fertility in Women

    Science.gov (United States)

    Kloss, Jacqueline D.; Perlis, Michael; Zamzow, Jessica; Culnan, Elizabeth; Gracia, Clarisa

    2014-01-01

    Summary Sleep and sleep disturbances are increasingly recognized as determinants of women’s health and well-being, particularly in the context of the menstrual cycle, pregnancy, and menopause. At present, however, little is known about whether fertility is affected by sleep quantity and quality. That is, to what degree, and by what mechanisms, do sleep and/or its disturbances affect fertility? The purpose of this review is to synthesize what is known about sleep disturbances in relation to reproductive capacity. A model is provided, whereby stress, sleep dysregulation, and circadian misalignment are delineated for their potential relevance to infertility. Ultimately, if it is the case that sleep disturbance is associated with infertility, new avenues for clinical intervention may be possible. PMID:25458772

  3. Obesity and Sleep

    OpenAIRE

    WINDA LIVIYA NG

    2017-01-01

    This thesis examines the relationship between obesity and sleep problems, and the consequences of sleep problems on morbidity and mortality. Through a series of different methodologies and datasets, this thesis has found strong, consistent evidence supporting the role of obesity in causing sleep problems, and the benefit of weight loss in improving sleep problems. This thesis has also found evidence towards substantial life expectancy loss associated with having sleep problems. The findings f...

  4. Sleep: A Health Imperative

    OpenAIRE

    Luyster, Faith S.; Strollo, Patrick J.; Zee, Phyllis C.; Walsh, James K.

    2012-01-01

    Chronic sleep deficiency, defined as a state of inadequate or mistimed sleep, is a growing and underappreciated determinant of health status. Sleep deprivation contributes to a number of molecular, immune, and neural changes that play a role in disease development, independent of primary sleep disorders. These changes in biological processes in response to chronic sleep deficiency may serve as etiological factors for the development and exacerbation of cardiovascular and metabolic diseases an...

  5. Sleep disorders in children

    OpenAIRE

    Montgomery, Paul; Dunne, Danielle

    2007-01-01

    Sleep disorders may affect 20-30% of young children, and include excessive daytime sleepiness, problems getting to sleep (dysomnias), or undesirable phenomena during sleep (parasomnias), such as sleep terrors, and sleepwalking. Children with physical or learning disabilities are at increased risk of sleep disorders. Other risk factors include the child being the first born, having a difficult temperament or having had colic, and increased maternal responsiveness.

  6. Sleep disorders in children

    OpenAIRE

    Bruni, Oliveiero; Novelli, Luana

    2010-01-01

    Sleep disorders may affect between 20% and 30% of young children, and include problems getting to sleep (dyssomnias) or undesirable phenomena during sleep (parasomnias), such as sleep terrors and sleepwalking. Children with physical or learning disabilities are at increased risk of sleep disorders. Other risk factors include the child being the first born, having a difficult temperament or having had colic, and increased maternal responsiveness.

  7. Childhood epilepsy and sleep

    OpenAIRE

    Mohammed A Al-Biltagi

    2014-01-01

    Sleep and epilepsy are two well recognized conditions that interact with each other in a complex bi-directional way. Some types of epilepsies have increased activity during sleep disturbing it; while sleep deprivation aggravates epilepsy due to decreased seizure threshold. Epilepsy can deteriorate the sleep-related disorders and at the same time; the parasomnias can worsen the epilepsy. The secretion of sleep-related hormones can also be affected by the occurrence of seizures and supplementat...

  8. [Sleep: regulation and phenomenology].

    Science.gov (United States)

    Vecchierini, M-F

    2013-12-01

    This article describes the two-process model of sleep regulation. The 24-hour sleep-wake cycle is regulated by a homeostatic process and an endogenous, 2 oscillators, circadian process, under the influence of external synchronisers. These two processes are partially independent but influence each other, as shown in the two-sleep-process auto-regulation model. A reciprocal inhibition model of two interconnected neuronal groups, "SP on" and "SP off", explains the regular recurrence of paradoxical sleep. Sleep studies have primarily depended on observation of the subject and have determined the optimal conditions for sleep (position, external conditions, sleep duration and need) and have studied the consequences of sleep deprivation or modifications of sleep schedules. Then, electrophysiological recordings permitted the classification of sleep stages according to the observed EEG patterns. The course of a night's sleep is reported on a "hypnogram". The adult subject falls asleep in non-REM sleep (N1), then sleep deepens progressively to stages N2 and N3 with the appearance of spindles and slow waves (N2). Slow waves become more numerous in stage N3. Every 90minutes REM sleep recurs, with muscle atonia and rapid eye movements. These adult sleep patterns develop progressively during the 2 first years of life as total sleep duration decreases, with the reduction of diurnal sleep and of REM sleep. Around 2 to 4 months, spindles and K complexes appear on the EEG, with the differentiation of light and deep sleep with, however, a predominance of slow wave sleep. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  9. Sleep and Student Achievement

    OpenAIRE

    Eric R. Eide; Mark H. Showalter

    2012-01-01

    We explore the relationship between sleep and student performance on standardized tests. We model test scores as a nonlinear function of sleep, which allows us to compute the hours of sleep associated with maximum test scores. We refer to this as “optimal” hours of sleep. We also evaluate how the sleep and student performance relationship changes with age. We use the Panel Study of Income Dynamics-Child Development Supplement, which includes excellent control variables that are not usually av...

  10. Interaction between Gallotannin and a Recombinant Form of Arginine Kinase of Trypanosoma brucei: Thermodynamic and Spectrofluorimetric Evaluation

    Directory of Open Access Journals (Sweden)

    O. S. Adeyemi

    2014-01-01

    Full Text Available Current chemotherapies against trypanosomiasis are beset with diverse challenges, a situation which underscores the numerous research efforts aimed at finding newer and effective treatments. Arginine kinase of trypanosome has been validated as target for drug development against trypanosomiasis. The present study investigated the interaction between a recombinant form of the arginine kinase (rTbAK of trypanosome and gallotannin. The interaction between gallotannin and recombinant arginine kinase of Trypanosoma brucei caused significant decrease of enzyme activity. Kinetic analysis revealed the interaction to be of noncompetitive inhibition. Further thermodynamic analysis showed that the interaction between gallotannin and the recombinant arginine kinase was nonspontaneous and involved hydrophobic forces. The Ksv values and the FRET analysis suggest that static quenching of fluorescence intensity by gallotannin was static. Data revealed inhibitory interactions between gallotannin and rTbAK of trypanosome. Although the mechanism of inhibition is not clear yet, molecular docking studies are ongoing to clearly define the inhibitory interactions between the gallotannin and rTbAK. The knowledge of such binding properties would enrich development of selective inhibitors for the arginine kinase of Trypanosoma brucei.

  11. In Silico Identification and in Vitro Activity of Novel Natural Inhibitors of Trypanosoma brucei Glyceraldehyde-3-phosphate-dehydrogenase

    Directory of Open Access Journals (Sweden)

    Fabian C. Herrmann

    2015-09-01

    Full Text Available As part of our ongoing efforts to identify natural products with activity against pathogens causing neglected tropical diseases, we are currently performing an extensive screening of natural product (NP databases against a multitude of protozoan parasite proteins. Within this project, we screened a database of NPs from a commercial supplier, AnalytiCon Discovery (Potsdam, Germany, against Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH, a glycolytic enzyme whose inhibition deprives the parasite of energy supply. NPs acting as potential inhibitors of the mentioned enzyme were identified using a pharmacophore-based virtual screening and subsequent docking of the identified hits into the active site of interest. In a set of 700 structures chosen for the screening, 13 (1.9% were predicted to possess significant affinity towards the enzyme and were therefore tested in an in vitro enzyme assay using recombinant TbGAPDH. Nine of these in silico hits (69% showed significant inhibitory activity at 50 µM, of which two geranylated benzophenone derivatives proved to be particularly active with IC50 values below 10 µM. These compounds also showed moderate in vitro activity against T. brucei rhodesiense and may thus represent interesting starting points for further optimization.

  12. Proximity Interactions among Basal Body Components in Trypanosoma brucei Identify Novel Regulators of Basal Body Biogenesis and Inheritance

    Directory of Open Access Journals (Sweden)

    Hung Quang Dang

    2017-01-01

    Full Text Available The basal body shares similar architecture with centrioles in animals and is involved in nucleating flagellar axonemal microtubules in flagellated eukaryotes. The early-branching Trypanosoma brucei possesses a motile flagellum nucleated from the basal body that consists of a mature basal body and an adjacent pro-basal body. Little is known about the basal body proteome and its roles in basal body biogenesis and flagellar axoneme assembly in T. brucei. Here, we report the identification of 14 conserved centriole/basal body protein homologs and 25 trypanosome-specific basal body proteins. These proteins localize to distinct subdomains of the basal body, and several of them form a ring-like structure surrounding the basal body barrel. Functional characterization of representative basal body proteins revealed distinct roles in basal body duplication/separation and flagellar axoneme assembly. Overall, this work identified novel proteins required for basal body duplication and separation and uncovered new functions of conserved basal body proteins in basal body duplication and separation, highlighting an unusual mechanism of basal body biogenesis and inheritance in this early divergent eukaryote.

  13. Analysis of cosmid clones of nuclear DNA from Trypanosome brucei shows that the genes for variant surface glycoproteins are clustered in the genome.

    NARCIS (Netherlands)

    D. Valerio (Dinko); T. de Lange; P. Borst (Piet); F.G. Grosveld (Frank); L.H.T. van der Ploeg

    1982-01-01

    textabstractTrypanosoma brucei contains more than a hundred genes coding for the different variant surface glycoproteins (VSGs). Activation of some of these genes involves the duplication of the gene (the basic copy or BC) and transposition of the duplicate to an expression site (yielding the

  14. The mitochondrial FAD-dependent glycerol-3-phosphate dehydrogenase of Trypanosomatidae and the glycocomal redox balance of insect stages of Trypanosoma brucei and Leishmania spp.

    NARCIS (Netherlands)

    Guerra, D.G.; Decottignies, A.; Bakker, B.M.; Michels, P.A.M.

    2006-01-01

    The genes for the mitochondrial FAD-dependent glycerol-3-phosphate dehydrogenase were identified in Trypanosoma brucei and Leishmania major genomes. We have expressed the L. major gene in Saccharomyces cerevisiae and confirmed the subcellular localization and activity of the produced enzyme. Using

  15. Trypanosoma brucei TBRGG1, a mitochondrial oligo(U)-binding protein that co-localizes with an in vitro RNA editing activity

    NARCIS (Netherlands)

    Vanhamme, L.; Perez-Morga, D.; Marchal, C.; Speijer, D.; Lambert, L.; Geuskens, M.; Alexandre, S.; Ismaïli, N.; Göringer, U.; Benne, R.; Pays, E.

    1998-01-01

    We report the characterization of a Trypanosoma brucei 75-kDa protein of the RGG (Arg-Gly-Gly) type, termed TBRGG1. Dicistronic and monocistronic transcripts of the TBRGG1 gene were produced by both alternative splicing and polyadenylation. TBRGG1 was found in two or three forms that differ in their

  16. Discovery of novel Trypanosoma brucei phosphodiesterase B1 inhibitors by virtual screening against the unliganded TbrPDEB1 crystal structure

    NARCIS (Netherlands)

    Jansen, C.; Wang, H.; Kooistra, A.J.; de Graaf, C.; Orrling, K.M.; Tenor, H.; Seebeck, T.; de Esch, I.J.P.; Ke, H.; Leurs, R.

    2013-01-01

    Trypanosoma brucei cyclic nucleotide phosphodiesterase B1 (TbrPDEB1) and TbrPDEB2 have recently been validated as new therapeutic targets for human African trypanosomiasis by both genetic and pharmacological means. In this study we report the crystal structure of the catalytic domain of the

  17. Immunospecific immunoglobulins and IL-10 as markers for Trypanosoma brucei rhodesiense late stage disease in experimentally infected vervet monkeys

    DEFF Research Database (Denmark)

    Ngotho, Maina; Kagira, J.M.; Jensen, Henrik Michael Elvang

    2009-01-01

    OBJECTIVE: To determine the usefulness of IL-10 and immunoglobulin M (IgM) as biomarkers for staging HAT in vervet monkeys, a useful pathogenesis model for humans. METHODS: Vervet monkeys were infected with Trypanosoma brucei rhodesiense and subsequently given sub-curative and curative treatment 28...

  18. Metabolic consequences of sleep and sleep loss.

    Science.gov (United States)

    Van Cauter, Eve; Spiegel, Karine; Tasali, Esra; Leproult, Rachel

    2008-09-01

    Reduced sleep duration and quality appear to be endemic in modern society. Curtailment of the bedtime period to minimum tolerability is thought to be efficient and harmless by many. It has been known for several decades that sleep is a major modulator of hormonal release, glucose regulation and cardiovascular function. In particular, slow wave sleep (SWS), thought to be the most restorative sleep stage, is associated with decreased heart rate, blood pressure, sympathetic nervous activity and cerebral glucose utilization, compared with wakefulness. During SWS, the anabolic growth hormone is released while the stress hormone cortisol is inhibited. In recent years, laboratory and epidemiologic evidence have converged to indicate that sleep loss may be a novel risk factor for obesity and type 2 diabetes. The increased risk of obesity is possibly linked to the effect of sleep loss on hormones that play a major role in the central control of appetite and energy expenditure, such as leptin and ghrelin. Reduced leptin and increased ghrelin levels correlate with increases in subjective hunger when individuals are sleep restricted rather than well rested. Given the evidence, sleep curtailment appears to be an important, yet modifiable, risk factor for the metabolic syndrome, diabetes and obesity. The marked decrease in average sleep duration in the last 50 years coinciding with the increased prevalence of obesity, together with the observed adverse effects of recurrent partial sleep deprivation on metabolism and hormonal processes, may have important implications for public health.

  19. Central Sleep Apnea - Mayo Clinic

    Science.gov (United States)

    ... sleep apnea while using continuous positive airway pressure (CPAP) for their sleep apnea treatment. This condition is ... may increase the risk of central sleep apnea. CPAP. Some people with obstructive sleep apnea develop central ...

  20. The Sleeping Cerebellum.

    Science.gov (United States)

    Canto, Cathrin B; Onuki, Yoshiyuki; Bruinsma, Bastiaan; van der Werf, Ysbrand D; De Zeeuw, Chris I

    2017-05-01

    We sleep almost one-third of our lives and sleep plays an important role in critical brain functions like memory formation and consolidation. The role of sleep in cerebellar processing, however, constitutes an enigma in the field of neuroscience; we know little about cerebellar sleep-physiology, cerebro-cerebellar interactions during sleep, or the contributions of sleep to cerebellum-dependent memory consolidation. Likewise, we do not understand why cerebellar malfunction can lead to changes in the sleep-wake cycle and sleep disorders. In this review, we evaluate how sleep and cerebellar processing may influence one another and highlight which scientific routes and technical approaches could be taken to uncover the mechanisms underlying these interactions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. [Neurological sleep disorders].

    Science.gov (United States)

    Khatami, Ramin

    2014-11-01

    Neurological sleep disorders are common in the general population and may have a strong impact on quality of life. General practitioners play a key role in recognizing and managing sleep disorders in the general population. They should therefore be familiar with the most important neurological sleep disorders. This review provides a comprehensive overview of the most prevalent and important neurological sleep disorders, including Restless legs syndrome (with and without periodic limb movements in sleep), narcolepsy, NREM- and REM-sleep parasomnias and the complex relationship between sleep and epilepsies. Although narcolepsy is considered as a rare disease, recent discoveries in narcolepsy research provided insight in the function of brain circuitries involved in sleep wake regulation. REM sleep behavioral parasomnia (RBD) is increasingly recognized to represent an early manifestation of neurodegenerative disorders, in particular evolving synucleinopathies. Early diagnosis may thus open new perspectives for developing novel treatment options by targeting neuroprotective substances.

  2. Sleep in Neurodegenerative Diseases.

    Science.gov (United States)

    Iranzo, Alex

    2016-03-01

    Disorders of sleep are an integral part of neurodegenerative diseases and include insomnia, sleep-wake cycle disruption, excessive daytime sleepiness that may be manifested as persistent somnolence or sudden onset of sleep episodes, obstructive and central sleep apnea, rapid eye movement sleep behavior disorder, and restless legs syndrome. The origin of these sleep disorders is multifactorial including degeneration of the brain areas that modulate sleep, the symptoms of the disease, and the effect of medications. Treatment of sleep disorders in patients with neurodegenerative diseases should be individualized and includes behavioral therapy, sleep hygiene, bright light therapy, melatonin, hypnotics, waking-promoting agents, and continuous positive airway pressure. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Sleep: a health imperative.

    Science.gov (United States)

    Luyster, Faith S; Strollo, Patrick J; Zee, Phyllis C; Walsh, James K

    2012-06-01

    Chronic sleep deficiency, defined as a state of inadequate or mistimed sleep, is a growing and underappreciated determinant of health status. Sleep deprivation contributes to a number of molecular, immune, and neural changes that play a role in disease development, independent of primary sleep disorders. These changes in biological processes in response to chronic sleep deficiency may serve as etiological factors for the development and exacerbation of cardiovascular and metabolic diseases and, ultimately, a shortened lifespan. Sleep deprivation also results in significant impairments in cognitive and motor performance which increase the risk of motor vehicle crashes and work-related injuries and fatal accidents. The American Academy of Sleep Medicine and the Sleep Research Society have developed this statement to communicate to national health stakeholders the current knowledge which ties sufficient sleep and circadian alignment in adults to health.

  4. Trypanosoma brucei: analysis of cytoplasmic Ca2+ during differentiation of bloodstream stages in vitro.

    Science.gov (United States)

    Stojdl, D F; Clarke, M W

    1996-06-01

    The highly regulated intracellular concentration of calcium (Ca2+) is a well-described regulator of diverse cellular events, including cell cycle control. In the present study we have addressed the regulation of cytosolic Ca2+ in differentiation events in the life cycle of the protozoan parasite Trypanosoma brucei. Bloodstream form (BSF) trypanosomes include the mitotically active long slender forms (LS) which differentiate to two nondividing stages--intermediate (INT) which transform into short stumpy (SS) forms. An axenic in vitro culture system was used to cultivate LS to a density greater than 1.0 x 10(6) cells/ml/day. Populations of the intermediate BSF (INT) and SS were derived from cultured LS by treatment with difluoromethyl ornithine (DFMO, 100 microM) for 2 and 4 days, respectively. A semiquantitative reverse transcriptase-coupled polymerase chain reaction protocol (SQ-RT-PCR) was developed to objectively distinguish the three BSF by monitoring the relative levels of stage-specific mRNAs--cytochrome oxidase II (COXII), variant surface glycoprotein, and procyclin during the differentiation of LS to SS, showing an increase in COXII and procyclin mRNA expression during this process of differentiation. Basal cytosolic Ca2+ levels [Ca2+]i of populations of LS, INT, and SS were studied using Indo-1 dual emission fluorometry. [Ca2+]i was maximal in dividing LS cells and was shown to decrease coincidentally with early events in the process of differentiation to INT and SS. Thapsigargin (1 microM), reported to cause the release of Ca2+ from the endoplasmic reticulum, elevated [Ca2+]i by about 30-60 nM in all BSF; however, the total thapsigargin-releasable stores decreased in parallel with the decrease in basal [Ca2+]i. Control treatments verified that elevations in [Ca2+]i in response to thapsigargin were intracellular in origin. These results may reflect the cessation of cytosolic Ca2+ transients involved in the regulation of mitosis as the parasite exits from

  5. The use of yellow fluorescent hybrids to indicate mating in Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Ferris Vanessa

    2008-02-01

    Full Text Available Abstract Background Trypanosoma brucei undergoes genetic exchange in its insect vector, the tsetse fly, by an unknown mechanism. The difficulties of working with this experimental system of genetic exchange have hampered investigation, particularly because the trypanosome life cycle stages involved cannot be cultured in vitro and therefore must be examined in the insect. Searching for small numbers of hybrid trypanosomes directly in the fly has become possible through the incorporation of fluorescent reporter genes, and we have previously carried out a successful cross using a reporter-repressor strategy. However, we could not be certain that all fluorescent trypanosomes observed in that cross were hybrids, due to mutations of the repressor leading to spontaneous fluorescence, and we have therefore developed an alternative strategy. Results To visualize the production of hybrids in the fly, parental trypanosome clones were transfected with a gene encoding Green Fluorescent Protein (GFP or Red Fluorescent Protein (RFP. Co-infection of flies with red and green fluorescent parental trypanosomes produced yellow fluorescent hybrids, which were easily visualized in the fly salivary glands. Yellow trypanosomes were not seen in midgut or proventricular samples and first appeared in the glands as epimastigotes as early as 13 days after fly infection. Cloned progeny originating from individual salivary glands had yellow, red, green or no fluorescence and were confirmed as hybrids by microsatellite, molecular karyotype and kinetoplast (mitochondrial DNA analyses. Hybrid clones showed biparental inheritance of both nuclear and kinetoplast genomes. While segregation and reassortment of the reporter genes and microsatellite alleles were consistent with Mendelian inheritance, flow cytometry measurement of DNA content revealed both diploid and polyploid trypanosomes among the hybrid progeny clones. Conclusion The strategy of using production of yellow hybrids

  6. Nifurtimox plus Eflornithine for late-stage sleeping sickness in Uganda: a case series.

    Science.gov (United States)

    Checchi, Francesco; Piola, Patrice; Ayikoru, Harriet; Thomas, Florence; Legros, Dominique; Priotto, Gerardo

    2007-11-07

    We report efficacy and safety outcomes from a prospective case series of 31 late-stage T.b. gambiense sleeping sickness (Human African Trypanosomiasis, HAT) patients treated with a combination of nifurtimox and eflornithine (N+E) in Yumbe, northwest Uganda in 2002-2003, following on a previously reported terminated trial in nearby Omugo, in which 17 patients received the combination under the same conditions. Eligible sequential late-stage patients received 400 mg/Kg/day eflornithine (Ornidyl, Sanofi-Aventis) for seven days plus 15 mg/Kg/day (20 mg for children nifurtimox (Lampit, Bayer AG) for ten days. Efficacy (primary outcome) was monitored for 24 months post discharge. Clinical and laboratory adverse events (secondary outcome) were monitored during treatment. All 31 patients were discharged alive, but two died post-discharge of non-HAT and non-treatment causes, and one was lost to follow-up. Efficacy ranged from 90.3% to 100.0% according to analysis approach. Five patients experienced major adverse events during treatment, and neutropenia was common (9/31 patients). Combined with the previous group of 17 trial patients, this case series yields a group of 48 patients treated with N+E, among whom no deaths judged to be treatment- or HAT-related, no treatment terminations and no relapses have been noted, a very favourable outcome in the context of late-stage disease. N+E could be the most promising combination regimen available for sleeping sickness, and deserves further evaluation.

  7. Nifurtimox plus Eflornithine for late-stage sleeping sickness in Uganda: a case series.

    Directory of Open Access Journals (Sweden)

    Francesco Checchi

    2007-11-01

    Full Text Available We report efficacy and safety outcomes from a prospective case series of 31 late-stage T.b. gambiense sleeping sickness (Human African Trypanosomiasis, HAT patients treated with a combination of nifurtimox and eflornithine (N+E in Yumbe, northwest Uganda in 2002-2003, following on a previously reported terminated trial in nearby Omugo, in which 17 patients received the combination under the same conditions.Eligible sequential late-stage patients received 400 mg/Kg/day eflornithine (Ornidyl, Sanofi-Aventis for seven days plus 15 mg/Kg/day (20 mg for children <15 years old nifurtimox (Lampit, Bayer AG for ten days. Efficacy (primary outcome was monitored for 24 months post discharge. Clinical and laboratory adverse events (secondary outcome were monitored during treatment. All 31 patients were discharged alive, but two died post-discharge of non-HAT and non-treatment causes, and one was lost to follow-up. Efficacy ranged from 90.3% to 100.0% according to analysis approach. Five patients experienced major adverse events during treatment, and neutropenia was common (9/31 patients.Combined with the previous group of 17 trial patients, this case series yields a group of 48 patients treated with N+E, among whom no deaths judged to be treatment- or HAT-related, no treatment terminations and no relapses have been noted, a very favourable outcome in the context of late-stage disease. N+E could be the most promising combination regimen available for sleeping sickness, and deserves further evaluation.

  8. Alcohol disrupts sleep homeostasis

    Science.gov (United States)

    Thakkar, Mahesh M.; Sharma, Rishi; Sahota, Pradeep

    2014-01-01

    Alcohol is a potent somnogen and one of the most commonly used “over the counter” sleep aids. In healthy non-alcoholics, acute alcohol decreases sleep latency, consolidates and increases the quality (delta power) and quantity of NREM sleep during the first half of the night. However, sleep is disrupted during the second half. Alcoholics, both during drinking periods and during abstinences, suffer from a multitude of sleep disruptions manifested by profound insomnia, excessive daytime sleepiness, and altered sleep architecture. Furthermore, subjective and objective indicators of sleep disturbances are predictors of relapse. Finally, within the USA, it is estimated that societal costs of alcohol-related sleep disorders exceeds $18 billion. Thus, although alcohol-associated sleep problems have significant economic and clinical consequences, very little is known about how and where alcohol acts to affect sleep. In this review, we have described our attempts to understand how and where alcohol acts to affect sleep. We have conducted a series of experiments using two different species, rats and mice, as animal models, and a combination of multi-disciplinary experimental methodologies to examine and understand anatomical and cellular substrates mediating the effects of acute and chronic alcohol exposure on sleep-wakefulness. The results of our studies suggest that the sleep-promoting effects of alcohol may be mediated via alcohol’s action on the mediators of sleep homeostasis: adenosine (AD) and the wake-promoting cholinergic neurons of the basal forebrain (BF). Alcohol, via its action on AD uptake, increases extracellular AD resulting in the inhibition of BF wake-promoting neurons. Lesions of the BF cholinergic neurons or blockade of AD A1 receptors results in attenuation of alcohol-induced sleep promotion, suggesting that AD and BF cholinergic neurons are critical for sleep-promoting effects of alcohol. Since binge alcohol consumption is a highly prevalent pattern

  9. [Insomnia and sleep apnea].

    Science.gov (United States)

    Bayon, V; Léger, D

    2014-02-01

    The presence of insomnia in patients with sleep apnea seems paradoxical as excessive sleepiness is one of the major symptoms of sleep apnea. However, recent research has shown that about half of patients with sleep disorder breathing experience insomnia. Moreover, patients complaining of insomnia or non-restorative sleep may also present with moderate to severe sleep apnea syndromes. Thus, in recent years, clinicians have become more aware of the possible association between insomnia and sleep apnea. This article reviews data published on different aspects of this co-occurrence. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  10. [Sleep and pregnancy].

    Science.gov (United States)

    Rutskova, E M; Pigareva, M L

    2011-01-01

    Sleep disturbances are frequent during pregnancy and are currently regarded as one of the most important factors determining pregnancy outcome. Detailed research of sleep features during pregnancy is obviously essential. In the present review recent data concerning changes in sleep structure and regulation in pregnant women and rats - main subjects of experimental sleep research, are given, including surmised mechanisms underlying such changes. The importance of women's sleep integrity preservation during pregnancy for the viability and normal development of the fetus is emphasized and possible ways of pathological influence of sleep disorders during this period are discussed.

  11. All about Sleep (For Parents)

    Science.gov (United States)

    ... November 2014 More on this topic for: Parents Kids Teens Naps Sleepwalking Nightmares Night Terrors Sleep and Your ... Month-Old Obstructive Sleep Apnea Sleep Problems in Teens Separation Anxiety ... I Need to Sleep? What Sleep Is and Why All Kids Need It How Much Sleep Do I Need? ...

  12. Sleep physiology and sleep disorders in childhood

    OpenAIRE

    El Shakankiry HM

    2011-01-01

    Hanan M El ShakankiryKing Fahd University Hospital, Al Dammam University, Al Khobar, Kingdom of Saudi ArabiaAbstract: Sleep has long been considered as a passive phenomenon, but it is now clear that it is a period of intense brain activity involving higher cortical functions. Overall, sleep affects every aspect of a child's development, particularly higher cognitive functions. Sleep concerns are ranked as the fifth leading concern of parents. Close to one third of all children suffer ...

  13. Identifying Adolescent Sleep Problems

    Science.gov (United States)

    Short, Michelle A.; Gradisar, Michael; Gill, Jason; Camfferman, Danny

    2013-01-01

    Objectives To examine the efficacy of self-report and parental report of adolescent sleep problems and compare these findings to the incidence of adolescents who fulfill clinical criteria for a sleep problem. Sleep and daytime functioning factors that predict adolescents’ self-identification of a sleep problem will also be examined. Method 308 adolescents (aged 13–17 years) from eight socioeconomically diverse South Australian high schools participated in this study. Participants completed a survey battery during class time, followed by a 7-day Sleep Diary and the Flinders Fatigue Scale completed on the final day of the study. Parents completed a Sleep, Medical, Education and Family History Survey. Results The percentage of adolescents fulfilling one or more of the criteria for a sleep problem was inordinately high at 66%. Adolescent self-reporting a sleep problem was significantly lower than the adolescents who had one or more of the clinical criteria for a sleep problem (23.1% vs. 66.6%; χ2 = 17.46, padolescent having a sleep problem was significantly lower than adolescent self-report (14.3% vs. 21.1%, pAdolescents who reported unrefreshing sleep were 4.81 times more likely to report a sleep problem. For every hour that bedtime was delayed, the odds of self-reporting a sleep problem increased by 1.91 times, while each additional 10 minutes taken to fall asleep increased the odds 1.40 times. Conclusion While many adolescents were found to have sleep patterns indicative of a sleep problem, only a third of this number self-identify having a sleep problem, while only a sixth of this number are indicated by parental report. This study highlights important features to target in future sleep education and intervention strategies for both adolescents and parents. PMID:24086501

  14. Excreted/Secreted Proteins from Trypanosome Procyclic Strains

    Directory of Open Access Journals (Sweden)

    Celestine Michelle Atyame Nten

    2010-01-01

    Full Text Available Trypanosoma secretome was shown to be involved in parasite virulence and is suspected of interfering in parasite life-cycle steps such as establishment in the Glossina midgut, metacyclogenesis. Therefore, we attempted to identify the proteins secreted by procyclic strains of T. brucei gambiense and T. brucei brucei, responsible for human and animal trypanosomiasis, respectively. Using mass spectrometry, 427 and 483 nonredundant proteins were characterized in T. brucei brucei and T. brucei gambiense secretomes, respectively; 35% and 42% of the corresponding secretome proteins were specifically secreted by T. brucei brucei and T. brucei gambiense, respectively, while 279 proteins were common to both subspecies. The proteins were assigned to 12 functional classes. Special attention was paid to the most abundant proteases (14 families because of their potential implication in the infection process and nutrient supply. The presence of proteins usually secreted via an exosome pathway suggests that this type of process is involved in trypanosome ESP secretion. The overall results provide leads for further research to develop novel tools for blocking trypanosome transmission.

  15. Sleep and Women

    Science.gov (United States)

    ... stories Pediatrics poor sleep pop culture Pregnancy PTSD race Railroad Safety relationships relaxation REM Sleep Behavior Disorder Restless legs syndrome School School Start Times Sexual Dysfunction Shift Work SIDS ...

  16. Teenagers and sleep

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000872.htm Teenagers and sleep To use the sharing features on this page, ... need. What Makes it Hard for Teens to Sleep? Several factors make it hard for teens to ...

  17. Sleep Issues and Sundowning

    Science.gov (United States)

    ... more: Treatments for Sleep Changes Back to top Coping strategies for sleep issues and sundowning If the ... in 1980, the Alzheimer's Association is the world's leading voluntary health organization in Alzheimer's care, support and ...

  18. Computing sleep deficiency.

    Science.gov (United States)

    Erren, Thomas C; Groß, J Valerie; Lewis, Philip

    2017-11-20

    Sleep deficiency is a major public health concern. Since epidemiological studies play an important role in public health evaluations, this theoretical paper pursues answers to the question: 'How can we compute sleep deficiency as informative measures of exposures or doses in observational research?' Starting from the social jetlag concept and based on the chronodisruption rationale, we illustrate and discuss five approaches (one established and four untested, each with unique strengths and limitations) to quantify sleep deficiency by focusing on the timing and duration of sleep. Hitherto, social jetlag and chronodisruption rationale were neither explicitly proposed nor developed as assessments of sleep deficiency but, as we suggest, could potentially be utilized to this end. This first foray into computing sleep deficiency in epidemiological studies makes clear that laboratory, field and epidemiological collaboration is pre-requisite to elucidating potential (co-)causal roles of sleep deficiency in disease endpoints. © 2017 European Sleep Research Society.

  19. Sleep in Neurodevelopmental Disorders

    Science.gov (United States)

    Esbensen, Anna J; Schwichtenberg, Amy J

    2017-01-01

    Individuals with intellectual and developmental disabilities (IDD) experience sleep problems at higher rates than the general population. Although individuals with IDD are a heterogeneous group, several sleep problems cluster within genetic syndromes or disorders. This review summarizes the prevalence of sleep problems experienced by individuals with Angelman syndrome, Cornelia de Lange syndrome, Cri du Chat syndrome, Down syndrome, fragile X syndrome, Prader-Willi syndrome, Smith-Magenis syndrome, Williams syndrome, autism spectrum disorder, and idiopathic IDD. Factors associated with sleep problems and the evidence for sleep treatments are reviewed for each neurodevelopmental disorder. Sleep research advancements in neurodevelopmental disorders are reviewed, including the need for consistency in defining and measuring sleep problems, considerations for research design and reporting of results, and considerations when evaluating sleep treatments. PMID:28503406

  20. Sleep and Eating Disorders.

    Science.gov (United States)

    Allison, Kelly C; Spaeth, Andrea; Hopkins, Christina M

    2016-10-01

    Insomnia is related to an increased risk of eating disorders, while eating disorders are related to more disrupted sleep. Insomnia is also linked to poorer treatment outcomes for eating disorders. However, over the last decade, studies examining sleep and eating disorders have relied on surveys, with no objective measures of sleep for anorexia nervosa or bulimia nervosa, and only actigraphy data for binge eating disorder. Sleep disturbance is better defined for night eating syndrome, where sleep efficiency is reduced and melatonin release is delayed. Studies that include objectively measured sleep and metabolic parameters combined with psychiatric comorbidity data would help identify under what circumstances eating disorders and sleep disturbance produce an additive effect for symptom severity and for whom poor sleep would increase risk for an eating disorder. Cognitive behavior therapy for insomnia may be a helpful addition to treatment of those with both eating disorder and insomnia.

  1. Sleep and moral awareness

    National Research Council Canada - National Science Library

    Barnes, Christopher M; Gunia, Brian C; Wagner, David T

    2015-01-01

    The implications of sleep for morality are only starting to be explored. Extending the ethics literature, we contend that because bringing morality to conscious attention requires effort, a lack of sleep leads to low moral awareness...

  2. Treatments for Sleep Changes

    Science.gov (United States)

    ... overall sleep quality for older adults. Use of sleep medications is associated with a greater chance of falls and other risks that may outweigh the benefits of treatment. Sign up for our weekly e- ...

  3. Sleep and Human Aging.

    Science.gov (United States)

    Mander, Bryce A; Winer, Joseph R; Walker, Matthew P

    2017-04-05

    Older adults do not sleep as well as younger adults. Why? What alterations in sleep quantity and quality occur as we age, and are there functional consequences? What are the underlying neural mechanisms that explain age-related sleep disruption? This review tackles these questions. First, we describe canonical changes in human sleep quantity and quality in cognitively normal older adults. Second, we explore the underlying neurobiological mechanisms that may account for these human sleep alterations. Third, we consider the functional consequences of age-related sleep disruption, focusing on memory impairment as an exemplar. We conclude with a discussion of a still-debated question: do older adults simply need less sleep, or rather, are they unable to generate the sleep that they still need? Copyright © 2017. Published by Elsevier Inc.

  4. Pediatric Sleep Surgery

    Directory of Open Access Journals (Sweden)

    Cecille Gail Sulman

    2014-06-01

    Full Text Available Adenotonsillectomy is the most common surgery performed for sleep disordered breathing with good outcomes. Children with obesity, craniofacial disorders, and neurologic impairment are at risk for persistent sleep apnea after adenotonsillectomy. Techniques exist to address obstructive lesions of the palate, tongue base, or craniofacial skeleton in children with persistent sleep apnea. Children with obstructive sleep apnea have a higher rate of peri-operative complications.

  5. Sleep and Metabolism: An Overview

    Directory of Open Access Journals (Sweden)

    Sunil Sharma

    2010-01-01

    Full Text Available Sleep and its disorders are increasingly becoming important in our sleep deprived society. Sleep is intricately connected to various hormonal and metabolic processes in the body and is important in maintaining metabolic homeostasis. Research shows that sleep deprivation and sleep disorders may have profound metabolic and cardiovascular implications. Sleep deprivation, sleep disordered breathing, and circadian misalignment are believed to cause metabolic dysregulation through myriad pathways involving sympathetic overstimulation, hormonal imbalance, and subclinical inflammation. This paper reviews sleep and metabolism, and how sleep deprivation and sleep disorders may be altering human metabolism.

  6. Programmed Cell Death in Procyclic Form Trypanosoma brucei rhodesiense - Identification of Differentially Expressed Genes during Con A Induced Death

    Directory of Open Access Journals (Sweden)

    Welburn Susan C

    1999-01-01

    Full Text Available Trypanosoma brucei rhodesiense can be induced to undergo apoptosis after stimulation with Con A. As cell death in these parasites is associated with de novo gene expression we have applied a differential display technique, Randomly Amplified Differential Expressed Sequence-Polymerase Chain Reaction (RADES-PCR to the study of gene expression during Con A induced cell death in these organisms. Twenty-two differentially displayed products have been cloned and sequenced. These represent the first endogenous genes to be identified as implicated in cellular death in trypanosomatids (the most primitive eukaryote in which apoptosis has been described. Evidence for an ancestral death machinery, `proto-apoptosis' in single celled organisms is discussed.

  7. High-confidence glycosome proteome for procyclic form Trypanosoma brucei by epitope-tag organelle enrichment and SILAC proteomics.

    Science.gov (United States)

    Güther, Maria Lucia S; Urbaniak, Michael D; Tavendale, Amy; Prescott, Alan; Ferguson, Michael A J

    2014-06-06

    The glycosome of the pathogenic African trypanosome Trypanosoma brucei is a specialized peroxisome that contains most of the enzymes of glycolysis and several other metabolic and catabolic pathways. The contents and transporters of this membrane-bounded organelle are of considerable interest as potential drug targets. Here we use epitope tagging, magnetic bead enrichment, and SILAC quantitative proteomics to determine a high-confidence glycosome proteome for the procyclic life cycle stage of the parasite using isotope ratios to discriminate glycosomal from mitochondrial and other contaminating proteins. The data confirm the presence of several previously demonstrated and suggested pathways in the organelle and identify previously unanticipated activities, such as protein phosphatases. The implications of the findings are discussed.

  8. Physiology of Sleep.

    Science.gov (United States)

    Carley, David W; Farabi, Sarah S

    2016-02-01

    IN BRIEF Far from a simple absence of wakefulness, sleep is an active, regulated, and metabolically distinct state, essential for health and well-being. In this article, the authors review the fundamental anatomy and physiology of sleep and its regulation, with an eye toward interactions between sleep and metabolism.

  9. The Functions of Sleep

    Directory of Open Access Journals (Sweden)

    Samson Z Assefa

    2015-08-01

    Full Text Available Sleep is a ubiquitous component of animal life including birds and mammals. The exact function of sleep has been one of the mysteries of biology. A considerable number of theories have been put forward to explain the reason(s for the necessity of sleep. To date, while a great deal is known about what happens when animals sleep, there is no definitive comprehensive explanation as to the reason that sleep is an inevitable part of animal functioning. It is well known that sleep is a homeostatically regulated body process, and that prolonged sleep deprivation is fatal in animals. In this paper, we present some of the theories as to the functions of sleep and provide a review of some hypotheses as to the overall physiologic function of sleep. To better understand the purpose for sleeping, we review the effects of sleep deprivation on physical, neurocognitive and psychic function. A better understanding of the purpose for sleeping will be a great advance in our understanding of the nature of the animal kingdom, including our own.

  10. Changing your sleep habits

    Science.gov (United States)

    ... sleep over a 24-hour period. Remember, the quality of sleep and how rested you feel afterward is as ... During the day: Be more active. Walk or exercise for at least 30 ... your sleep. Find ways to manage stress. Learn about relaxation ...

  11. Regulators of Trypanosoma brucei cell cycle progression and differentiation identified using a kinome-wide RNAi screen.

    Directory of Open Access Journals (Sweden)

    Nathaniel G Jones

    2014-01-01

    Full Text Available The African trypanosome, Trypanosoma brucei, maintains an integral link between cell cycle regulation and differentiation during its intricate life cycle. Whilst extensive changes in phosphorylation have been documented between the mammalian bloodstream form and the insect procyclic form, relatively little is known about the parasite's protein kinases (PKs involved in the control of cellular proliferation and differentiation. To address this, a T. brucei kinome-wide RNAi cell line library was generated, allowing independent inducible knockdown of each of the parasite's 190 predicted protein kinases. Screening of this library using a cell viability assay identified ≥42 PKs that are required for normal bloodstream form proliferation in culture. A secondary screen identified 24 PKs whose RNAi-mediated depletion resulted in a variety of cell cycle defects including in G1/S, kinetoplast replication/segregation, mitosis and cytokinesis, 15 of which are novel cell cycle regulators. A further screen identified for the first time two PKs, named repressor of differentiation kinase (RDK1 and RDK2, depletion of which promoted bloodstream to procyclic form differentiation. RDK1 is a membrane-associated STE11-like PK, whilst RDK2 is a NEK PK that is essential for parasite proliferation. RDK1 acts in conjunction with the PTP1/PIP39 phosphatase cascade to block uncontrolled bloodstream to procyclic form differentiation, whilst RDK2 is a PK whose depletion efficiently induces differentiation in the absence of known triggers. Thus, the RNAi kinome library provides a valuable asset for functional analysis of cell signalling pathways in African trypanosomes as well as drug target identification and validation.

  12. Crystal Structures of TbCatB and rhodesain, potential chemotherapeutic targets and major cysteine proteases of Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Iain D Kerr

    2010-06-01

    Full Text Available Trypanosoma brucei is the etiological agent of Human African Trypanosomiasis, an endemic parasitic disease of sub-Saharan Africa. TbCatB and rhodesain are the sole Clan CA papain-like cysteine proteases produced by the parasite during infection of the mammalian host and are implicated in the progression of disease. Of considerable interest is the exploration of these two enzymes as targets for cysteine protease inhibitors that are effective against T. brucei.We have determined, by X-ray crystallography, the first reported structure of TbCatB in complex with the cathepsin B selective inhibitor CA074. In addition we report the structure of rhodesain in complex with the vinyl-sulfone K11002.The mature domain of our TbCat*CA074 structure contains unique features for a cathepsin B-like enzyme including an elongated N-terminus extending 16 residues past the predicted maturation cleavage site. N-terminal Edman sequencing reveals an even longer extension than is observed amongst the ordered portions of the crystal structure. The TbCat*CA074 structure confirms that the occluding loop, which is an essential part of the substrate-binding site, creates a larger prime side pocket in the active site cleft than is found in mammalian cathepsin B-small molecule structures. Our data further highlight enhanced flexibility in the occluding loop main chain and structural deviations from mammalian cathepsin B enzymes that may affect activity and inhibitor design. Comparisons with the rhodesain*K11002 structure highlight key differences that may impact the design of cysteine protease inhibitors as anti-trypanosomal drugs.

  13. Characterization of Two Mitochondrial Flavin Adenine Dinucleotide-Dependent Glycerol-3-Phosphate Dehydrogenases in Trypanosoma brucei

    Czech Academy of Sciences Publication Activity Database

    Škodová, Ingrid; Verner, Zdeněk; Bringaud, F.; Fabian, P.; Lukeš, Julius; Horváth, A.

    2013-01-01

    Roč. 12, č. 12 (2013), s. 1664-1673 ISSN 1535-9778 R&D Projects: GA ČR(CZ) GAP305/11/2179; GA ČR GD206/09/H026; GA MŠk LH12104 Institutional support: RVO:60077344 Keywords : alternative NADH dehydrogenase * inducible expression system * blood-stream forms * complex-I * procyclic trypanosomes * sleeping sickness * oxidase * localization * metabolism * cycle Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.179, year: 2013

  14. Sleep and Metabolism: An Overview

    OpenAIRE

    Sunil Sharma; Mani Kavuru

    2010-01-01

    Sleep and its disorders are increasingly becoming important in our sleep deprived society. Sleep is intricately connected to various hormonal and metabolic processes in the body and is important in maintaining metabolic homeostasis. Research shows that sleep deprivation and sleep disorders may have profound metabolic and cardiovascular implications. Sleep deprivation, sleep disordered breathing, and circadian misalignment are believed to cause metabolic dysregulation through myriad pathways i...

  15. Exercise Effects on Sleep Physiology

    OpenAIRE

    Sunao eUchida; Kohei eShioda; Yuko eMorita; Chie eKubota; Masashi eGaneko; Noriko eTakeda; Noriko eTakeda

    2012-01-01

    This mini-review focuses on the effects of exercise on sleep. In its early days, sleep research largely focused on central nervous system (CNS) physiology using standardized tabulations of several sleep-specific landmark electroencephalogram (EEG) waveforms. Though coarse, this method has enabled the observation and inspection of numerous uninterrupted sleep phenomena. Thus, research on the effects of exercise on sleep began, in the 1960’s, with a focus primarily on sleep EEG (CNS sleep) c...

  16. Sleep, Health, and Society.

    Science.gov (United States)

    Grandner, Michael A

    2017-03-01

    Biological needs for sleep are met by engaging in behaviors that are largely influenced by the environment, social norms and demands, and societal influences and pressures. Insufficient sleep duration and sleep disorders such as insomnia and sleep apnea are highly prevalent in the US population. This article outlines some of these downstream factors, including cardiovascular and metabolic disease risk, neurocognitive dysfunction, and mortality, as well as societal factors such as age, sex, race/ethnicity, and socioeconomics. This review also discusses societal factors related to sleep, such as globalization, health disparities, public policy, public safety, and changing patterns of use of technology. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. The detection and treatment of human African trypanosomiasis

    Directory of Open Access Journals (Sweden)

    Bouteille B

    2012-06-01

    Full Text Available Bernard Bouteille,1 Alain Buguet21Laboratory of Parasitology, Dupuytren University Hospital of Limoges, France; 2Polyclinic Marie-Louise Poto-Djembo, Pointe-Noire, CongoAbstract: Human African trypanosomiasis (HAT is caused by the injection of Trypanosoma brucei (T. b. gambiense or T. b. rhodesiense by Glossina, the tsetse fly. Three historical eras followed the exclusive clinical approach of the 19th century. At the turn of the century, the “initial research” era was initiated because of the dramatic spread of HAT throughout intertropical Africa, and scientists discovered the agent and its vector. Two entities, recurrent fever and sleeping sickness, were then considered a continuum between hemolymphatic stage 1 and meningoencephalitic stage 2. Treatments were developed. Soon after World War I, specific services and mobile teams were created, initiating the “epidemiological” era, during which populations were visited, screened, and treated. As a result, by 1960, annual new cases were rare. New mass screening and staging tools were then developed in a third, “modern” era, especially to counter a new epidemic wave. Currently, diagnosis still relies on microscopic detection of trypanosomes without (wet and thick blood films or with concentration techniques (capillary tube centrifugation, miniature anion-exchange centrifugation technique. Staging is a vital step.Stage 1 patients are treated on site with pentamidine or suramin. However, stage 2 patients are treated in specialized facilities, using drugs that are highly toxic and/or that require complex administration procedures (melarsoprol, eflornithine, or nifurtimox-eflornithine combination therapy. Suramin and melarsoprol are the only medications active against Rhodesian HAT. Staging still relies on cerebrospinal fluid examination for trypanosome detection and white blood cell counts: stage 1, absence of trypanosomes, white blood cell counts ≤ 5/µL; stage 2, presence of

  18. Sleep and Athletic Performance.

    Science.gov (United States)

    Watson, Andrew M

    Sleep is an essential component of health and well-being, with significant impacts on physical development, emotional regulation, cognitive performance, and quality of life. Along with being an integral part of the recovery and adaptive process between bouts of exercise, accumulating evidence suggests that increased sleep duration and improved sleep quality in athletes are associated with improved performance and competitive success. In addition, better sleep may reduce the risk of both injury and illness in athletes, not only optimizing health but also potentially enhancing performance through increased participation in training. Despite this, most studies have found that athletes fail to obtain the recommended amount of sleep, threatening both performance and health. Athletes face a number of obstacles that can reduce the likelihood of obtaining proper sleep, such as training and competition schedules, travel, stress, academic demands, and overtraining. In addition, athletes have been found to demonstrate poor self-assessment of their sleep duration and quality. In light of this, athletes may require more careful monitoring and intervention to identify individuals at risk and promote proper sleep to improve both performance and overall health. This review attempts to highlight the recent literature regarding sleep issues in athletes, the effects of sleep on athletic performance, and interventions to enhance proper sleep in athletes.

  19. Circadian rhythm sleep disorders

    Directory of Open Access Journals (Sweden)

    Morgenthaler TI

    2012-05-01

    Full Text Available Bhanu P Kolla,1,2 R Robert Auger,1,2 Timothy I Morgenthaler11Mayo Center for Sleep Medicine, 2Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN, USAAbstract: Misalignment between endogenous circadian rhythms and the light/dark cycle can result in pathological disturbances in the form of erratic sleep timing (irregular sleep–wake rhythm, complete dissociation from the light/dark cycle (circadian rhythm sleep disorder, free-running type, delayed sleep timing (delayed sleep phase disorder, or advanced sleep timing (advanced sleep phase disorder. Whereas these four conditions are thought to involve predominantly intrinsic mechanisms, circadian dysrhythmias can also be induced by exogenous challenges, such as those imposed by extreme work schedules or rapid transmeridian travel, which overwhelm the ability of the master clock to entrain with commensurate rapidity, and in turn impair approximation to a desired sleep schedule, as evidenced by the shift work and jet lag sleep disorders. This review will focus on etiological underpinnings, clinical assessments, and evidence-based treatment options for circadian rhythm sleep disorders. Topics are subcategorized when applicable, and if sufficient data exist. The length of text associated with each disorder reflects the abundance of associated literature, complexity of management, overlap of methods for assessment and treatment, and the expected prevalence of each condition within general medical practice.Keywords: circadian rhythm sleep disorders, assessment, treatment

  20. [Sleep duration and metabolism].

    Science.gov (United States)

    Viot-Blanc, V

    2015-12-01

    Sleep duration has gradually diminished during the last decade while obesity and type 2 diabetes have become epidemics. Experimental sleep curtailment leads to increased appetite, hormonal disturbances and, especially, insulin resistance. Numerous epidemiological studies have therefore examined whether habitual short sleep is associated with obesity and type 2 diabetes. A large majority of cross-sectional studies have confirmed an association between short, and also long sleep duration and obesity in adults more than in the elderly. Short sleep is strongly associated to obesity in children and adolescents. Prospective studies, including studies in children, are not conclusive with regard to the effect of short sleep on the incidence of obesity. Both short and long sleep durations are associated with diabetes, but only short sleep duration seems predictive of future diabetes. Insomnia seems to be a strong contributor to short sleep duration but the association of insomnia with obesity is not clear. Insomnia is associated with type 2 diabetes and also predictive of a higher incidence. Other studies have shown that short sleep duration and insomnia are associated with, and sometime predictive of, other components of the metabolic syndrome, especially hypertension and the risk of coronary disease. The treatment of short sleep duration and insomnia with regard to their effects on the metabolic syndrome merits further study. Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  1. Family Disorganization, Sleep Hygiene, and Adolescent Sleep Disturbance

    Science.gov (United States)

    Billows, Michael; Gradisar, Michael; Dohnt, Hayley; Johnston, Anna; McCappin, Stephanie; Hudson, Jennifer

    2009-01-01

    The link between sleep hygiene and adolescent sleep is well documented, though evidence suggests contributions from other factors, particularly the family environment. The present study examined whether sleep hygiene mediated the relationship between family disorganization and self-reported sleep onset latency, total sleep time, and daytime…

  2. Sleep and Sleep Problems: From Birth to 3

    Science.gov (United States)

    Du Mond, Courtney; Mindell, Jodi A.

    2011-01-01

    Sleep is an important aspect of a child's early development and is essential to family well-being. During their first 3 years, infants and toddlers spend more than 50% of their lives sleeping. However, concerns about sleep and sleep problems are among the most common issues brought to the attention of pediatricians. Although sleep is one of the…

  3. Sleep apnoea and stroke.

    Science.gov (United States)

    Sharma, Sameer; Culebras, Antonio

    2016-12-01

    Sleep disorders have been known to physicians for a long time. In his famous aphorisms, Hippocrates said "Sleep or watchfulness exceeding that which is customary, augurs unfavorably". Modern medicine has been able to disentangle some of the phenomena that disturb sleep. Among the most notable offenders is sleep apnoea that has gained prominence in the past few decades. It is being proposed as one of the potentially modifiable risk factors for vascular diseases including stroke. The pathological mechanisms linking sleep apnoea to vascular risk factors include hypoxia, cardiac arrhythmias, dysautonomia, impaired glucose tolerance, hypertension, dyslipidaemia and inflammation. In this article, we review literature linking sleep apnoea and stroke, including sleep apnoea as a risk factor for primary prevention with the potential to improve outcome after acute stroke and as a secondary risk factor, amenable to modification and hence vascular risk reduction.

  4. Sleep and Salivary Cortisol

    DEFF Research Database (Denmark)

    Garde, Anne Helene; Karlson, Bernt; Hansen, Åse Marie

    2011-01-01

    The aim of the present chapter was to analyze whether measures of cortisol in saliva were associated with measures of sleep and to explore if divergent results were related to underlying differences in theoretic assumptions and methods. Measures of sleep quality included sleep duration, overall...... sleep quality, difficulty falling asleep, disturbed sleep, and sleep deprivation. Twenty-three papers were found to fulfill the inclusion criteria. Cortisol measures were grouped into single time points at different times during the day, deviations at different time periods during the day, reactivity...... and recovery after a standardized laboratory test, area under the curve and response to dexamethasone test. A large proportion of the studies included showed non-significant findings, which, in several cases, may be a result of low power. The most consistent results were a positive association between sleep...

  5. Dreaming without REM sleep.

    Science.gov (United States)

    Oudiette, Delphine; Dealberto, Marie-José; Uguccioni, Ginevra; Golmard, Jean-Louis; Merino-Andreu, Milagros; Tafti, Mehdi; Garma, Lucile; Schwartz, Sophie; Arnulf, Isabelle

    2012-09-01

    To test whether mental activities collected from non-REM sleep are influenced by REM sleep, we suppressed REM sleep using clomipramine 50mg (an antidepressant) or placebo in the evening, in a double blind cross-over design, in 11 healthy young men. Subjects were awakened every hour and asked about their mental activity. The marked (81%, range 39-98%) REM-sleep suppression induced by clomipramine did not substantially affect any aspects of dream recall (report length, complexity, bizarreness, pleasantness and self-perception of dream or thought-like mentation). Since long, complex and bizarre dreams persist even after suppressing REM sleep either partially or totally, it suggests that the generation of mental activity during sleep is independent of sleep stage. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. PSYCHIATRIC DISORDERS AND SLEEP

    Science.gov (United States)

    Krystal, Andrew D.

    2012-01-01

    SYNOPSIS Psychiatric disorders and sleep are related in important ways. In contrast to the longstanding view of this relationship which viewed sleep problems as symptoms of psychiatric disorders, there is growing experimental evidence that the relationship between psychiatric disorders and sleep is complex and includes bi-directional causation. In this article we provide the evidence that supports this point of view, reviewing the data on the sleep disturbances seen in patients with psychiatric disorders but also reviewing the data on the impact of sleep disturbances on psychiatric conditions. Although much has been learned about the psychiatric disorders-sleep relationship, additional research is needed to better understand these relationships. This work promises to improve our ability to understand both of these phenomena and to allow us to better treat the many patients with sleep disorders and with psychiatric disorders. PMID:23099143

  7. Local sleep and learning.

    Science.gov (United States)

    Huber, Reto; Ghilardi, M Felice; Massimini, Marcello; Tononi, Giulio

    2004-07-01

    Human sleep is a global state whose functions remain unclear. During much of sleep, cortical neurons undergo slow oscillations in membrane potential, which appear in electroencephalograms as slow wave activity (SWA) of sleep. It has been suggested that SWA homeostasis may reflect synaptic changes underlying a cellular need for sleep. If this were so, inducing local synaptic changes should induce local SWA changes, and these should benefit neural function. Here we show that sleep homeostasis indeed has a local component, which can be triggered by a learning task involving specific brain regions. Furthermore, we show that the local increase in SWA after learning correlates with improved performance of the task after sleep. Thus, sleep homeostasis can be induced on a local level and can benefit performance.

  8. Sleep patterns of co-sleeping and solitary sleeping infants and mothers: a longitudinal study.

    Science.gov (United States)

    Volkovich, Ella; Ben-Zion, Hamutal; Karny, Daphna; Meiri, Gal; Tikotzky, Liat

    2015-11-01

    Controversies exist regarding the impact of co-sleeping on infant sleep quality. In this context, the current study examined: (a) the differences in objective and subjective sleep patterns between co-sleeping (mostly room-sharing) and solitary sleeping mother-infant dyads; (b) the predictive links between maternal sleep during pregnancy and postnatal sleeping arrangement; (c) the bi-directional prospective associations between sleeping arrangement and infant/maternal sleep quality at three and six months postpartum. The sample included 153 families recruited during pregnancy. Data were obtained in home settings during the third trimester of pregnancy and at three and six months postpartum. Mothers were asked to monitor their own sleep and their infants' sleep for five nights using actigraphy and sleep diaries. Questionnaires were used to assess sleeping arrangements, feeding methods, socio-demographic characteristics, and maternal depressive and anxiety symptoms. Mothers of co-sleeping infants reported more infant night-wakings than mothers of solitary sleeping infants. However, none of the objective sleep measures was significantly different between co-sleeping and solitary sleeping infants, after controlling for feeding techniques. Co-sleeping mothers had significantly more objective and subjective sleep disturbances than mothers in the solitary sleeping group. Moreover, poorer maternal sleep during pregnancy and at three months postpartum predicted higher levels of co-sleeping at six months. Mothers of co-sleeping infants report more infant night-wakings, and experience poorer sleep than mothers of solitary sleeping infants. The quality of maternal sleep should be taken into clinical consideration when parents consult about co-sleeping. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. The acidocalcisome vacuolar transporter chaperone 4 catalyzes the synthesis of polyphosphate in insect-stages of Trypanosoma brucei and T. cruzi.

    Science.gov (United States)

    Ulrich, Paul N; Lander, Noelia; Kurup, Samarchith P; Reiss, Laura; Brewer, Jessica; Soares Medeiros, Lia C; Miranda, Kildare; Docampo, Roberto

    2014-01-01

    Polyphosphate is a polymer of inorganic phosphate found in both prokaryotes and eukaryotes. Polyphosphate typically accumulates in acidic, calcium-rich organelles known as acidocalcisomes, and recent research demonstrated that vacuolar transporter chaperone 4 catalyzes its synthesis in yeast. The human pathogens Trypanosoma brucei and T. cruzi possess vacuolar transporter chaperone 4 homologs. We demonstrate that T. cruzi vacuolar transporter chaperone 4 localizes to acidocalcisomes of epimastigotes by immunofluorescence and immuno-electron microscopy and that the recombinant catalytic region of the T. cruzi enzyme is a polyphosphate kinase. RNA interference of the T. brucei enzyme in procyclic form parasites reduced short chain polyphosphate levels and resulted in accumulation of pyrophosphate. These results suggest that this trypanosome enzyme is an important component of a polyphosphate synthase complex that utilizes ATP to synthesize and translocate polyphosphate to acidocalcisomes in insect stages of these parasites. © 2013 The Author(s) Journal of Eukaryotic Microbiology © 2013 International Society of Protistologists.

  10. Trypanosoma brucei aquaglyceroporin 2 is a high-affinity transporter for pentamidine and melaminophenyl arsenic drugs and the main genetic determinant of resistance to these drugs

    Science.gov (United States)

    Munday, Jane C.; Eze, Anthonius A.; Baker, Nicola; Glover, Lucy; Clucas, Caroline; Aguinaga Andrés, David; Natto, Manal J.; Teka, Ibrahim A.; McDonald, Jennifer; Lee, Rebecca S.; Graf, Fabrice E.; Ludin, Philipp; Burchmore, Richard J. S.; Turner, C. Michael R.; Tait, Andy; MacLeod, Annette; Mäser, Pascal; Barrett, Michael P.; Horn, David; De Koning, Harry P.

    2014-01-01

    Objectives Trypanosoma brucei drug transporters include the TbAT1/P2 aminopurine transporter and the high-affinity pentamidine transporter (HAPT1), but the genetic identity of HAPT1 is unknown. We recently reported that loss of T. brucei aquaglyceroporin 2 (TbAQP2) caused melarsoprol/pentamidine cross-resistance (MPXR) in these parasites and the current study aims to delineate the mechanism by which this occurs. Methods The TbAQP2 loci of isogenic pairs of drug-susceptible and MPXR strains of T. brucei subspecies were sequenced. Drug susceptibility profiles of trypanosome strains were correlated with expression of mutated TbAQP2 alleles. Pentamidine transport was studied in T. brucei subspecies expressing TbAQP2 variants. Results All MPXR strains examined contained TbAQP2 deletions or rearrangements, regardless of whether the strains were originally adapted in vitro or in vivo to arsenicals or to pentamidine. The MPXR strains and AQP2 knockout strains had lost HAPT1 activity. Reintroduction of TbAQP2 in MPXR trypanosomes restored susceptibility to the drugs and reinstated HAPT1 activity, but did not change the activity of TbAT1/P2. Expression of TbAQP2 sensitized Leishmania mexicana promastigotes 40-fold to pentamidine and >1000-fold to melaminophenyl arsenicals and induced a high-affinity pentamidine transport activity indistinguishable from HAPT1 by Km and inhibitor profile. Grafting the TbAQP2 selectivity filter amino acid residues onto a chimeric allele of AQP2 and AQP3 partly restored susceptibility to pentamidine and an arsenical. Conclusions TbAQP2 mediates high-affinity uptake of pentamidine and melaminophenyl arsenicals in trypanosomes and TbAQP2 encodes the previously reported HAPT1 activity. This finding establishes TbAQP2 as an important drug transporter. PMID:24235095

  11. Trypanosoma brucei TbIF1 inhibits the essential Finf1/inf-ATPase in the infectious form of the parasite

    Czech Academy of Sciences Publication Activity Database

    Panicucci, Brian; Gahura, Ondřej; Zíková, Alena

    2017-01-01

    Roč. 11, č. 4 (2017), č. článku e0005552. ISSN 1935-2735 R&D Projects: GA MŠk(CZ) EE2.3.30.0032; GA ČR GA17-22248S Institutional support: RVO:60077344 Keywords : mt * TblF1 * Trypanosoma brucei Subject RIV: EE - Microbiology, Virology Impact factor: 3.834, year: 2016

  12. Genetic Dissociation of Daily Sleep and Sleep Following Thermogenetic Sleep Deprivation in Drosophila.

    Science.gov (United States)

    Dubowy, Christine; Moravcevic, Katarina; Yue, Zhifeng; Wan, Joy Y; Van Dongen, Hans P A; Sehgal, Amita

    2016-05-01

    Sleep rebound-the increase in sleep that follows sleep deprivation-is a hallmark of homeostatic sleep regulation that is conserved across the animal kingdom. However, both the mechanisms that underlie sleep rebound and its relationship to habitual daily sleep remain unclear. To address this, we developed an efficient thermogenetic method of inducing sleep deprivation in Drosophila that produces a substantial rebound, and applied the newly developed method to assess sleep rebound in a screen of 1,741 mutated lines. We used data generated by this screen to identify lines with reduced sleep rebound following thermogenetic sleep deprivation, and to probe the relationship between habitual sleep amount and sleep following thermogenetic sleep deprivation in Drosophila. To develop a thermogenetic method of sleep deprivation suitable for screening, we thermogenetically stimulated different populations of wake-promoting neurons labeled by Gal4 drivers. Sleep rebound following thermogenetically-induced wakefulness varies across the different sets of wake-promoting neurons that were stimulated, from very little to quite substantial. Thermogenetic activation of neurons marked by the c584-Gal4 driver produces both strong sleep loss and a substantial rebound that is more consistent within genotypes than rebound following mechanical or caffeine-induced sleep deprivation. We therefore used this driver to induce sleep deprivation in a screen of 1,741 mutagenized lines generated by the Drosophila Gene Disruption Project. Flies were subjected to 9 h of sleep deprivation during the dark period and released from sleep deprivation 3 h before lights-on. Recovery was measured over the 15 h following sleep deprivation. Following identification of lines with reduced sleep rebound, we characterized baseline sleep and sleep depth before and after sleep deprivation for these hits. We identified two lines that consistently exhibit a blunted increase in the duration and depth of sleep after

  13. Sleep from an islamic perspective

    Directory of Open Access Journals (Sweden)

    Ahmed S BaHammam

    2011-01-01

    Full Text Available Sleep medicine is a relatively new scientific specialty. Sleep is an important topic in Islamic literature, and the Quran and Hadith discuss types of sleep, the importance of sleep, and good sleep practices. Islam considers sleep as one of the signs of the greatness of Allβh (God and encourages followers to explore this important sign. The Quran describes different types of sleep, and these correspond with sleep stages identified by modern science. The Quran discusses the beneficial effects of sleep and emphasizes the importance of maintaining a pattern of light and darkness. A mid-day nap is an important practice for Muslims, and the Prophet Muhammad peace be upon him (pbuh promoted naps as beneficial. In accordance with the practice and instructions of Muhammad (pbuh, Muslims have certain sleep habits and these sleep habits correspond to some of the sleep hygiene rules identified by modern science. Details during sleep include sleep position, like encouraging sleep on the right side and discouraging sleep in the prone position. Dream interpretation is an established science in the Islamic literature and Islamic scholars have made significant contributions to theories of dream interpretation. We suggest that sleep scientists examine religious literature in general and Islamic literature in particular, to understand the views, behaviors, and practices of ancient people about the sleep and sleep disorders. Such studies may help to answer some unresolved questions in sleep science or lead to new areas of inquiry.

  14. Chronic sleep reduction in adolescents

    OpenAIRE

    Dewald-Kaufmann, J.F.

    2012-01-01

    Based on the results of this thesis, it can be concluded that sleep problems and chronic sleep reduction have a high impact on adolescents’ daytime functioning. Additionally, this research shows that gradual sleep extension can improve adolescents’ sleep and especially their chronic sleep reduction. This approach has beneficial effects on adolescents’ depressive symptoms and their cognitive performance.

  15. Chronic sleep reduction in adolescents

    NARCIS (Netherlands)

    Dewald-Kaufmann, J.F.

    2012-01-01

    Based on the results of this thesis, it can be concluded that sleep problems and chronic sleep reduction have a high impact on adolescents’ daytime functioning. Additionally, this research shows that gradual sleep extension can improve adolescents’ sleep and especially their chronic sleep reduction.

  16. Sleep from an Islamic perspective.

    Science.gov (United States)

    Bahammam, Ahmed S

    2011-10-01

    Sleep medicine is a relatively new scientific specialty. Sleep is an important topic in Islamic literature, and the Quran and Hadith discuss types of sleep, the importance of sleep, and good sleep practices. Islam considers sleep as one of the signs of the greatness of Allνh (God) and encourages followers to explore this important sign. The Quran describes different types of sleep, and these correspond with sleep stages identified by modern science. The Quran discusses the beneficial effects of sleep and emphasizes the importance of maintaining a pattern of light and darkness. A mid-day nap is an important practice for Muslims, and the Prophet Muhammad peace be upon him (pbuh) promoted naps as beneficial. In accordance with the practice and instructions of Muhammad (pbuh), Muslims have certain sleep habits and these sleep habits correspond to some of the sleep hygiene rules identified by modern science. Details during sleep include sleep position, like encouraging sleep on the right side and discouraging sleep in the prone position. Dream interpretation is an established science in the Islamic literature and Islamic scholars have made significant contributions to theories of dream interpretation. We suggest that sleep scientists examine religious literature in general and Islamic literature in particular, to understand the views, behaviors, and practices of ancient people about the sleep and sleep disorders. Such studies may help to answer some unresolved questions in sleep science or lead to new areas of inquiry.

  17. Identification and Functional Characterisation of CRK12:CYC9, a Novel Cyclin-Dependent Kinase (CDK-Cyclin Complex in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Séverine Monnerat

    Full Text Available The protozoan parasite, Trypanosoma brucei, is spread by the tsetse fly and causes trypanosomiasis in humans and animals. Both the life cycle and cell cycle of the parasite are complex. Trypanosomes have eleven cdc2-related kinases (CRKs and ten cyclins, an unusually large number for a single celled organism. To date, relatively little is known about the function of many of the CRKs and cyclins, and only CRK3 has previously been shown to be cyclin-dependent in vivo. Here we report the identification of a previously uncharacterised CRK:cyclin complex between CRK12 and the putative transcriptional cyclin, CYC9. CRK12:CYC9 interact to form an active protein kinase complex in procyclic and bloodstream T. brucei. Both CRK12 and CYC9 are essential for the proliferation of bloodstream trypanosomes in vitro, and we show that CRK12 is also essential for survival of T. brucei in a mouse model, providing genetic validation of CRK12:CYC9 as a novel drug target for trypanosomiasis. Further, functional characterisation of CRK12 and CYC9 using RNA interference reveals roles for these proteins in endocytosis and cytokinesis, respectively.

  18. Detection of Trypanosoma brucei in field-captured tsetse flies and identification of host species fed on by the infected flies.

    Science.gov (United States)

    Konnai, Satoru; Mekata, Hirohisa; Odbileg, Raadan; Simuunza, Martin; Chembensof, Mwelwa; Witola, William Harold; Tembo, Mwase Enala; Chitambo, Harrison; Inoue, Noboru; Onuma, Misao; Ohashi, Kazuhiko

    2008-08-01

    The prevalence of trypanosome infections in tsetse flies in the Chiawa area of Lower Zambezi in Zambia, with endemic trypanosomosis, was determined by a polymerase chain reaction (PCR) method that allowed the detection of trypanosome DNA and determination of the type of animal host fed on by the tsetse fly Glossina pallidipes, using tsetse-derived DNA extracts as templates. Ninety G. pallidipes (82 females and 8 males; 18.3%) of the 492 flies captured by baited biconical traps tested positive for the presence of Trypanosoma brucei species genomic DNA. Of the 90 T. brucei-positive flies, 47 (52.2%) also tested positive for vertebrate mitochondrial DNA. Sequence analysis of the vertebrate mitochondrial DNA amplicons established that they originated from 8 different vertebrate species, namely, human (Homo sapiens), African elephant (Loxodonta cyclotis), African buffalo (Syncerus caffer), waterbuck (Kobus ellipsiprymnus), roan antelope (Hippotragus equinus), greater kudu (Tragelaphus strepsiceros), warthog (Phacochoerus africanus), and goat (Capra hircus). Furthermore, to investigate the prevalence of trypanosome infections in domestic goats in the same area where trypanosomes had been detected in tsetse files, a total of 86 goats were randomly selected from 6 different herds. Among the selected goats, 36 (41.9%) were found to be positive for T. brucei species. This combined detection method would be an ideal approach not only for mass screening for infection prevalence in tsetse populations, but also for the prediction of natural reservoirs in areas endemic for trypanosomosis.

  19. Immunization with recombinant beta-tubulin from Trypanosoma evansi induced protection against T. evansi, T. equiperdum and T. b. brucei infection in mice.

    Science.gov (United States)

    Li, S-Q; Fung, M-C; Reid, S A; Inoue, N; Lun, Z-R

    2007-04-01

    The beta-tubulin gene of Trypanosoma evansi (STIB 806) was cloned and expressed in Escherichia coli. The predicted amino acid sequence of T. evansi beta-tubulin shows 100%, 99.8%, 99.1%, and 98.6% homology with T. equiperdum, T. b. brucei, T. cruzi and T. danilewskyi, respectively, but is diverse from that of T. cyclops, showing only 51.6% of homology. Recombinant beta-tubulin was expressed as inclusion bodies in E. coli. It was purified and renatured for immunological studies. Mice immunized with the renatured recombinant beta-tubulin were protected from lethal challenge with T. evansi STIB 806, T. equiperdum STIB 818 and T. b. brucei STIB 940, showing 83.3%, 70% and 76.7% protection, respectively. Serum collected from the rabbit immunized with recombinant beta-tubulin inhibited the growth of T. evansi, T. equiperdum and T. b. brucei in vitro. Serum from mice and rabbits immunized with recombinant beta-tubulin recognized only T. evansi beta-tubulin and not mouse beta-tubulin. The results of this study demonstrated that the recombinant T. evansi beta-tubulin is a potential candidate for the development of a vaccine to prevent animal trypanosomiasis caused by these three trypanosome species.

  20. Relations Between Toddler Sleep Characteristics, Sleep Problems, and Temperament.

    Science.gov (United States)

    Molfese, Victoria J; Rudasill, Kathleen M; Prokasky, Amanda; Champagne, Carly; Holmes, Molly; Molfese, Dennis L; Bates, John E

    2015-01-01

    Two sources of information (parent-reported sleep diaries and actigraph records) were used to investigate how toddler sleep characteristics (bed time/sleep onset, wake time/sleep offset, total nighttime sleep, and total sleep time) are related to sleep problems and temperament. There were 64 toddler participants in the study. Consistent with studies of older children, parent reports differed from actigraph-based records. The findings that parent-reported and actigraph-recorded sleep characteristics varied as a function of parent report of toddler sleep problems and temperament add needed information on toddler sleep. Such information may contribute to improving parents' awareness of their child's sleep characteristics and correlates of problem sleep.

  1. A "Sleep 101" Program for College Students Improves Sleep Hygiene Knowledge and Reduces Maladaptive Beliefs about Sleep.

    Science.gov (United States)

    Kloss, Jacqueline D; Nash, Christina O; Walsh, Colleen M; Culnan, Elizabeth; Horsey, Sarah; Sexton-Radek, Kathy

    2016-01-01

    Sensitizing young adults about sleep hygiene knowledge and helpful sleep attitudes may have the potential to instill long-lasting healthy sleep practices. Towards these ends, evaluation of psychoeducational program "Sleep 101" tailored to college students was undertaken. Following two weeks of sleep-log recordings, participants were randomly assigned to a Sleep 101 (experimental) condition or a sleep monitoring (control) condition. The Sleep 101 condition was comprised of two 90-minute workshops aimed to educate students about healthy sleep practices, helpful thoughts about sleep, and ways to improve sleep. The sleep monitoring group received a sleep hygiene handout and completed sleep logs for the study duration. Sleep 101 participants endorsed fewer maladaptive beliefs and attitudes about sleep, increased sleep hygiene knowledge, and reduced sleep onset latency compared to the sleep monitoring participants. Brief psychoeducational courses may be a cost-effective way to alleviate current, and/or prevent future, sleep problems in young adults.

  2. The effects of sleep extension on sleep and cognitive performance in adolescents with chronic sleep reduction: an experimental study

    NARCIS (Netherlands)

    Dewald-Kaufmann, J.F.; Oort, F.J.; Meijer, A.M.

    2013-01-01

    Objective: To investigate the effects of gradual sleep extension in adolescents with chronic sleep reduction. Outcome variables were objectively measured sleep and cognitive performance. Methods: Participants were randomly assigned to either a sleep extension group (gradual sleep extension by

  3. Sleep, Cognition and Dementia.

    Science.gov (United States)

    Porter, Verna R; Buxton, William G; Avidan, Alon Y

    2015-12-01

    The older patient population is growing rapidly around the world and in the USA. Almost half of seniors over age 65 who live at home are dissatisfied with their sleep, and nearly two-thirds of those residing in nursing home facilities suffer from sleep disorders. Chronic and pervasive sleep complaints and disturbances are frequently associated with excessive daytime sleepiness and may result in impaired cognition, diminished intellect, poor memory, confusion, and psychomotor retardation all of which may be misinterpreted as dementia. The key sleep disorders impacting patients with dementia include insomnia, hypersomnolence, circadian rhythm misalignment, sleep disordered breathing, motor disturbances of sleep such as periodic leg movement disorder of sleep and restless leg syndrome, and parasomnias, mostly in the form of rapid eye movement (REM) sleep behavior disorder (RBD). RBD is a pre-clinical marker for a class of neurodegenerative diseases, the "synucleinopathies", and requires formal polysomnographic evaluation. Untreated sleep disorders may exacerbate cognitive and behavioral symptoms in patients with dementia and are a source of considerable stress for bed partners and family members. When left untreated, sleep disturbances may also increase the risk of injury at night, compromise health-related quality of life, and precipitate and accelerate social and economic burdens for caregivers.

  4. [Placebo analgesia and sleep].

    Science.gov (United States)

    Chouchou, F; Lavigne, G-J

    2014-10-01

    The placebo response is a psychobiological phenomenon for clinical benefits following the administration of an inert substance whatever its form. This phenomenon can be attributed to a wide range of neurobiological processes, such as expectations of relief, the Pavlovian conditioning and learning, emotional regulation, and reward mechanisms, which are themselves under the influence of processes that take place during sleep. The study of placebo analgesia in healthy from a placebo conditioning associated with analgesic suggestions has highlighted a relationship between sleep, expectations of relief and placebo analgesia: when the induction is persuasive before sleep, expectations of relief modulate placebo response the next morning and paradoxical sleep correlates negatively with both expectations and the placebo response. When the analgesic experience before sleep is less persuasive, expectations of relief are still present but no longer interact with placebo analgesia while paradoxical sleep no longer correlates with the analgesic placebo response. Sleep-processes especially during paradoxical sleep seem to influence the relationship between expectations of relief and placebo analgesia. In this review, we describe the relationship between sleep and placebo analgesia, the mechanisms involved in the placebo response (e.g., conditioning, learning, memory, reward) and their potential link with sleep that could make it a special time for the building placebo response. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  5. Sleep and vascular disorders.

    Science.gov (United States)

    Plante, Gérard E

    2006-10-01

    It is not surprising that cardiovascular diseases such as congestive heart failure and coronary insufficiency can give rise to varying degrees of sleep impairment; it is less readily appreciated that certain physiologic events occurring during sleep-as well as long-term unsatisfactory sleep-may cause or increase the risk of cardiovascular conditions such as hypertension, atherosclerosis, stroke, and cardiac arrythmias. Heart rate abnormalities during sleep in normotensive subjects predict later cardiovascular disease, and their early identification alerts the physician to undertake preventive measures. Maneuvers, such as induction of hypoxia, can elicit abnormal blood pressure responses during sleep, and such responses have been used to identify impending cardiovascular problems that could become therapeutic targets. The spontaneously hypertensive rat has been used to examine the effect of sympathetic nervous system (SNS) activity on the heart under a variety of experimental conditions, including quiet and paradoxical sleep. The results have disclosed significant differences between the responses of spontaneously hypertensive rats and normal rats to SNS stimulation. Exploration of other pathophysiologic pathways affected by exposure to light and dark, including those responsive to the cyclic production of melatonin, will improve our understanding of the effect of disruptions of the circadian cycle on cardiovascular function. There is growing evidence that melatonin can influence important processes such as fluid, nitrogen, and acid-base balance. Human subjects whose nocturnal arterial blood pressure fails to show the "normal" decrement during sleep ("nondippers") are also prone to sleep poorly, exhibit increased SNS activity during sleep, and have an increased risk of total and cardiovascular disease mortality. Chronic sleep deficit is now known to be a risk factor for obesity and may contribute to the visceral form of obesity that underlies the metabolic syndrome

  6. Association Between Sleep Hygiene and Sleep Quality in Medical Students

    OpenAIRE

    Brick, Cameron A.; Seely, Darbi L.; Palermo, Tonya M.

    2010-01-01

    The aim of this study was to determine whether subjective sleep quality was reduced in medical students, and whether demographics and sleep hygiene behaviors were associated with sleep quality. A Web-based survey was completed by 314 medical students, containing questions about demographics, sleep habits, exercise habits, caffeine, tobacco and alcohol use, and subjective sleep quality (using the Pittsburgh Sleep Quality Index). Correlation and regression analyses tested for associations among...

  7. Sleep Tips: 7 Steps to Better Sleep

    Science.gov (United States)

    ... uptodate.com/home. Accessed April 7, 2017. Sleep deprivation and deficiency. National Heart, Lung, and Blood Institute. ... Mayo Clinic Footer Legal Conditions and Terms Any use of this site constitutes your agreement to the ...

  8. Pathology of sleep, hormones and depression

    NARCIS (Netherlands)

    Steiger, A.; Dresler, M.; Kluge, M.; Schussler, P.

    2013-01-01

    In patients with depression, characteristic changes of sleep electroencephalogram and nocturnal hormone secretion occur including rapid eye movement (REM) sleep disinhibition, reduced non-REM sleep and impaired sleep continuity. Neuropeptides are common regulators of the sleep electroencephalogram

  9. Antioxidant defense responses to sleep loss and sleep recovery

    National Research Council Canada - National Science Library

    Carol A. Everson; Christa D. Laatsch; Neil Hogg

    .... Sleep deprivation in the animal model produces a condition that eventually becomes highly lethal, lacks specific localization, and is reversible with sleep, implying mediation by a biochemical abnormality...

  10. Sleep Health: Reciprocal Regulation of Sleep and Innate Immunity

    National Research Council Canada - National Science Library

    Irwin, Michael R; Opp, Mark R

    2017-01-01

    ...://www.neuropsychopharmacologyreviews.org Web End =www.neuropsychopharmacologyreviews.org 129 Sleep Health: Reciprocal Regulation of Sleep and Innate Immunity [notdef][notdef][notdef][notdef][notdef...

  11. Sleep and sleep disorders in children and adolescents.

    Science.gov (United States)

    Meltzer, Lisa J; Mindell, Jodi A

    2006-12-01

    Pediatric sleep disorders are common, affecting approximately 25% to 40% of children and adolescents. Although there are several different types of sleep disorders that affect youth, each disorder can have a significant impact on daytime functioning and development, including learning, growth, behavior, and emotion regulation. Researchers are only beginning to uncover the interaction between sleep and psychiatric disorders in children and adolescents, including depression, attention-deficit/hyperactivity disorder, and autism. This article reviews normal sleep and sleep disorders in children and adolescents, the assessment of sleep in pediatric populations, common pediatric sleep disorders, and sleep in children who have common psychiatric disorders.

  12. Are You Getting Enough Sleep?

    Science.gov (United States)

    ... Submit Button Past Emails Are you getting enough sleep? Recommend on Facebook Tweet Share Compartir Learn how ... more sleep than adults. Habits to improve your sleep There are some important habits that can improve ...

  13. Cutaneous warming promotes sleep onset

    National Research Council Canada - National Science Library

    Roy J. E. M. Raymann; Dick F. Swaab; Eus J. W. Van Someren

    2005-01-01

    Sleep occurs in close relation to changes in body temperature. Both the monophasic sleep period in humans and the polyphasic sleep periods in rodents tend to be initiated when core body temperature is declining...

  14. Sleep disorders in the elderly

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000064.htm Sleep disorders in older adults To use the sharing features on this page, please enable JavaScript. Sleep disorders in older adults involve any disrupted sleep pattern. ...

  15. Sleep in cluster headache

    DEFF Research Database (Denmark)

    Barloese, M C J; Jennum, P J; Lund, N T

    2015-01-01

    BACKGROUND AND PURPOSE: Cluster headache (CH) is a primary headache disorder characterized by severe attacks of unilateral pain following a chronobiological pattern. There is a close connection with sleep as most attacks occur during sleep. Hypothalamic involvement and a particular association...... with rapid eye movement (REM) sleep have been suggested. Sleep in a large, well-characterized population of CH patients was investigated. METHODS: Polysomnography (PSG) was performed on two nights in 40 CH patients during active bout and one night in 25 age, sex and body mass index matched controls...... in hospital. Macrostructure and other features of sleep were analyzed and related to phenotype. Clinical headache characterization was obtained by semi-structured interview. RESULTS: Ninety-nine nights of PSG were analyzed. Findings included a reduced percentage of REM sleep (17.3% vs. 23.0%, P = 0...

  16. Antitrypanosomal compounds from the essential oil and extracts of Keetia leucantha leaves with inhibitor activity on Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase.

    Science.gov (United States)

    Bero, J; Beaufay, C; Hannaert, V; Hérent, M-F; Michels, P A; Quetin-Leclercq, J

    2013-02-15

    Keetia leucantha is a West African tree used in traditional medicine to treat several diseases among which parasitic infections. The dichloromethane extract of leaves was previously shown to possess growth-inhibitory activities on Plasmodium falciparum, Trypanosoma brucei brucei and Leishmania mexicana mexicana with low or no cytotoxicity (>100 μg/ml on human normal fibroblasts) (Bero et al. 2009, 2011). In continuation of our investigations on the antitrypanosomal compounds from this dichloromethane extract, we analyzed by GC-FID and GC-MS the essential oil of its leaves obtained by hydrodistillation and the major triterpenic acids in this extract by LC-MS. Twenty-seven compounds were identified in the oil whose percentages were calculated using the normalization method. The essential oil, seven of its constituents and the three triterpenic acids were evaluated for their antitrypanosomal activity on Trypanosoma brucei brucei bloodstream forms (Tbb BSF) and procyclic forms (Tbb PF) to identify an activity on the glycolytic process of trypanosomes. The oil showed an IC(50) of 20.9 μg/ml on Tbb BSF and no activity was observed on Tbb PF. The best antitrypanosomal activity was observed for ursolic acid with IC(50) of 2.5 and 6.5 μg/ml respectively on Tbb BSF and Tbb PF. The inhibitory activity on a glycolytic enzyme of T. brucei, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), was also evaluated for betulinic acid, olenaolic acid, ursolic acid, phytol, α-ionone and β-ionone. The three triterpenic acids and β-ionone showed inhibitory activities on GAPDH with oleanolic acid being the most active with an inhibition of 72.63% at 20 μg/ml. This paper reports for the first time the composition and antitrypanosomal activity of the essential oil of Keetia leucantha. Several of its constituents and three triterpenic acids present in the dichloromethane leaves extract showed a higher antitrypanosomal activity on bloodstream forms of Tbb as compared to procyclic forms

  17. Neurobiological Consequences of Sleep Deprivation

    OpenAIRE

    Alkadhi, Karim; Zagaar, Munder; Alhaider, Ibrahim; Salim, Samina; Aleisa, Abdulaziz

    2013-01-01

    Although the physiological function of sleep is not completely understood, it is well documented that it contributes significantly to the process of learning and memory. Ample evidence suggests that adequate sleep is essential for fostering connections among neuronal networks for memory consolidation in the hippocampus. Sleep deprivation studies are extremely valuable in understanding why we sleep and what are the consequences of sleep loss. Experimental sleep deprivation in animals allows us...

  18. Exercise Effects on Sleep Physiology

    OpenAIRE

    Uchida, Sunao; Shioda, Kohei; Morita, Yuko; Kubota, Chie; Ganeko, Masashi; Takeda, Noriko

    2012-01-01

    This mini-review focuses on the effects of exercise on sleep. In its early days, sleep research largely focused on central nervous system (CNS) physiology using standardized tabulations of several sleep-specific landmark electroencephalogram (EEG) waveforms. Though coarse, this method has enabled the observation and inspection of numerous uninterrupted sleep phenomena. The research on the effects of exercise on sleep began, in the 1960s, with a focus primarily on sleep related EEG changes (CN...

  19. Circadian rhythm sleep disorders

    OpenAIRE

    Morgenthaler TI; Auger RR; Kolla BP

    2012-01-01

    Bhanu P Kolla,1,2 R Robert Auger,1,2 Timothy I Morgenthaler11Mayo Center for Sleep Medicine, 2Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN, USAAbstract: Misalignment between endogenous circadian rhythms and the light/dark cycle can result in pathological disturbances in the form of erratic sleep timing (irregular sleep–wake rhythm), complete dissociation from the light/dark cycle (circadian rhythm sleep disorder, free-running type), delayed...

  20. Sleep Disorders: Insomnia.

    Science.gov (United States)

    Burman, Deepa

    2017-09-01

    Insomnia is the most common type of sleep disorder in the family medicine population. It is defined as a persistent difficulty initiating or maintaining sleep, or a report of nonrestorative sleep, accompanied by related daytime impairment. Insomnia is a significant public health problem because of its high prevalence and management challenges. There is increasing evidence of a strong association between insomnia and various medical and psychiatric comorbidities. Diagnosis of insomnia and treatment planning rely on a thorough sleep history to address contributing and precipitating factors as well as maladaptive behaviors resulting in poor sleep. Using a sleep diary or sleep log is more accurate than patient recall to determine sleep patterns. A sleep study is not routinely indicated for evaluation of insomnia. Cognitive behavioral therapy for insomnia (CBT-I) is the mainstay of treatment and is a safe and effective approach. The key challenge of CBT-I is the lack of clinicians to implement it. The newer generation nonbenzodiazepines (eg, zolpidem, zaleplon) are used as first-line pharmacotherapy for chronic insomnia. Newer drugs active on targets other than the gamma-aminobutyric acid receptor are now available, but clear treatment guidelines are needed. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  1. Headaches and sleep disorders.

    Science.gov (United States)

    Freedom, Thomas

    2015-06-01

    Headaches and sleep disorders are associated in a complex manner. Both the disorders are common in the general population, but the relationship between the two is more than coincidental. Sleep disorders can exacerbate headache sand the converse is also true. Treatment of sleep disorders can have a positive impact on the treatment of headaches. Screening for sleep disorders should be considered in all patients with headaches. This can be accomplished with brief screening tools. Those who screen positively can be further evaluated or referred to asleep specialist.

  2. Sleep inspires insight.

    Science.gov (United States)

    Wagner, Ullrich; Gais, Steffen; Haider, Hilde; Verleger, Rolf; Born, Jan

    2004-01-22

    Insight denotes a mental restructuring that leads to a sudden gain of explicit knowledge allowing qualitatively changed behaviour. Anecdotal reports on scientific discovery suggest that pivotal insights can be gained through sleep. Sleep consolidates recent memories and, concomitantly, could allow insight by changing their representational structure. Here we show a facilitating role of sleep in a process of insight. Subjects performed a cognitive task requiring the learning of stimulus-response sequences, in which they improved gradually by increasing response speed across task blocks. However, they could also improve abruptly after gaining insight into a hidden abstract rule underlying all sequences. Initial training establishing a task representation was followed by 8 h of nocturnal sleep, nocturnal wakefulness, or daytime wakefulness. At subsequent retesting, more than twice as many subjects gained insight into the hidden rule after sleep as after wakefulness, regardless of time of day. Sleep did not enhance insight in the absence of initial training. A characteristic antecedent of sleep-related insight was revealed in a slowing of reaction times across sleep. We conclude that sleep, by restructuring new memory representations, facilitates extraction of explicit knowledge and insightful behaviour.

  3. [Sleep disorder and sleep health promotion for the elderly].

    Science.gov (United States)

    Tanaka, Hideki

    2015-06-01

    The purpose of this paper is to provide an overview of the effects of the sleep health promotion. Sleep health promotion that included short naps and exercise in the evening was effective in promoting sleep with elderly people. The interventions demonstrated that the proper awakening maintenance and keeping proper arousal level during the evening were effective in improving sleep quality. Sleep health promotion that included sleep education and cognitive-behavioral interventions improved sleep-related habits and the quality of sleep. Sleep health promotion were developed. Mental and physical health were also improved along with improving sleep with the elderly. These results suggest that cognitive-behavioral interventions to improve the sleep are effective for the activity of daily living, and the quality of life.

  4. Sleep deficiency and sleep health problems in chinese adolescents.

    Science.gov (United States)

    Kang, Victor; Shao, Jesus; Zhang, Kai; Mulvey, Martha; Ming, Xue; Wagner, George C

    2012-01-01

    A survey of sleep schedules, sleep health, and the impact on school performance was conducted in 585 adolescents in a high school in China. A high level of early and circadian-disadvantaged sleep/wake schedules during weekdays was observed. Significantly shorter sleep duration on weekdays was reported (P sleep and sleepiness during weekdays were prevalent. Night awakenings were reported in 32.2% of students. Students with a sleep length of less than 7 hours, complaint of inadequate sleep, or excessive daytime sleepiness during weekdays were more likely to report an adverse effect of poor sleep on performance. The present observations are qualitatively similar to those reported in our study in American adolescents, particularly with respect to Chinese adolescents exhibiting a similar sleep deficiency on weekdays. We concluded that sleep deficiency and sleep health problems were prevalent in the participating adolescents in China, and were perceived to adversely affect school performance.

  5. To sleep or not to sleep: the ecology of sleep in artificial organisms

    OpenAIRE

    Nunn Charles L; McNamara Patrick; Acerbi Alberto

    2008-01-01

    Abstract Background All animals thus far studied sleep, but little is known about the ecological factors that generate differences in sleep characteristics across species, such as total sleep duration or division of sleep into multiple bouts across the 24-hour period (i.e., monophasic or polyphasic sleep activity). Here we address these questions using an evolutionary agent-based model. The model is spatially explicit, with food and sleep sites distributed in two clusters on the landscape. Ag...

  6. Effect of Daytime Exercise on Sleep Eeg and Subjective Sleep

    Science.gov (United States)

    Sasazawa, Y.; Kawada, T.; Kiryu, Y.

    1997-08-01

    This study was designed to assess the effects of daytime physical exercise on the quality of objective and subjective sleep by examining all-night sleep EEGs. The subjects were five male students, aged 19 to 20 years, who were in the habit of performing regular daytime exercise. The sleep polygraphic parameters in this study were sleep stage time as a percentage of total sleep time (%S1, %S2, %S(3+4), %SREM, %MT), time in bed (TIB), sleep time (ST), total sleep time (TST), sleep onset latency (SOL), waking from sleep, sleep efficiency, number of awakenings, number of stage shifts, number of spindles, and percentages of α and δ waves, all of which were determined by an automatic computer analysis system. The OSA questionnaire was used to investigate subjective sleep. The five scales of the OSA used were sleepiness, sleep maintenance, worry, integrated sleep feeling, and sleep initiation. Each sleep parameter was compared in the exercise and the non-exercise groups. Two-way analysis of variance was applied using subject factor and exercise factor. The main effect of the subject was significant in all parameters and the main effect of exercise in %S(3+4), SOL and sleep efficiency, among the objective sleep parameters. The main effects of the subject, except sleepiness, were significant, as was the main effect of exercise on sleep initiation, among the subjective sleep parameters. These findings suggest that daytime exercise shortened sleep latency and prolonged slow-wave sleep, and that the subjects fell asleep more easily on exercise days. There were also significant individual differences in both the objective and subjective sleep parameters.

  7. Unihemispheric sleep and asymmetrical sleep: behavioral, neurophysiological, and functional perspectives

    Directory of Open Access Journals (Sweden)

    Mascetti GG

    2016-07-01

    Full Text Available Gian Gastone Mascetti Department of General Psychology, University of Padova, Padova, Italy Abstract: Sleep is a behavior characterized by a typical body posture, both eyes' closure, raised sensory threshold, distinctive electrographic signs, and a marked decrease of motor activity. In addition, sleep is a periodically necessary behavior and therefore, in the majority of animals, it involves the whole brain and body. However, certain marine mammals and species of birds show a different sleep behavior, in which one cerebral hemisphere sleeps while the other is awake. In dolphins, eared seals, and manatees, unihemispheric sleep allows them to have the benefits of sleep, breathing, thermoregulation, and vigilance. In birds, antipredation vigilance is the main function of unihemispheric sleep, but in domestic chicks, it is also associated with brain lateralization or dominance in the control of behavior. Compared to bihemispheric sleep, unihemispheric sleep would mean a reduction of the time spent sleeping and of the associated recovery processes. However, the behavior and health of aquatic mammals and birds does not seem at all impaired by the reduction of sleep. The neural mechanisms of unihemispheric sleep are unknown, but assuming that the neural structures involved in sleep in cetaceans, seals, and birds are similar to those of terrestrial mammals, it is suggested that they involve the interaction of structures of the hypothalamus, basal forebrain, and brain stem. The neural mechanisms promoting wakefulness dominate one side of the brain, while those promoting sleep predominates the other side. For cetaceans, unihemispheric sleep is the only way to sleep, while in seals and birds, unihemispheric sleep events are intermingled with bihemispheric and rapid eye movement sleep events. Electroencephalogram hemispheric asymmetries are also reported during bihemispheric sleep, at awakening, and at sleep onset, as well as being associated with a use

  8. Circadian regulation of sleep and the sleep EEG under constant sleep pressure in the rat.

    Science.gov (United States)

    Yasenkov, Roman; Deboer, Tom

    2010-05-01

    Sleep is regulated by homeostatic and circadian processes. Slow wave activity (SWA; 1-4 Hz) in the NREM sleep electroencephalogram (EEG) reflects sleep homeostasis. Activity of faster EEG frequencies (10-25 Hz) is thought to be under influence of circadian factors. The relative contribution of both processes to the distribution of sleep and wakefulness and EEG activity in rodents remains uncertain. Continuous EEG recording in rats in constant dark conditions (DD) were performed and a sleep deprivation protocol consisting of 2 h sleep deprivation followed by 2 h of rest (2h/2h) was applied for 48 h to obtain a constant sleep pressure. Basic sleep research laboratory. Adult male Wistar rats. Sleep deprivation. Under the 2h/2h protocol, the circadian modulation of waking, NREM and REM sleep was markedly reduced compared to the baseline, affecting the frequency of vigilance state episodes and the duration of REM sleep and waking episodes. In contrast, NREM sleep episode duration still showed a daily modulation. Consecutive 2h values of SWA in NREM sleep were stabile during the 2h\\2h protocol, while NREM sleep EEG activity within the higher frequencies (7-25 Hz) still demonstrated strong circadian modulation, which did not differ from baseline. In rats, the daily modulation of REM sleep is less pronounced compared to NREM sleep and waking. In contrast to SWA, activity in higher frequencies (7-25 Hz) in the NREM sleep EEG have an endogenous circadian origin and are not influenced by sleep homeostatic mechanisms.

  9. Molecular bases of cytoskeleton plasticity during the Trypanosoma brucei parasite cycle.

    Science.gov (United States)

    Rotureau, Brice; Subota, Ines; Bastin, Philippe

    2011-05-01

    African trypanosomes are flagellated protozoan parasites responsible for sleeping sickness and transmitted by tsetse flies. The accomplishment of their parasite cycle requires adaptation to highly diverse environments. These transitions take place in a strictly defined order and are accompanied by spectacular morphological modifications in cell size, shape and positioning of organelles. To understand the molecular bases of these processes, parasites isolated from different tissues of the tsetse fly were analysed by immunofluorescence with markers for specific cytoskeleton components and by a new immunofluorescence-based assay for evaluation of the cell volume. The data revealed striking differences between proliferative stages found in the midgut or in the salivary glands and the differentiating stage occurring in the proventriculus. Cell proliferation was characterized by a significant increase in cell volume, by a pronounced cell elongation marked by microtubule extension at the posterior end, and by the production of a new flagellum similar to the existing one. In contrast, the differentiating stage found in the proventriculus does not display any increase in cell volume neither in cell length, but is marked by a profound remodelling of the posterior part of the cytoskeleton and by changes in molecular composition and/or organization of the flagellum attachment zone. © 2011 Blackwell Publishing Ltd.

  10. Neurobiological Consequences of Sleep Deprivation

    Science.gov (United States)

    Alkadhi, Karim; Zagaar, Munder; Alhaider, Ibrahim; Salim, Samina; Aleisa, Abdulaziz

    2013-01-01

    Although the physiological function of sleep is not completely understood, it is well documented that it contributes significantly to the process of learning and memory. Ample evidence suggests that adequate sleep is essential for fostering connections among neuronal networks for memory consolidation in the hippocampus. Sleep deprivation studies are extremely valuable in understanding why we sleep and what are the consequences of sleep loss. Experimental sleep deprivation in animals allows us to gain insight into the mechanism of sleep at levels not possible to study in human subjects. Many useful approaches have been utilized to evaluate the effect of sleep loss on cognitive function, each with relative advantages and disadvantages. In this review we discuss sleep and the detrimental effects of sleep deprivation mostly in experimental animals. The negative effects of sleep deprivation on various aspects of brain function including learning and memory, synaptic plasticity and the state of cognition-related signaling molecules are discussed. PMID:24179461

  11. Neurobiological consequences of sleep deprivation.

    Science.gov (United States)

    Alkadhi, Karim; Zagaar, Munder; Alhaider, Ibrahim; Salim, Samina; Aleisa, Abdulaziz

    2013-05-01

    Although the physiological function of sleep is not completely understood, it is well documented that it contributes significantly to the process of learning and memory. Ample evidence suggests that adequate sleep is essential for fostering connections among neuronal networks for memory consolidation in the hippocampus. Sleep deprivation studies are extremely valuable in understanding why we sleep and what are the consequences of sleep loss. Experimental sleep deprivation in animals allows us to gain insight into the mechanism of sleep at levels not possible to study in human subjects. Many useful approaches have been utilized to evaluate the effect of sleep loss on cognitive function, each with relative advantages and disadvantages. In this review we discuss sleep and the detrimental effects of sleep deprivation mostly in experimental animals. The negative effects of sleep deprivation on various aspects of brain function including learning and memory, synaptic plasticity and the state of cognition-related signaling molecules are discussed.

  12. Probing the metabolic network in bloodstream-form Trypanosoma brucei using untargeted metabolomics with stable isotope labelled glucose.

    Directory of Open Access Journals (Sweden)

    Darren J Creek

    2015-03-01

    Full Text Available Metabolomics coupled with heavy-atom isotope-labelled glucose has been used to probe the metabolic pathways active in cultured bloodstream form trypomastigotes of Trypanosoma brucei, a parasite responsible for human African trypanosomiasis. Glucose enters many branches of metabolism beyond glycolysis, which has been widely held to be the sole route of glucose metabolism. Whilst pyruvate is the major end-product of glucose catabolism, its transamination product, alanine, is also produced in significant quantities. The oxidative branch of the pentose phosphate pathway is operative, although the non-oxidative branch is not. Ribose 5-phosphate generated through this pathway distributes widely into nucleotide synthesis and other branches of metabolism. Acetate, derived from glucose, is found associated with a range of acetylated amino acids and, to a lesser extent, fatty acids; while labelled glycerol is found in many glycerophospholipids. Glucose also enters inositol and several sugar nucleotides that serve as precursors to macromolecule biosynthesis. Although a Krebs cycle is not operative, malate, fumarate and succinate, primarily labelled in three carbons, were present, indicating an origin from phosphoenolpyruvate via oxaloacetate. Interestingly, the enzyme responsible for conversion of phosphoenolpyruvate to oxaloacetate, phosphoenolpyruvate carboxykinase, was shown to be essential to the bloodstream form trypanosomes, as demonstrated by the lethal phenotype induced by RNAi-mediated downregulation of its expression. In addition, glucose derivatives enter pyrimidine biosynthesis via oxaloacetate as a precursor to aspartate and orotate.

  13. Flagellar adhesion in Trypanosoma brucei relies on interactions between different skeletal structures in the flagellum and cell body.

    Science.gov (United States)

    Rotureau, Brice; Blisnick, Thierry; Subota, Ines; Julkowska, Daria; Cayet, Nadège; Perrot, Sylvie; Bastin, Philippe

    2014-01-01

    The Trypanosoma brucei flagellum is an essential organelle anchored along the surface of the cell body through a specialized structure called the flagellum attachment zone (FAZ). Adhesion relies on the interaction of the extracellular portion of two transmembrane proteins, FLA1 and FLA1BP. Here, we identify FLAM3 as a novel large protein associated with the flagellum skeleton whose ablation inhibits flagellum attachment. FLAM3 does not contain transmembrane domains and its flagellar localization matches closely, but not exactly, that of the paraflagellar rod, an extra-axonemal structure present in the flagellum. Knockdown of FLA1 or FLAM3 triggers similar defects in motility and morphogenesis, characterized by the assembly of a drastically reduced FAZ filament. FLAM3 remains associated with the flagellum skeleton even in the absence of adhesion or a normal paraflagellar rod. However, the protein is dispersed in the cytoplasm when flagellum formation is inhibited. By contrast, FLA1 remains tightly associated with the FAZ filament even in the absence of a flagellum. In these conditions, the extracellular domain of FLA1 points to the cell surface. FLAM3 is essential for proper distribution of FLA1BP, which is restricted to the most proximal portion of the flagellum upon knockdown of FLAM3. We propose that FLAM3 is a key component of the FAZ connectors that link the axoneme to the adhesion zone, hence it acts in an equivalent manner to the FAZ filament complex, but on the side of the flagellum.

  14. A global comparison of the human and T. brucei degradomes gives insights about possible parasite drug targets.

    Directory of Open Access Journals (Sweden)

    Susan T Mashiyama

    Full Text Available We performed a genome-level computational study of sequence and structure similarity, the latter using crystal structures and models, of the proteases of Homo sapiens and the human parasite Trypanosoma brucei. Using sequence and structure similarity networks to summarize the results, we constructed global views that show visually the relative abundance and variety of proteases in the degradome landscapes of these two species, and provide insights into evolutionary relationships between proteases. The results also indicate how broadly these sequence sets are covered by three-dimensional structures. These views facilitate cross-species comparisons and offer clues for drug design from knowledge about the sequences and structures of potential drug targets and their homologs. Two protease groups ("M32" and "C51" that are very different in sequence from human proteases are examined in structural detail, illustrating the application of this global approach in mining new pathogen genomes for potential drug targets. Based on our analyses, a human ACE2 inhibitor was selected for experimental testing on one of these parasite proteases, TbM32, and was shown to inhibit it. These sequence and structure data, along with interactive versions of the protein similarity networks generated in this study, are available at http://babbittlab.ucsf.edu/resources.html.

  15. Similarity in variable antigen type composition of Trypanosoma brucei rhodesiense populations in different sites within the mouse host.

    Science.gov (United States)

    Turner, C M; Hunter, C A; Barry, J D; Vickerman, K

    1986-01-01

    Trypanosoma brucei rhodesiense subpopulations in different sites within the body of infected mice were isolated and enumerated on day 6 of cyclically transmitted infections. Most trypanosomes were in the blood vasculature and spleen but approximately 6% occurred in lymph nodes and about 9% were extravascular. Most of the extravascular trypanosomes were in the peritoneal and pleural cavities; significant numbers also occurred in the brain and kidneys. Six major variable antigen types (VATs) were detected by immunofluorescence using specific antisera and monoclonal antibodies. The prevalence of each VAT was essentially the same in subpopulations in the blood, mesenteric and inguinal lymph nodes, brain, kidneys and peritoneal and pleural cavities. This similarity of VAT composition in different subpopulations is probably caused by high rates of dynamic interchange of trypanosomes between sites. Extravascular trypanosomes, therefore, form a significant proportion of the total population in acute infections of mice but they do not appear to play any special role in the population biology of antigenic variation at this stage of infection.

  16. Disrupted Nighttime Sleep in Narcolepsy

    Science.gov (United States)

    Roth, Thomas; Dauvilliers, Yves; Mignot, Emmanuel; Montplaisir, Jacques; Paul, Josh; Swick, Todd; Zee, Phyllis

    2013-01-01

    Study Objectives: Characterize disrupted nighttime sleep (DNS) in narcolepsy, an important symptom of narcolepsy. Methods: A panel of international narcolepsy experts was convened in 2011 to build a consensus characterization of DNS in patients with narcolepsy. A literature search of the Medline (1965 to date), Medline In-Process (latest weeks), Embase (1974 to date), Embase Alert (latest 8 weeks), and Biosis (1965 to date) databases was conducted using the following search terms: narcolepsy and disrupted nighttime sleep, disturbed nighttime sleep, fragmented sleep, consolidated sleep, sleep disruption, and narcolepsy questionnaire. The purpose of the literature search was to identify publications characterizing the nighttime sleep of patients with narcolepsy. The panel reviewed the literature. Nocturnal sleep can also be disturbed by REM sleep abnormalities such as vivid dreaming and REM sleep behavior disorder; however, these were not reviewed in the current paper, as we were evaluating for idiopathic sleep disturbances. Results: The literature reviewed provide a consistent characterization of nighttime sleep in patients with narcolepsy as fragmented, with reports of frequent, brief nightly awakenings with difficulties returning to sleep and associated reports of poor sleep quality. Polysomnographic studies consistently report frequent awakenings/arousals after sleep onset, more stage 1 (S1) sleep, and more frequent shifts to S1 sleep or wake from deeper stages of sleep. The consensus of the International Experts' Panel on Narcolepsy was that DNS can be distressing for patients with narcolepsy and that treatment of DNS warrants consideration. Conclusions: Clinicians involved in the management of patients with narcolepsy should investigate patients' quality of nighttime sleep, give weight and consideration to patient reports of nighttime sleep experience, and consider DNS a target for treatment. Citation: Roth T; Dauvilliers Y; Mignot E; Montplaisir J; Paul J

  17. Unihemispheric sleep and asymmetrical sleep: behavioral, neurophysiological, and functional perspectives.

    Science.gov (United States)

    Mascetti, Gian Gastone

    2016-01-01

    Sleep is a behavior characterized by a typical body posture, both eyes' closure, raised sensory threshold, distinctive electrographic signs, and a marked decrease of motor activity. In addition, sleep is a periodically necessary behavior and therefore, in the majority of animals, it involves the whole brain and body. However, certain marine mammals and species of birds show a different sleep behavior, in which one cerebral hemisphere sleeps while the other is awake. In dolphins, eared seals, and manatees, unihemispheric sleep allows them to have the benefits of sleep, breathing, thermoregulation, and vigilance. In birds, antipredation vigilance is the main function of unihemispheric sleep, but in domestic chicks, it is also associated with brain lateralization or dominance in the control of behavior. Compared to bihemispheric sleep, unihemispheric sleep would mean a reduction of the time spent sleeping and of the associated recovery processes. However, the behavior and health of aquatic mammals and birds does not seem at all impaired by the reduction of sleep. The neural mechanisms of unihemispheric sleep are unknown, but assuming that the neural structures involved in sleep in cetaceans, seals, and birds are similar to those of terrestrial mammals, it is suggested that they involve the interaction of structures of the hypothalamus, basal forebrain, and brain stem. The neural mechanisms promoting wakefulness dominate one side of the brain, while those promoting sleep predominates the other side. For cetaceans, unihemispheric sleep is the only way to sleep, while in seals and birds, unihemispheric sleep events are intermingled with bihemispheric and rapid eye movement sleep events. Electroencephalogram hemispheric asymmetries are also reported during bihemispheric sleep, at awakening, and at sleep onset, as well as being associated with a use-dependent process (local sleep).

  18. BDNF in sleep, insomnia, and sleep deprivation.

    Science.gov (United States)

    Schmitt, Karen; Holsboer-Trachsler, Edith; Eckert, Anne

    2016-01-01

    The protein brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors involved in plasticity of neurons in several brain regions. There are numerous evidence that BDNF expression is decreased by experiencing psychological stress and that, accordingly, a lack of neurotrophic support causes major depression. Furthermore, disruption in sleep homeostatic processes results in higher stress vulnerability and is often associated with stress-related mental disorders. Recently, we reported, for the first time, a relationship between BDNF and insomnia and sleep deprivation (SD). Using a biphasic stress model as explanation approach, we discuss here the hypothesis that chronic stress might induce a deregulation of the hypothalamic-pituitary-adrenal system. In the long-term it leads to sleep disturbance and depression as well as decreased BDNF levels, whereas acute stress like SD can be used as therapeutic intervention in some insomniac or depressed patients as compensatory process to normalize BDNF levels. Indeed, partial SD (PSD) induced a fast increase in BDNF serum levels within hours after PSD which is similar to effects seen after ketamine infusion, another fast-acting antidepressant intervention, while traditional antidepressants are characterized by a major delay until treatment response as well as delayed BDNF level increase. Key messages Brain-derived neurotrophic factor (BDNF) plays a key role in the pathophysiology of stress-related mood disorders. The interplay of stress and sleep impacts on BDNF level. Partial sleep deprivation (PSD) shows a fast action on BDNF level increase.

  19. [The NHG guideline 'Sleep problems and sleeping pills'

    NARCIS (Netherlands)

    Damen-van Beek, Z.; Lucassen, P.L.; Gorgels, W.J.M.J.; Smelt, A.F.; Knuistingh Neven, A.; Bouma, M.

    2015-01-01

    - The Dutch College of General Practitioners' (NHG) guideline 'Sleep problems and sleeping pills' provides recommendations for the diagnosis and treatment of the most prevalent sleep problems and for the management of chronic users of sleeping pills.- The preferred approach for sleeplessness is not

  20. Shining evolutionary light on human sleep and sleep disorders.

    Science.gov (United States)

    Nunn, Charles L; Samson, David R; Krystal, Andrew D

    2016-01-01

    Sleep is essential to cognitive function and health in humans, yet the ultimate reasons for sleep-i.e. 'why' sleep evolved-remain mysterious. We integrate findings from human sleep studies, the ethnographic record, and the ecology and evolution of mammalian sleep to better understand sleep along the human lineage and in the modern world. Compared to other primates, sleep in great apes has undergone substantial evolutionary change, with all great apes building a sleeping platform or 'nest'. Further evolutionary change characterizes human sleep, with humans having the shortest sleep duration, yet the highest proportion of rapid eye movement sleep among primates. These changes likely reflect that our ancestors experienced fitness benefits from being active for a greater portion of the 24-h cycle than other primates, potentially related to advantages arising from learning, socializing and defending against predators and hostile conspecifics. Perspectives from evolutionary medicine have implications for understanding sleep disorders; we consider these perspectives in the context of insomnia, narcolepsy, seasonal affective disorder, circadian rhythm disorders and sleep apnea. We also identify how human sleep today differs from sleep through most of human evolution, and the implications of these changes for global health and health disparities. More generally, our review highlights the importance of phylogenetic comparisons in understanding human health, including well-known links between sleep, cognitive performance and health in humans. © The Author(s) 2016. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

  1. Study of Sleep Habits and Sleep Problems Among Medical Students ...

    African Journals Online (AJOL)

    Background: Good quality sleep and adequate amount of sleep are important in order to have better cognitive performance and avoid health problems and psychiatric disorders. Aim: The aim of this study was to describe sleep habits and sleep problems in a population of undergraduates, interns and postgraduate students ...

  2. Sleep deprivation and depression

    NARCIS (Netherlands)

    Elsenga, Simon

    1992-01-01

    The association between depression and sleep disturbances is perhaps as old as makind. In view of the longstanding experience with this association it is amazing that only some 20 years ago, a few depressed patients attracted attention to the fact that Total Sleep Deprivation (TSD) had

  3. Obstructive Sleep Apnoea

    African Journals Online (AJOL)

    Sleep-disordered breathing (SDB) disorders include: central sleep apnoea ... cause in children). • Craniofacial abnormalities (e.g. Pierre Robin,. Down's syndrome, retrognathia, micrognathia, brachycephaly). • Neuromuscular disease. • Diabetes mellitus. ... Depression, decreased IQ and memory loss. • Increased risk of ...

  4. Genotyping sleep disorders patients.

    Science.gov (United States)

    Kripke, Daniel F; Shadan, Farhad F; Dawson, Arthur; Cronin, John W; Jamil, Shazia M; Grizas, Alexandra P; Koziol, James A; Kline, Lawrence E

    2010-03-01

    The genetic susceptibility factors underlying sleep disorders might help us predict prognoses and responses to treatment. Several candidate polymorphisms for sleep disorders have been proposed, but there has as yet inadequate replication or validation that the candidates may be useful in the clinical setting. To assess the validity of several candidate associations, we obtained saliva deoxyribonucleic acid (DNA) samples and clinical information from 360 consenting research participants who were undergoing clinical polysomnograms. Ten single nucleotide polymorphisms (SNPs) were genotyped. These were thought to be related to depression, circadian sleep disorders, sleep apnea, restless legs syndrome (RLS), excessive sleepiness, or to slow waves in sleep. With multivariate generalized linear models, the association of TEF rs738499 with depressive symptoms was confirmed. Equivocal statistical evidence of association of rs1801260 (the C3111T SNP in the CLOCK gene) with morningness/eveningness and an association of Apolipoprotein E (APOE) rs429358 with the Epworth Sleepiness Scale (ESS) were obtained, but these associations were not strong enough to be of clinical value by themselves. Predicted association of SNPs with sleep apnea, RLS, and slow wave sleep were not confirmed. The SNPs tested would not, by themselves, be of use for clinical genotyping in a sleep clinic.

  5. Obstructive sleep apnea therapy

    NARCIS (Netherlands)

    Hoekema, A.; Stegenga, B.; Wijkstra, P. J.; van der Hoeven, J. H.; Meinesz, A. F.; de Bont, L. G. M.

    In clinical practice, oral appliances are used primarily for obstructive sleep apnea patients who do not respond to continuous positive airway pressure (CPAP) therapy. We hypothesized that an oral appliance is not inferior to CPAP in treating obstructive sleep apnea effectively. We randomly assigned

  6. Stress, arousal, and sleep

    NARCIS (Netherlands)

    Sanford, Larry D.; Suchecki, Deborah; Meerlo, Peter; Meerlo, Peter; Benca, Ruth M.; Abel, Ted

    2015-01-01

    Stress is considered to be an important cause of disrupted sleep and insomnia. However, controlled and experimental studies in rodents indicate that effects of stress on sleep-wake regulation are complex and may strongly depend on the nature of the stressor. While most stressors are associated with

  7. Sleep Terrors in Twins

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2008-12-01

    Full Text Available In an attempt to clarify the genetic and environmental causes of sleep terrors in childhood, reasearchers in Canada followed 390 pairs of monozygotic and dizygotic twins by assessing the frequency of sleep terrors at 18 and 30 months of age using a questionnaire administered to the biological mothers.

  8. Sleep regulation and insomnia

    NARCIS (Netherlands)

    van Someren, E.J.W.; Cluydts, R.; Pfaff, D.W.

    2013-01-01

    For years, the subject of sleep failed to generate much interest from either the field of medicine or that of psychology - a curious fact, as a 60-year-old has spent some 20 years out of those 60 sleeping. In fact, up until the age of approximately three years, a child spends more time asleep than

  9. Nightmares and sleep terrors

    African Journals Online (AJOL)

    urinary bladder distension, a noisy environment and central nervous system depressants. This article discusses the differences between nightmares and sleep terrors and provides a management approach for the family practitioner. Introduction. Nightmares and sleep terrors are clas- sified under the parasomnias accord-.

  10. Schizophrenia, Sleep and Acupuncture

    NARCIS (Netherlands)

    Bosch, M.P.C.; Noort, M.W.M.L. van den

    2008-01-01

    This book is an introduction for professionals in Western medicine and for acupuncturists on the use of acupuncture in treatment of schizophrenia and sleep disorders. Acupuncture has long been used in Traditional Chinese Medicine (TCM) in mental health and sleep disorders. This book aims to build a

  11. Recognizing pediatric sleep apnea.

    Science.gov (United States)

    Weiss, Miriam; Owens, Judith

    2014-08-16

    Obstructive sleep apnea is a common condition in childhood and has a significant impact on health, learning, academic performance, and quality of life. The purpose of this article is to review the epidemiology, etiology, risk factors, clinical presentation, diagnostic procedures, and treatment of obstructive sleep apnea.

  12. Sleep, Exercise, and Nutrition.

    Science.gov (United States)

    Harrelson, Orvis A.; And Others

    The first part of this booklet concerns why sleep and exercise are necessary. It includes a discussion of what occurs during sleep and what dreams are. It also deals with the benefits of exercise, fatigue, posture, and the correlation between exercise and personality. The second part concerns nutrition and the importance of food. This part covers…

  13. Sleep debt and obesity.

    Science.gov (United States)

    Bayon, Virginie; Leger, Damien; Gomez-Merino, Danielle; Vecchierini, Marie-Françoise; Chennaoui, Mounir

    2014-08-01

    Short sleep duration has been shown to be associated with elevated body mass index (BMI) in many epidemiological studies. Several pathways could link sleep deprivation to weight gain and obesity, including increased food intake, decreased energy expenditure, and changes in levels of appetite-regulating hormones, such as leptin and ghrelin. A relatively new factor that is contributing to sleep deprivation is the use of multimedia (e.g. television viewing, computer, and internet), which may aggravate sedentary behavior and increase caloric intake. In addition, shift-work, long working hours, and increased time commuting to and from work have also been hypothesized to favor weight gain and obesity-related metabolic disorders, because of their strong link to shorter sleep times. This article reviews the epidemiological, biological, and behavioral evidence linking sleep debt and obesity.

  14. Sleep effects on breathing and respiratory diseases

    Directory of Open Access Journals (Sweden)

    Choudhary Sumer

    2009-01-01

    Full Text Available To understand normal sleep pattern and physiological changes during sleep, sleep and breathing interaction, nomenclature and scales used in sleep study, discuss the effect of rapid eye movements and non-rapid eye movements while sleep and to review the effects of obstructive and restrictive lung disease on gas exchange during sleep and sleep architecture.

  15. Homeostatic sleep regulation in adolescents.

    Science.gov (United States)

    Jenni, Oskar G; Achermann, Peter; Carskadon, Mary A

    2005-11-01

    To examine the effects of total sleep deprivation on adolescent sleep and the sleep electroencephalogram (EEG) and to study aspects of sleep homeostasis. Subjects were studied during baseline and recovery sleep after 36 hours of wakefulness. Four-bed sleep research laboratory. Seven prepubertal or early pubertal children (pubertal stage Tanner 1 or 2 = Tanner 1/2; mean age 11.9 years, SD +/- 0.8, 2 boys) and 6 mature adolescents (Tanner 5; 14.2 years, +/- 1.4, 2 boys). Thirty-six hours of sleep deprivation. All-night polysomnography was performed. EEG power spectra (C3/A2) were calculated using a Fast Fourier transform routine. In both groups, sleep latency was shorter, sleep efficiency was higher, non-rapid eye movement (NREM) sleep stage 4 was increased, and waking after sleep onset was reduced in recovery relative to baseline sleep. Spectral power of the NREM sleep EEG was enhanced after sleep deprivation in the low-frequency range (1.6-3.6 Hz in Tanner 1/2; 0.8-6.0 Hz in Tanner 5) and reduced in the sigma range (11-15 Hz). Sleep deprivation resulted in a stronger increase of slow-wave activity (EEG power 0.6-4.6 Hz, marker for sleep homeostatic pressure) in Tanner 5 (39% above baseline) than in Tanner 1/2 adolescents (18% above baseline). Sleep homeostasis was modeled according to the two-process model of sleep regulation. The build-up of homeostatic sleep pressure during wakefulness was slower in Tanner 5 adolescents (time constant of exponential saturating function 15.4 +/- 2.5 hours) compared with Tanner 1/2 children (8.9 +/- 1.2 hours). In contrast, the decline of the homeostatic process was similar in both groups. Maturational changes of homeostatic sleep regulation are permissive of the sleep phase delay in the course of adolescence.

  16. Sleep Deficiency and Sleep Health Problems in Chinese Adolescents

    OpenAIRE

    Victor Kang; Jesus Shao; Kai Zhang; Martha Mulvey; Xue Ming; Wagner, George C.

    2012-01-01

    A survey of sleep schedules, sleep health, and the impact on school performance was conducted in 585 adolescents in a high school in China. A high level of early and circadian-disadvantaged sleep/wake schedules during weekdays was observed. Significantly shorter sleep duration on weekdays was reported ( P < 0.0001). Older teenagers slept significantly less than the younger teenagers ( P < 0.0001). Complaints of inadequate sleep and sleepiness during weekdays were prevalent. Night awakenings w...

  17. Genetic and Immunologic Aspects of Sleep and Sleep Disorders

    OpenAIRE

    Parish, James M

    2013-01-01

    The study of genetics is providing new and exciting insights into the pathogenesis, diagnosis, and treatment of disease. Both normal sleep and several types of sleep disturbances have been found to have significant genetic influences, as have traits of normal sleep, such as those evident in EEG patterns and the circadian sleep-wake cycle. The circadian sleep-wake cycle is based on a complex feedback loop of genetic transcription over a 24-h cycle. Restless legs syndrome (RLS) and periodic lim...

  18. Sleep Deficiency and Sleep Health Problems in Chinese Adolescents

    OpenAIRE

    Victor Kang; Jesus Shao; Kai Zhang; Martha Mulvey; Xue Ming; Wagner, George C.

    2012-01-01

    A survey of sleep schedules, sleep health, and the impact on school performance was conducted in 585 adolescents in a high school in China. A high level of early and circadian-disadvantaged sleep/wake schedules during weekdays was observed. Significantly shorter sleep duration on weekdays was reported (P < 0.0001). Older teenagers slept significantly less than the younger teenagers (P < 0.0001). Complaints of inadequate sleep and sleepiness during weekdays were prevalent. Night awakenings wer...

  19. Clinical Psychology Training in Sleep and Sleep Disorders

    OpenAIRE

    Meltzer, Lisa J.; Phillips, Cindy; Mindell, Jodi A.

    2009-01-01

    There is growing evidence to suggest that clinical psychologists would benefit from more training in sleep and sleep disorders. Sleep disturbances are commonly comorbid with mental health disorders and this relationship is often bidirectional. In addition, psychologists have become integral members of multidisciplinary sleep medicine teams and there are not enough qualified psychologists to meet the clinical demand. The purpose of this study was to evaluate the current education on sleep and ...

  20. Sleep and the endocrine system.

    Science.gov (United States)

    Morgan, Dionne; Tsai, Sheila C

    2015-07-01

    In this article, the effect of sleep and sleep disorders on endocrine function and the influence of endocrine abnormalities on sleep are discussed. Sleep disruption and its associated endocrine consequences in the critically ill patient are also reviewed. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Sleep At Camp: A Survey.

    Science.gov (United States)

    Pravda, Myra

    1997-01-01

    Among 40 camp directors surveyed, the majority believed that campers get enough sleep, but that staff members and directors do not get enough sleep. Addresses how sleep deprivation can affect job performance and offers strategies for helping staff understand the importance of sleep to keep them alert and functioning in their job. Includes…

  2. Models of human sleep regulation

    NARCIS (Netherlands)

    Beersma, Domien G.M.

    1998-01-01

    Non-REM sleep deprivation and REM sleep deprivation both lead to specific rebounds, suggesting that these states fulfil physiological needs. In view of impaired performance after sleep deprivation, a recovery function of sleep seems likely. The timing of this recovery is restricted to a narrow time

  3. The Neuroprotective Aspects of Sleep.

    Science.gov (United States)

    Eugene, Andy R; Masiak, Jolanta

    2015-03-01

    Sleep is an important component of human life, yet many people do not understand the relationship between the brain and the process of sleeping. Sleep has been proven to improve memory recall, regulate metabolism, and reduce mental fatigue. A minimum of 7 hours of daily sleep seems to be necessary for proper cognitive and behavioral function. The emotional and mental handicaps associated with chronic sleep loss as well as the highly hazardous situations which can be contributed to the lack of sleep is a serious concern that people need to be aware of. When one sleeps, the brain reorganizes and recharges itself, and removes toxic waste byproducts which have accumulated throughout the day. This evidence demonstrates that sleeping can clear the brain and help maintain its normal functioning. Multiple studies have been done to determine the effects of total sleep deprivation; more recently some have been conducted to show the effects of sleep restriction, which is a much more common occurrence, have the same effects as total sleep deprivation. Each phase of the sleep cycle restores and rejuvenates the brain for optimal function. When sleep is deprived, the active process of the glymphatic system does not have time to perform that function, so toxins can build up, and the effects will become apparent in cognitive abilities, behavior, and judgment. As a background for this paper we have reviewed literature and research of sleep phases, effects of sleep deprivation, and the glymphatic system of the brain and its restorative effect during the sleep cycle.

  4. Cocaine and Sleep: Early Abstinence

    Directory of Open Access Journals (Sweden)

    Peter T. Morgan

    2007-01-01

    Full Text Available Compulsive cocaine use is associated with a profound dysregulation of sleep. Perhaps the result of chronic use, a significant deterioration in sleep is apparent over the first 3 weeks of abstinence, with no indication of recovery. Interestingly, the diminished sleep is not accompanied by subjective reports of poor or worsening sleep. Rather, subjective reports actually improve over abstinence, while sleep-related cognitive performance declines. A mechanistic understanding of the apparent difference in objective and subjective measures is currently lacking. Here we review the relevant literature on cocaine use and sleep, and discuss the possible relevance of this sleep disturbance in relationship to the underlying disorder and its treatment.

  5. Sleep Disturbances in Mood Disorders.

    Science.gov (United States)

    Rumble, Meredith E; White, Kaitlin Hanley; Benca, Ruth M

    2015-12-01

    The article provides an overview of common and differentiating self-reported and objective sleep disturbances seen in mood-disordered populations. The importance of considering sleep disturbances in the context of mood disorders is emphasized, because a large body of evidence supports the notion that sleep disturbances are a risk factor for onset, exacerbation, and relapse of mood disorders. In addition, potential mechanisms for sleep disturbance in depression, other primary sleep disorders that often occur with mood disorders, effects of antidepressant and mood-stabilizing drugs on sleep, and the adjunctive effect of treating sleep in patients with mood disorders are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Shining evolutionary light on human sleep and sleep disorders

    Science.gov (United States)

    Nunn, Charles L.; Samson, David R.; Krystal, Andrew D.

    2016-01-01

    Sleep is essential to cognitive function and health in humans, yet the ultimate reasons for sleep—i.e. ‘why’ sleep evolved—remain mysterious. We integrate findings from human sleep studies, the ethnographic record, and the ecology and evolution of mammalian sleep to better understand sleep along the human lineage and in the modern world. Compared to other primates, sleep in great apes has undergone substantial evolutionary change, with all great apes building a sleeping platform or ‘nest’. Further evolutionary change characterizes human sleep, with humans having the shortest sleep duration, yet the highest proportion of rapid eye movement sleep among primates. These changes likely reflect that our ancestors experienced fitness benefits from being active for a greater portion of the 24-h cycle than other primates, potentially related to advantages arising from learning, socializing and defending against predators and hostile conspecifics. Perspectives from evolutionary medicine have implications for understanding sleep disorders; we consider these perspectives in the context of insomnia, narcolepsy, seasonal affective disorder, circadian rhythm disorders and sleep apnea. We also identify how human sleep today differs from sleep through most of human evolution, and the implications of these changes for global health and health disparities. More generally, our review highlights the importance of phylogenetic comparisons in understanding human health, including well-known links between sleep, cognitive performance and health in humans. PMID:27470330

  7. Disrupted nighttime sleep in narcolepsy.

    Science.gov (United States)

    Roth, Thomas; Dauvilliers, Yves; Mignot, Emmanuel; Montplaisir, Jacques; Paul, Josh; Swick, Todd; Zee, Phyllis

    2013-09-15

    Characterize disrupted nighttime sleep (DNS) in narcolepsy, an important symptom of narcolepsy. A panel of international narcolepsy experts was convened in 2011 to build a consensus characterization of DNS in patients with narcolepsy. A literature search of the Medline (1965 to date), Medline In-Process (latest weeks), Embase (1974 to date), Embase Alert (latest 8 weeks), and Biosis (1965 to date) databases was conducted using the following search terms: narcolepsy and disrupted nighttime sleep, disturbed nighttime sleep, fragmented sleep, consolidated sleep, sleep disruption, and narcolepsy questionnaire. The purpose of the literature search was to identify publications characterizing the nighttime sleep of patients with narcolepsy. The panel reviewed the literature. Nocturnal sleep can also be disturbed by REM sleep abnormalities such as vivid dreaming and REM sleep behavior disorder; however, these were not reviewed in the current paper, as we were evaluating for idiopathic sleep disturbances. The literature reviewed provide a consistent characterization of nighttime sleep in patients with narcolepsy as fragmented, with reports of frequent, brief nightly awakenings with difficulties returning to sleep and associated reports of poor sleep quality. Polysomnographic studies consistently report frequent awakenings/arousals after sleep onset, more stage 1 (S1) sleep, and more frequent shifts to S1 sleep or wake from deeper stages of sleep. The consensus of the International Experts' Panel on Narcolepsy was that DNS can be distressing for patients with narcolepsy and that treatment of DNS warrants consideration. Clinicians involved in the management of patients with narcolepsy should investigate patients' quality of nighttime sleep, give weight and consideration to patient reports of nighttime sleep experience, and consider DNS a target for treatment.

  8. The Neuroprotective Aspects of Sleep

    OpenAIRE

    Eugene, Andy R.; Masiak, Jolanta

    2015-01-01

    Sleep is an important component of human life, yet many people do not understand the relationship between the brain and the process of sleeping. Sleep has been proven to improve memory recall, regulate metabolism, and reduce mental fatigue. A minimum of 7 hours of daily sleep seems to be necessary for proper cognitive and behavioral function. The emotional and mental handicaps associated with chronic sleep loss as well as the highly hazardous situations which can be contributed to the lack of...

  9. Anti-trypanosomal effect of Malva sylvestris (Malvaceae) extract on a ...

    African Journals Online (AJOL)

    Purpose: To evaluate the antitrypanosomal activity of Malva sylvestris (MS) extract in a Trypanosoma brucei brucei-infected mouse model of sleeping sickness. Methods: Sleeping sickness was induced by the intraperitoneal injection of Trypanosoma brucei brucei infected blood in mice. Confirmation of parasitaemia was ...

  10. Anti-trypanosomal effect of Malva sylvestris (Malvaceae) extract on a ...

    African Journals Online (AJOL)

    Purpose: To evaluate the antitrypanosomal activity of Malva sylvestris (MS) extract in a Trypanosoma brucei brucei-infected mouse model of sleeping sickness. Methods: Sleeping sickness was induced by the intraperitoneal injection of Trypanosoma brucei brucei- infected blood in mice. Confirmation of parasitaemia was ...

  11. Sleep Habits, Sleep Problems, Sleep Hygiene, and Their Associations With Mental Health Problems Among Adolescents.

    Science.gov (United States)

    Zhang, Jinwen; Xu, Zhiwei; Zhao, Kena; Chen, Ting; Ye, Xiuxia; Shen, Zhifei; Wu, Zengjiang; Zhang, Jun; Shen, Xiaoming; Li, Shenghui

    2017-07-01

    Studies in adults suggested that sleep could be a significant contributor to mental health. However, little is known about their relationship in adolescents. The present study aimed to examine the overall associations of full-spectrum sleep behaviors, including sleep habits, sleep problems, and sleep hygiene, with mental health problems among adolescents in Shanghai, China. A stratified, cluster random sample of 4,823 adolescents aged 11 to 20 years participated in a cross-sectional survey. The Adolescent Sleep Disturbance Questionnaire and the modified Adolescent Sleep Hygiene Scale were used to examine sleep behaviors. The Strengths and Difficulties Questionnaire was used to evaluate mental health problems. Five sleep variables were found to be associated with adolescents' mental health. The five factors covered three sleep domains: sleep habits (later bedtime during weekdays), sleep problems (maintaining sleep difficulties, disorders of arousal), and sleep hygiene (poor emotion at bedtime, unstable sleep schedule). The clinical significance of the findings lies in the emphasis of comprehensive screening of sleep in the predicting, diagnosis, nursing, and intervention of adolescents' mental health problems.

  12. Cytokines in sleep regulation.

    Science.gov (United States)

    Krueger, J M; Takahashi, S; Kapás, L; Bredow, S; Roky, R; Fang, J; Floyd, R; Renegar, K B; Guha-Thakurta, N; Novitsky, S

    1995-01-01

    The central thesis of this essay is that the cytokine network in brain is a key element in the humoral regulation of sleep responses to infection and in the physiological regulation of sleep. We hypothesize that many cytokines, their cellular receptors, soluble receptors, and endogenous antagonists are involved in physiological sleep regulation. The expressions of some cytokines are greatly amplified by microbial challenge. This excess cytokine production during infection induces sleep responses. The excessive sleep and wakefulness that occur at different times during the course of the infectious process results from dynamic changes in various cytokines that occur during the host's response to infectious challenge. Removal of any one somnogenic cytokine inhibits normal sleep, alters the cytokine network by changing the cytokine mix, but does not completely disrupt sleep due to the redundant nature of the cytokine network. The cytokine network operates in a paracrine/autocrine fashion and is responsive to neuronal use. Finally, cytokines elicit their somnogenic actions via endocrine and neurotransmitter systems as well as having direct effects neurons and glia. Evidence in support of these postulates is reviewed in this essay.

  13. Rhinitis and sleep.

    Science.gov (United States)

    Lunn, Michael; Craig, Timothy

    2011-10-01

    Allergic rhinitis is a very prevalent disease in developed nations and has been increasing throughout the world. Nasal congestion is one of the most common and bothersome symptoms of rhinitis in both children and adults. Congestion is associated with sleep-disordered breathing and is thought to be a key cause of sleep impairment in rhinitis. The end result is decrease in quality of life and productivity and increased daytime sleepiness. Treatment with intranasal corticosteroids has been shown to reduce nasal congestion. Data on sleep-related endpoints from clinical trials of intranasal corticosteroids indicate that this reduction is associated with improved sleep, reduced daytime fatigue, and improved quality of life. Other therapies, such as montelukast, also have a positive influence on congestion and sleep, while still other therapies for rhinitis do not affect either symptom. This review examines nasal congestion and the associated sleep impairment with allergic rhinitis. It explores the adverse effects of disturbed sleep on patients' quality of life and how these disturbances can be reduced by therapies that address nasal congestion. Copyright © 2010 Elsevier Ltd. All rights reserved.

  14. Sleep disorders in children.

    Science.gov (United States)

    Hoban, Timothy F

    2013-02-01

    The purpose of this review is to examine how sleep disorders in children are affected by age and comorbid medical influences, and to discuss current understanding of how the clinical manifestations, pathophysiology, and treatment of common childhood sleep disorders differ from those of the adult population. Recently established age-specific norms are required for accurate interpretation of polysomnograms and multiple sleep latency tests in children. Sleep disorders such as insomnia, obstructive sleep apnea, and excessive daytime somnolence are common in both children and adults, but the clinical manifestations and underlying pathophysiology of these disorders vary substantially with age. For example, the bedtime struggles of a temperamental toddler are associated with different symptoms and causative factors compared to psychophysiologic insomnia affecting a middle-aged person. Similarly, a 6-year-old child with obstructive sleep apnea is more likely to exhibit daytime inattention and hyperactivity as a referable daytime symptom than the clear-cut lethargy or sleepiness that most affected adults experience. This review will examine how insomnia, excessive sleepiness, and obstructive sleep apnea differ in children compared to adults.

  15. Insomnia and sleep misperception.

    Science.gov (United States)

    Bastien, C H; Ceklic, T; St-Hilaire, P; Desmarais, F; Pérusse, A D; Lefrançois, J; Pedneault-Drolet, M

    2014-10-01

    Sleep misperception is often observed in insomnia individuals (INS). The extent of misperception varies between different types of INS. The following paper comprised sections which will be aimed at studying the sleep EEG and compares it to subjective reports of sleep in individuals suffering from either psychophysiological insomnia or paradoxical insomnia and good sleeper controls. The EEG can be studied without any intervention (thus using the raw data) via either PSG or fine quantitative EEG analyses (power spectral analysis [PSA]), identifying EEG patterns as in the case of cyclic alternating patterns (CAPs) or by decorticating the EEG while scoring the different transient or phasic events (K-Complexes or sleep spindles). One can also act on the on-going EEG by delivering stimuli so to study their impact on cortical measures as in the case of event-related potential studies (ERPs). From the paucity of studies available using these different techniques, a general conclusion can be reached: sleep misperception is not an easy phenomenon to quantify and its clinical value is not well recognized. Still, while none of the techniques or EEG measures defined in the paper is available and/or recommended to diagnose insomnia, ERPs might be the most indicated technique to study hyperarousal and sleep quality in different types of INS. More research shall also be dedicated to EEG patterns and transient phasic events as these EEG scoring techniques can offer a unique insight of sleep misperception. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  16. Consequences of sleep deprivation.

    Science.gov (United States)

    Orzeł-Gryglewska, Jolanta

    2010-01-01

    This paper presents the history of research and the results of recent studies on the effects of sleep deprivation in animals and humans. Humans can bear several days of continuous sleeplessness, experiencing deterioration in wellbeing and effectiveness; however, also a shorter reduction in the sleep time may lead to deteriorated functioning. Sleeplessness accounts for impaired perception, difficulties in keeping concentration, vision disturbances, slower reactions, as well as the appearance of microepisodes of sleep during wakefulness which lead to lower capabilities and efficiency of task performance and to increased number of errors. Sleep deprivation results in poor memorizing, schematic thinking, which yields wrong decisions, and emotional disturbances such as deteriorated interpersonal responses and increased aggressiveness. The symptoms are accompanied by brain tissue hypometabolism, particularly in the thalamus, prefrontal, frontal and occipital cortex and motor speech centres. Sleep deficiency intensifies muscle tonus and coexisting tremor, speech performance becomes monotonous and unclear, and sensitivity to pain is higher. Sleeplessness also relates to the changes in the immune response and the pattern of hormonal secretion, of the growth hormone in particular. The risk of obesity, diabetes and cardiovascular disease increases. The impairment of performance which is caused by 20-25 hours of sleeplessness is comparable to that after ethanol intoxication at the level of 0.10% blood alcohol concentration. The consequences of chronic sleep reduction or a shallow sleep repeated for several days tend to accumulate and resemble the effects of acute sleep deprivation lasting several dozen hours. At work, such effects hinder proper performance of many essential tasks and in extreme situations (machine operation or vehicle driving), sleep loss may be hazardous to the worker and his/her environment.

  17. Sleep Quality Among Psychiatry Residents.

    Science.gov (United States)

    Carvalho Aguiar Melo, Matias; das Chagas Medeiros, Francisco; Meireles Sales de Bruin, Veralice; Pinheiro Santana, José Abraão; Bastos Lima, Alexandre; De Francesco Daher, Elizabeth

    2016-01-01

    Medical residency programs are traditionally known for long working hours, which can be associated with a poor quality of sleep and daytime sleepiness. However, few studies have focused on this theme. Our objective was to investigate sleep quality, daytime sleepiness, and their relation with anxiety, social phobia, and depressive symptoms. This cross-sectional observational study involved 59 psychiatry residents. The Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) were used to measure the quality of sleep and excessive daytime sleepiness ([EDS] and ESS > 10), respectively. Among the 59 psychiatry residents, 59.3% had poor sleep quality (PSQI > 5) and 28.8% had EDS. Poor sleep quality was associated with higher EDS (P = 0.03) and the year of residency program (P = 0.03). Only 20% of residents with poor sleep had consulted at least once for sleep problems; 54.2% had used medications for sleep; and 16.9% were using medications at the time of interview. Only 30% obtained medication during medical consultations. Poor sleep was associated with irregular sleep hours (P = 0.001) and long periods lying down without sleep (P = 0.03). Poor sleep quality was also associated with high scores of anxiety symptoms (P Psychiatry residents frequently have poor sleep quality and EDS. Considering that sleep disorders can affect quality of life, predispose to metabolic syndrome, and be associated with worse performance at work, attention to this clinical problem is needed. © The Author(s) 2016.

  18. Relationship of sleep hygiene awareness, sleep hygiene practices, and sleep quality in university students.

    Science.gov (United States)

    Brown, Franklin C; Buboltz, Walter C; Soper, Barlow

    2002-01-01

    College students are known for their variable sleep schedules. Such schedules, along with other common student practices (e.g., alcohol and caffeine consumption), are associated with poor sleep hygiene. Researchers have demonstrated in clinical populations that improving sleep hygiene knowledge and practices is an effective treatment for insomnia. However, researchers who have examined relationships between sleep hygiene and practices in nonclinical samples and overall sleep quality have produced inconsistent findings, perhaps because of questionable measures. In this study, the authors used psychometrically sound instruments to examine these variables and to counter the shortcomings in previous investigations. Their findings suggest that knowledge of sleep hygiene is related to sleep practices, which, in turn, is related to overall sleep quality. The data from their regression modeling indicated that variable sleep schedules, going to bed thirsty, environmental noise, and worrying while falling asleep contribute to poor sleep quality.

  19. Comparative biochemical and pathological changes in some laboratory animals experimentally infected with Trypanosoma brucei and their responses to diminazene diaceturate (Veriben® therapy

    Directory of Open Access Journals (Sweden)

    Amina Ibrahim

    2015-12-01

    Full Text Available Objective: To compare the biochemical and pathological changes of Trypanosoma brucei brucei infected mice, rats and rabbits, and study the chemotherapeutic effects according to standard criteria. Methods: A total of 20 Balb/c Albino mice, 20 Wister Albino rats and 20 New Zealand rabbits, all adults and of both sexes were used in the study. Each rodent group was divided into four groups (A, B, C and D of five animals each. Animals in Groups A and C were individually infected with 0.5 mL of blood from donor rats containing 1.5 ××106 Trypanasoma brucei brucei, while Groups B and D remained uninfected. The animals were later treated like this: Group A (infected and untreated control, Group B (uninfected and untreated control, Group C (infected and treated and Group D (uninfected and treated. The treatment was administered on Day 12 after infection. Results: The prepatent period for mice and rats was 4 days while that for rabbits was 8 days. There was a significant (P < 0.05 increase in levels of liver enzymes and serum metabolites which were more marked among the mice and rats than rabbits. These changes were modulated to their preinfection values in the infected treated animals. At necropsy, all animals showed splenomegaly, hepatomegaly and nephritis. However, cardiomegaly was exclusive to the rabbits. Histopathologically, degenerative changes were observed in both the liver and kidneys which were more severe among mice and rats and moderate in rabbits. Spleen of mice showed giant macrophages, while that of the rats showed epithelioid giant cells. However, spleen of rabbits showed haemosiderosis and eosinophilic infiltrations. Hydrophobic degeneration, necrosis and mononuclear cell infiltrations in the myocardium were observed only among rabbits. Conclusions: Diminazene diaceturate was able to ameliorate the various biochemical and pathological changes which were suggestive of severe liver and kidney dysfunctions with greater intensity occurring

  20. Sleep and Diabetes

    Directory of Open Access Journals (Sweden)

    Swetha Bopparaju

    2010-01-01

    Full Text Available Sleep apnea is clinically recognized as a heterogeneous group of disorders characterized by recurrent apnea and/or hypopnea. Its prevalence ranges from 4% to 24%. It has been implicated as an independent risk factor for several conditions such as hypertension, stroke, arrhythmia, and myocardial infarction. Recently data has been emerging which suggests an independent association of obstructive sleep apnea with several components of the metabolic syndrome, particularly insulin resistance and abnormalities in lipid metabolism. We hereby review the salient features of the association between sleep and diabetes.

  1. Unraveling the Neurobiology of Sleep and Sleep Disorders Using Drosophila.

    Science.gov (United States)

    Chakravarti, L; Moscato, E H; Kayser, M S

    2017-01-01

    Sleep disorders in humans are increasingly appreciated to be not only widespread but also detrimental to multiple facets of physical and mental health. Recent work has begun to shed light on the mechanistic basis of sleep disorders like insomnia, restless legs syndrome, narcolepsy, and a host of others, but a more detailed genetic and molecular understanding of how sleep goes awry is lacking. Over the past 15 years, studies in Drosophila have yielded new insights into basic questions regarding sleep function and regulation. More recently, powerful genetic approaches in the fly have been applied toward studying primary human sleep disorders and other disease states associated with dysregulated sleep. In this review, we discuss the contribution of Drosophila to the landscape of sleep biology, examining not only fundamental advances in sleep neurobiology but also how flies have begun to inform pathological sleep states in humans. © 2017 Elsevier Inc. All rights reserved.

  2. Interaction between the flagellar pocket collar and the hook complex via a novel microtubule-binding protein in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Anna Albisetti

    2017-11-01

    Full Text Available Trypanosoma brucei belongs to a group of unicellular, flagellated parasites that are responsible for human African trypanosomiasis. An essential aspect of parasite pathogenicity is cytoskeleton remodelling, which occurs during the life cycle of the parasite and is accompanied by major changes in morphology and organelle positioning. The flagellum originates from the basal bodies and exits the cell body through the flagellar pocket (FP but remains attached to the cell body via the flagellum attachment zone (FAZ. The FP is an invagination of the pellicular membrane and is the sole site for endo- and exocytosis. The FAZ is a large complex of cytoskeletal proteins, plus an intracellular set of four specialised microtubules (MtQ that elongate from the basal bodies to the anterior end of the cell. At the distal end of the FP, an essential, intracellular, cytoskeletal structure called the flagellar pocket collar (FPC circumvents the flagellum. Overlapping the FPC is the hook complex (HC (a sub-structure of the previously named bilobe that is also essential and is thought to be involved in protein FP entry. BILBO1 is the only functionally characterised FPC protein and is necessary for FPC and FP biogenesis. Here, we used a combination of in vitro and in vivo approaches to identify and characterize a new BILBO1 partner protein-FPC4. We demonstrate that FPC4 localises to the FPC, the HC, and possibly to a proximal portion of the MtQ. We found that the C-terminal domain of FPC4 interacts with the BILBO1 N-terminal domain, and we identified the key amino acids required for this interaction. Interestingly, the FPC4 N-terminal domain was found to bind microtubules. Over-expression studies highlight the role of FPC4 in its association with the FPC, HC and FPC segregation. Our data suggest a tripartite association between the FPC, the HC and the MtQ.

  3. Crystal Structures of Trypanosoma brucei Sterol 14[alpha]-Demethylase and Implications for Selective Treatment of Human Infections

    Energy Technology Data Exchange (ETDEWEB)

    Lepesheva, Galina I.; Park, Hee-Won; Hargrove, Tatiana Y.; Vanhollebeke, Benoit; Wawrzak, Zdzislaw; Harp, Joel M.; Sundaramoorthy, Munirathinam; Nes, W. David; Pays, Etienne; Chaudhuri, Minu; Villalta, Fernando; Waterman, Michael R. (ULdB); (Vanderbilt); (TTU); (Toronto); (NWU); (Meharry)

    2010-01-25

    Sterol 14{alpha}-demethylase (14DM, the CYP51 family of cytochrome P450) is an essential enzyme in sterol biosynthesis in eukaryotes. It serves as a major drug target for fungal diseases and can potentially become a target for treatment of human infections with protozoa. Here we present 1.9 {angstrom} resolution crystal structures of 14DM from the protozoan pathogen Trypanosoma brucei, ligand-free and complexed with a strong chemically selected inhibitor N-1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethyl-4-(5-phenyl-1,3,4-oxadi-azol-2-yl)benzamide that we previously found to produce potent antiparasitic effects in Trypanosomatidae. This is the first structure of a eukaryotic microsomal 14DM that acts on sterol biosynthesis, and it differs profoundly from that of the water-soluble CYP51 family member from Mycobacterium tuberculosis, both in organization of the active site cavity and in the substrate access channel location. Inhibitor binding does not cause large scale conformational rearrangements, yet induces unanticipated local alterations in the active site, including formation of a hydrogen bond network that connects, via the inhibitor amide group fragment, two remote functionally essential protein segments and alters the heme environment. The inhibitor binding mode provides a possible explanation for both its functionally irreversible effect on the enzyme activity and its selectivity toward the 14DM from human pathogens versus the human 14DM ortholog. The structures shed new light on 14DM functional conservation and open an excellent opportunity for directed design of novel antiparasitic drugs.

  4. Sustained Sleep Fragmentation Induces Sleep Homeostasis in Mice

    Science.gov (United States)

    Baud, Maxime O.; Magistretti, Pierre J.; Petit, Jean-Marie

    2015-01-01

    Study Objectives: Sleep fragmentation (SF) is an integral feature of sleep apnea and other prevalent sleep disorders. Although the effect of repetitive arousals on cognitive performance is well documented, the effects of long-term SF on electroencephalography (EEG) and molecular markers of sleep homeostasis remain poorly investigated. To address this question, we developed a mouse model of chronic SF and characterized its effect on EEG spectral frequencies and the expression of genes previously linked to sleep homeostasis including clock genes, heat shock proteins, and plasticity-related genes. Design: N/A. Setting: Animal sleep research laboratory. Participants : Sixty-six C57BL6/J adult mice. Interventions: Instrumental sleep disruption at a rate of 60/h during 14 days Measurements and Results: Locomotor activity and EEG were recorded during 14 days of SF followed by recovery for 2 days. Despite a dramatic number of arousals and decreased sleep bout duration, SF minimally reduced total quantity of sleep and did not significantly alter its circadian distribution. Spectral analysis during SF revealed a homeostatic drive for slow wave activity (SWA; 1–4 Hz) and other frequencies as well (4–40 Hz). Recordings during recovery revealed slow wave sleep consolidation and a transient rebound in SWA, and paradoxical sleep duration. The expression of selected genes was not induced following chronic SF. Conclusions: Chronic sleep fragmentation (SF) increased sleep pressure confirming that altered quality with preserved quantity triggers core sleep homeostasis mechanisms. However, it did not induce the expression of genes induced by sleep loss, suggesting that these molecular pathways are not sustainably activated in chronic diseases involving SF. Citation: Baud MO, Magistretti PJ, Petit JM. Sustained sleep fragmentation induces sleep homeostasis in mice. SLEEP 2015;38(4):567–579. PMID:25325477

  5. Sleep Habits and Sleep Problems in Healthy Preschoolers.

    Science.gov (United States)

    Murthy, C L Srinivasa; Bharti, Bhavneet; Malhi, Prahbhjot; Khadwal, Alka

    2015-07-01

    To describe the sleep patterns and problems in children aged between 12 and 36 mo of age. This cross sectional survey was collected over a span of 1 y in Advanced Pediatric Centre, PGIMER, Chandigarh and crèches of Chandigarh. Children in the age group of 12 to 36 mo were included in study. Children with chronic illness, developmental delay, seizure disorder and lack of consent were excluded. A total of 368 children were enrolled. Main outcome measures were sleep duration over 1 to 3 y of life; sleep behavior at onset, during and waking of sleep and parent reported sleep problems and their predictors. The average duration of sleep was 12.5 h (S.D = 1.9). The mean total sleep duration and mean day time sleep duration decreased, while mean night time sleep increased as the age advanced from 12 to 36 mo. Following were the frequency of sleep habits seen in the index study; bed time routine was seen only in 68(18.5 %), a regular bed time ritual was seen in 281(76.4 %), 329(89.4 %) children frequently required 0-20 min time to fall asleep, 11(3 %) parents used sleep inducing drugs. Night waking (1 to 3 times a night) was seen in 297(80.7 %) and its frequency declined with age. Parent reported sleep problems were seen in 12.8 % (47/368). Lack of co-sleeping and night waking were considered as strongest predictors of parent reported sleep problems. Toddlers' sleep duration, night waking behavior, and day time naps decrease as the age progress while night time sleep duration increases with age. Lack of co-sleeping and night waking are considered as strongest predictors of parent reported sleep problems.

  6. Guide to Understanding Your Sleep Study

    Science.gov (United States)

    ... efficiency. People who have significant difficulties in either initiating or maintaining sleep have diminished sleep efficiency, which ... repeatedly between Non-REM and REM sleep. The structure of these cycles–poetically known as “sleep architecture”– ...

  7. Functions and Mechanisms of Sleep

    Directory of Open Access Journals (Sweden)

    Mark R. Zielinski

    2016-04-01

    Full Text Available Sleep is a complex physiological process that is regulated globally, regionally, and locally by both cellular and molecular mechanisms. It occurs to some extent in all animals, although sleep expression in lower animals may be co-extensive with rest. Sleep regulation plays an intrinsic part in many behavioral and physiological functions. Currently, all researchers agree there is no single physiological role sleep serves. Nevertheless, it is quite evident that sleep is essential for many vital functions including development, energy conservation, brain waste clearance, modulation of immune responses, cognition, performance, vigilance, disease, and psychological state. This review details the physiological processes involved in sleep regulation and the possible functions that sleep may serve. This description of the brain circuitry, cell types, and molecules involved in sleep regulation is intended to further the reader’s understanding of the functions of sleep.

  8. Impaired sleep and allostatic load

    DEFF Research Database (Denmark)

    Clark, Alice Jessie; Dich, Nadya; Lange, Theis

    2014-01-01

    Objective: Understanding the mechanisms linking sleep impairment to morbidity and mortality is important for future prevention, but these mechanisms are far from elucidated. We aimed to determine the relation between impaired sleep, both in terms of duration and disturbed sleep, and allostatic load...... Biobank with comprehensive information on sleep duration, disturbed sleep, objective measures of an extensive range of biological risk markers, and physical conditions. Results: Long sleep (mean difference 0.23; 95% confidence interval, 0.13, 0.32) and disturbed sleep (0.14; 0.06, 0.22) were associated...... with higher AL as well as with high-risk levels of risk markers from the anthropometric, metabolic, and immune system. Sub-analyses suggested that the association between disturbed sleep and AL might be explained by underlying disorders. Whereas there was no association between short sleep and AL...

  9. Social Relationships and Sleep Quality.

    Science.gov (United States)

    Kent, Robert G; Uchino, Bert N; Cribbet, Matthew R; Bowen, Kimberly; Smith, Timothy W

    2015-12-01

    The quality of social relationships and social support appears to be associated with physical health outcomes and sleep quality. Almost all previous research in this area focuses on positive aspects of relationships. The present study thus intended to examine the links between supportive, aversive, ambivalent, and indifferent network ties and sleep quality. Relationship data, Pittsburgh Sleep Quality Index (PSQI)-assessed sleep quality, and depression were examined in 175 middle-aged and older adults. Consistent with hypotheses, supportive ties were positively related to sleep quality, while aversive ties predicted worse sleep quality, associations that were primarily seen for close relationships. Ambivalent and indifferent ties were not significant predictors of sleep quality. Importantly, depression was found to mediate the link between relationship quality and sleep quality. These data suggest the more specific types of social relationships that may be linked to poor sleep quality and that depression appears to underlie these associations.

  10. Sleep Apnea Detection

    Science.gov (United States)

    ... to monitor breathing, oxygenation, and brain waves (electroencephalogram; EEG). The results of the study will show whether your child suffers from sleep apnea. Other specialists, such as pediatric pulmonologists , otolaryngologists , ...

  11. Aging changes in sleep

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/004018.htm Aging changes in sleep To use the sharing features ... to function) or addiction (compulsive use despite adverse consequences). Some of these drugs build up in your ...

  12. Obstructive Sleep Apnea

    Science.gov (United States)

    ... pauses in your breathing during sleep Excessive daytime drowsiness, which may cause you to fall asleep while you're working, watching television or even driving a vehicle Many people may not think of ...

  13. Polysomnography (Sleep Study)

    Science.gov (United States)

    ... this stage, your brain waves, as recorded by electroencephalography (EEG), slow down considerably. Your eyes don't move ... level Body position Limb movement Snoring and other noise you may make as you sleep All of ...

  14. National Sleep Foundation

    Science.gov (United States)

    ... Latvian Lithuanian Macedonian Malay Maltese Norwegian Persian Polish Portuguese Romanian Russian Serbian Slovak Slovenian Spanish Swahili Swedish ... Relieve Ear Pressure While Traveling for Better Sleep Learn how to keep your ears happy so you ...

  15. Safe Sleep for Babies

    Science.gov (United States)

    ... serve mothers and babies to deliver culturally appropriate messaging about safe sleep for babies. Monitoring and evaluating ... RSS ABOUT About CDC Jobs Funding LEGAL Policies Privacy FOIA No Fear Act OIG 1600 Clifton Road ...

  16. [Sleep related movement disorders].

    Science.gov (United States)

    Suzuki, Keisuke; Miyamoto, Masayuki; Miyamoto, Tomoyuki; Hirata, Koichi

    2015-06-01

    Sleep related movement disorders (SRMD) are characterized by simple, stereotyped movements occur during sleep, with the exception of restless legs syndrome (RLS). RLS has the following essential features; an urge to move the legs usually accompanied by uncomfortable sensation in the legs, improvement of symptoms after movement (non-stereotypical movements, such as walking and stretching, to reduce symptoms), and symptoms occur or worsen during periods of rest and in the evening and night. However, RLS is closely associated with periodic limb movement, which shows typical stererotyped limb movements. In the International Classification of Sleep Disorders, 3rd edition, sleep disturbances or daytime symptoms are prerequiste for a diagnosis of SRMD. We here review diagnosis and treatment of SRMD.

  17. Sleep State Switching

    National Research Council Canada - National Science Library

    Saper, Clifford B; Fuller, Patrick M; Pedersen, Nigel P; Lu, Jun; Scammell, Thomas E

    2010-01-01

    We take for granted the ability to fall asleep or to snap out of sleep into wakefulness, but these changes in behavioral state require specific switching mechanisms in the brain that allow well-defined state transitions...

  18. Why Is Sleep Important

    Science.gov (United States)

    ... Drivers aren't the only ones affected by sleep deficiency. It can affect people in all lines of work, including health care workers, pilots, students, lawyers, mechanics, and assembly line workers. As a ...

  19. Sleep after laparoscopic cholecystectomy

    DEFF Research Database (Denmark)

    Rosenberg-Adamsen, S; Skarbye, M; Wildschiødtz, G

    1996-01-01

    The sleep pattern and oxygenation of 10 patients undergoing laparoscopic cholecystectomy were studied on the night before operation and the first night after operation. Operations were performed during general anaesthesia and postoperative analgesia was achieved without the administration...... of opioids. There were no significant changes in the total time awake or the number of arousals on the postoperative night compared with the night before operation. During the postoperative night, we found a decrease (P = 0.02) in slow wave sleep (SWS) with a corresponding increase in stage 2 sleep (P = 0.......01). SWS was absent in four of the patients after operation, whereas in six patients it was within the normal range (5-20% of the night). The proportion of rapid eye movement (REM) sleep was not significantly changed after operation. There were no changes in arterial oxygen saturation on the postoperative...

  20. Sleep and Your Preschooler

    Science.gov (United States)

    ... develop good, consistent habits for getting to sleep. Benefits of a Bedtime Routine A bedtime routine is ... consistent playtimes and mealtimes. Avoid stimulants, such as caffeine, near bedtime. Make the bedroom quiet, cozy, and ...

  1. Sleep Deprivation and Deficiency

    Science.gov (United States)

    ... adults report falling asleep during the day without meaning to at least once a month. Also, an ... Sleep deficiency also has been linked to depression, suicide, and risk-taking behavior. Children and teens who ...

  2. Exercise Effects on Sleep Physiology

    Directory of Open Access Journals (Sweden)

    Sunao eUchida

    2012-04-01

    Full Text Available This mini-review focuses on the effects of exercise on sleep. In its early days, sleep research largely focused on central nervous system (CNS physiology using standardized tabulations of several sleep-specific landmark electroencephalogram (EEG waveforms. Though coarse, this method has enabled the observation and inspection of numerous uninterrupted sleep phenomena. Thus, research on the effects of exercise on sleep began, in the 1960’s, with a focus primarily on sleep EEG (CNS sleep changes. Those early studies found only small effects of exercise on sleep. More recent sleep research has explored not only CNS functioning, but somatic physiology as well. As physical exercise mostly affects somatic functions, endocrine and autonomic nervous system (ANS changes that occur during sleep should be affected by daytime exercise. Since endocrinological, metabolic and autonomic changes can be measured during sleep, it should be possible to assess exercise effects on somatic physiology in addition to CNS sleep quality, building from standard polysomnographic (PSG techniques. Incorporating measures of somatic physiology in the quantitative assessment of sleep could further our understanding of sleep's function as an auto-regulatory, global phenomenon.

  3. Sleep and psychoneuroimmunology.

    Science.gov (United States)

    Opp, Mark R

    2009-05-01

    The brain uses a variety of mechanisms to survey the immune system constantly. Responses of the immune system to invading pathogens are detected by the central nervous system, which responds by orchestrating complex changes in behavior and physiology. Sleep is one of the behaviors altered in response to immune challenge. The role of cytokines as mediators of responses to infectious challenge and regulators and modulators of sleep is the focus of this article.

  4. SLEEP APNOEA!!! : SNORING & BEYOND

    Indian Academy of Sciences (India)

    SLEEP APNOEA!!! : SNORING & BEYOND · Slide 2 · Snoring · Introduction · Identifiable causes of hypertension · Crucial areas for Snoring & Obstructive Sleep Apnea · Slide 7 · Slide 8 · Slide 9 · Slide 10 · Slide 11 · Slide 12 · Slide 13 · Slide 14 · Slide 15 · Slide 16 · Epidemiology (contd.) Slide 18 · Am I at risk??? Slide 20.

  5. Autism and sleep disorders

    OpenAIRE

    Devnani, Preeti A.; Hegde, Anaita U.

    2015-01-01

    “Autism Spectrum Disorders” (ASDs) are neurodevelopment disorders and are characterized by persistent impairments in reciprocal social interaction and communication. Sleep problems in ASD, are a prominent feature that have an impact on social interaction, day to day life, academic achievement, and have been correlated with increased maternal stress and parental sleep disruption. Polysomnography studies of ASD children showed most of their abnormalities related to rapid eye movement (REM) slee...

  6. Alcohol and the sleeping brain.

    Science.gov (United States)

    Colrain, Ian M; Nicholas, Christian L; Baker, Fiona C

    2014-01-01

    Alcohol acts as a sedative that interacts with several neurotransmitter systems important in the regulation of sleep. Acute administration of large amounts of alcohol prior to sleep leads to decreased sleep-onset latency and changes in sleep architecture early in the night, when blood alcohol levels are high, with subsequent disrupted, poor-quality sleep later in the night. Alcohol abuse and dependence are associated with chronic sleep disturbance, lower slow-wave sleep, and more rapid-eye-movement sleep than normal, that last long into periods of abstinence and may play a role in relapse. This chapter outlines the evidence for acute and chronic alcohol effects on sleep architecture and sleep electroencephalogram, evidence for tolerance with repeated administration, and possible underlying neurochemical mechanisms for alcohol's effects on sleep. Also discussed are sex differences as well as effects of alcohol on sleep homeostasis and circadian regulation. Evidence for the role of sleep disruption as a risk factor for developing alcohol dependence is discussed in the context of research conducted in adolescents. The utility of sleep-evoked potentials in the assessment of the effects of alcoholism on sleep and the brain and in abstinence-mediated recovery is also outlined. The chapter concludes with a series of questions that need to be answered to determine the role of sleep and sleep disturbance in the development and maintenance of problem drinking and the potential beneficial effects of the treatment of sleep disorders for maintenance of abstinence in alcoholism. © 2014 Elsevier B.V. All rights reserved.

  7. Characterizing Sleep Issues Using Twitter.

    Science.gov (United States)

    McIver, David J; Hawkins, Jared B; Chunara, Rumi; Chatterjee, Arnaub K; Bhandari, Aman; Fitzgerald, Timothy P; Jain, Sachin H; Brownstein, John S

    2015-06-08

    Sleep issues such as insomnia affect over 50 million Americans and can lead to serious health problems, including depression and obesity, and can increase risk of injury. Social media platforms such as Twitter offer exciting potential for their use in studying and identifying both diseases and social phenomenon. Our aim was to determine whether social media can be used as a method to conduct research focusing on sleep issues. Twitter posts were collected and curated to determine whether a user exhibited signs of sleep issues based on the presence of several keywords in tweets such as insomnia, "can't sleep", Ambien, and others. Users whose tweets contain any of the keywords were designated as having self-identified sleep issues (sleep group). Users who did not have self-identified sleep issues (non-sleep group) were selected from tweets that did not contain pre-defined words or phrases used as a proxy for sleep issues. User data such as number of tweets, friends, followers, and location were collected, as well as the time and date of tweets. Additionally, the sentiment of each tweet and average sentiment of each user were determined to investigate differences between non-sleep and sleep groups. It was found that sleep group users were significantly less active on Twitter (P=.04), had fewer friends (Puser's account has been active. Sleep group users were more active during typical sleeping hours than others, which may suggest they were having difficulty sleeping. Sleep group users also had significantly lower sentiment in their tweets (P<.001), indicating a possible relationship between sleep and pyschosocial issues. We have demonstrated a novel method for studying sleep issues that allows for fast, cost-effective, and customizable data to be gathered.

  8. Can non-REM sleep be depressogenic?

    OpenAIRE

    Beersma, Domien G. M.; Hoofdakker, Rutger H. van den

    1992-01-01

    Sleep and mood are clearly interrelated in major depression, as shown by the antidepressive effects of various experiments, such as total sleep deprivation, partial sleep deprivation, REM sleep deprivation, and temporal shifts of the sleep period. The prevailing hypotheses explaining these effects concern the antidepressant potency of the suppression of either REM sleep or non-REM sleep. This issue is discussed in the light of present knowledge of the kinetics of non-REM sleep intensity, REM ...

  9. Obstructive sleep apnea

    Directory of Open Access Journals (Sweden)

    Steven D. Brass

    2011-11-01

    Full Text Available Obstructive sleep apnea (OSA affects millions of Americans and is estimated to be as prevalent as asthma and diabetes. Given the fact that obesity is a major risk factor for OSA, and given the current global rise in obesity, the prevalence of OSA will increase in the future. Individuals with sleep apnea are often unaware of their sleep disorder. It is usually first recognized as a problem by family members who witness the apneic episodes or is suspected by their primary care doctor because of the individual’s risk factors and symptoms. The vast majority remain undiagnosed and untreated, despite the fact that this serious disorder can have significant consequences. Individuals with untreated OSA can stop breathing hundreds of times a night during their sleep. These apneic events can lead to fragmented sleep that is of poor quality, as the brain arouses briefly in order for the body to resume breathing. Untreated, sleep apnea can have dire health consequences and can increase the risk of hypertension, diabetes, heart disease, and heart failure. OSA management has also become important in a number of comorbid neurological conditions, including epilepsy, stroke, multiple sclerosis, and headache. Diagnosis typically involves use of screening questionnaires, physical exam, and an overnight polysomnography or a portable home study. Treatment options include changes in lifestyle, positive airway pressure, surgery, and dental appliances.

  10. Sleep Paralysis and Hallucinosis

    Directory of Open Access Journals (Sweden)

    Gregory Stores

    1998-01-01

    Full Text Available Background: Sleep paralysis is one of the many conditions of which visual hallucinations can be a part but has received relatively little attention. It can be associated with other dramatic symptoms of a psychotic nature likely to cause diagnostic uncertainty. Methods and results: These points are illustrated by the case of a young man with a severe bipolar affective disorder who independently developed terrifying visual, auditory and somatic hallucinatory episodes at sleep onset, associated with a sense of evil influence and presence. The episodes were not obviously related to his psychiatric disorder. Past diagnoses included nightmares and night terrors. Review provided no convincing evidence of various other sleep disorders nor physical conditions in which hallucinatory experiences can occur. A diagnosis of predormital isolated sleep paralysis was made and appropriate treatment recommended. Conclusions: Sleep paralysis, common in the general population, can be associated with dramatic auxiliary symptoms suggestive of a psychotic state. Less common forms are either part of the narcolepsy syndrome or (rarely they are familial in type. Interestingly, sleep paralysis (especially breathing difficulty features prominently in the folklore of various countries.

  11. Sleep apnea headaches

    Directory of Open Access Journals (Sweden)

    Reza Boostani

    2016-12-01

    Full Text Available Obstructive sleep apnea syndrome (OSAS is a common disorder characterized by recurrent apnea during sleep. Nocturnal laboratory-based polysomnography (PSG is the gold standard test for diagnosis of OSA. The sufferers may complain from daytime sleepiness, snoring or occasional headaches. Serious consequences such as cardiovascular complications, stroke or symptoms of depression may complicate the syndrome. Headache prevalence due to sleep apnea is estimated 1%-2% in general population and affects 2%-8% of middle age population. Morning headache is more common in the OSAS patients. OSAS patients present with various characteristics of morning headache. Treatment with continuous positive airway pressure usually reduces headache. The pathophysiologic background for a relation between obstructive sleep apnea and morning headache is multifactorial. Some theories have been proposed for OSAS-related headaches such as changing oxygen saturation during sleep, cerebral vasodilation and increased intracranial pressure due to cerebral vasodilation, sleep disruption and depression but the definite cause of headaches in OSAS patients is not yet clear.

  12. Sleep Duration, Restfulness, and Screens in the Sleep Environment

    Science.gov (United States)

    Davison, Kirsten K.; Franckle, Rebecca L.; Ganter, Claudia; Gortmaker, Steven L.; Smith, Lauren; Land, Thomas; Taveras, Elsie M.

    2015-01-01

    BACKGROUND AND OBJECTIVE: Associations of inadequate sleep with numerous health outcomes among youth necessitate identifying its modifiable determinants. Television (TV) has been associated with sleep curtailment, but little is known about small screens (eg, smartphones), which can be used in bed and emit notifications. Therefore, we examined associations of different screens in sleep environments with sleep duration and perceived insufficient rest or sleep. METHODS: Participants included 2048 fourth- and seventh-graders participating in the Massachusetts Childhood Obesity Research Demonstration Study in 2012 to 2013. Using linear and log binomial regression, we examined cross-sectional associations of small screens and TVs in sleep environments and screen time with weekday sleep duration and perceived insufficient rest or sleep in the past week. RESULTS: Children who slept near a small screen (compared with never) reported 20.6 fewer minutes of sleep (95% confidence interval [CI], −29.7 to −11.4) and had a higher prevalence of perceived insufficient rest or sleep (prevalence ratio, 1.39; 95% CI, 1.21 to 1.60). Children who slept in a room with a TV (compared with no TV) reported 18.0 fewer minutes of sleep (95% CI, −27.9 to −8.1). TV or DVD viewing and video or computer game playing were associated with both sleep outcomes (P < .01). Some associations were stronger among Hispanic, non-Hispanic black, and older children (P < .05 for heterogeneity). CONCLUSIONS: Sleeping near a small screen, sleeping with a TV in the room, and more screen time were associated with shorter sleep durations. Presence of a small screen, but not a TV, in the sleep environment and screen time were associated with perceived insufficient rest or sleep. These findings caution against unrestricted screen access in children’s bedrooms. PMID:25560435

  13. Obstructive sleep apnea alters sleep stage transition dynamics.

    Directory of Open Access Journals (Sweden)

    Matt T Bianchi

    2010-06-01

    Full Text Available Enhanced characterization of sleep architecture, compared with routine polysomnographic metrics such as stage percentages and sleep efficiency, may improve the predictive phenotyping of fragmented sleep. One approach involves using stage transition analysis to characterize sleep continuity.We analyzed hypnograms from Sleep Heart Health Study (SHHS participants using the following stage designations: wake after sleep onset (WASO, non-rapid eye movement (NREM sleep, and REM sleep. We show that individual patient hypnograms contain insufficient number of bouts to adequately describe the transition kinetics, necessitating pooling of data. We compared a control group of individuals free of medications, obstructive sleep apnea (OSA, medical co-morbidities, or sleepiness (n = 374 with mild (n = 496 or severe OSA (n = 338. WASO, REM sleep, and NREM sleep bout durations exhibited multi-exponential temporal dynamics. The presence of OSA accelerated the "decay" rate of NREM and REM sleep bouts, resulting in instability manifesting as shorter bouts and increased number of stage transitions. For WASO bouts, previously attributed to a power law process, a multi-exponential decay described the data well. Simulations demonstrated that a multi-exponential process can mimic a power law distribution.OSA alters sleep architecture dynamics by decreasing the temporal stability of NREM and REM sleep bouts. Multi-exponential fitting is superior to routine mono-exponential fitting, and may thus provide improved predictive metrics of sleep continuity. However, because a single night of sleep contains insufficient transitions to characterize these dynamics, extended monitoring of sleep, probably at home, would be necessary for individualized clinical application.

  14. Sleep apnea: A dental perspective

    Directory of Open Access Journals (Sweden)

    Anil Kumar Nagarajappa

    2015-01-01

    Full Text Available Sleep apnea is an entity characterized by repetitive upper airway obstruction resulting in nocturnal hypoxia and sleep fragmentation. It is recognized as a public health problem and shows detrimental effects on health, such as hypertension, cardiovascular disease, and death. The prevalence rate is 19.5% among men and 7.5% among women in India. Polysomnography remains the gold standard method for diagnosis of sleep apnea and assessment of sleep apnea. Positive pressure therapy is the mainstay therapy of sleep apnea. Other treatment modalities include lifestyle modification, upper airway surgery, and use of an oral appliance. This article reviews the available data on management of sleep apnea.

  15. Sleep, noise and health: Review

    Directory of Open Access Journals (Sweden)

    Mia Zaharna

    2010-01-01

    Full Text Available Sleep is a physiologic recuperative state that may be negatively affected by factors such as psychosocial and work stress as well as external stimuli like noise. Chronic sleep loss is a common problem in today′s society, and it may have significant health repercussions such as cognitive impairment, and depressed mood, and negative effects on cardiovascular, endocrine, and immune function. This article reviews the definition of disturbed sleep versus sleep deprivation as well as the effects of noise on sleep. We review the various health effects of chronic partial sleep loss with a focus on the neuroendocrine/hormonal, cardiovascular, and mental health repercussions.

  16. Perspective on Sleep and Aging

    Directory of Open Access Journals (Sweden)

    Andrew A Monjan

    2010-09-01

    Full Text Available There is a strong body of data directly interrelating sleep problems with mood disorders. There is a growing data base directly associating sleep disorders with attention and memory problems. Motor disorders, especially involving the dopaminergic system, may produce sleep problems, including a possible association between disordered sleep and nocturnal falls. Sleep disorders may be causal conditions for metabolic diseases and increased risk for morbidity and mortality. Sleep and health are directly interrelated. To further probe these issues, especially as related to the aging process, investigators need to utilize tools and concepts from genomics and epigenetics, proteomics, metabolomics, any future ...omics, molecular neuroimaging, and cognitive neuroscience.

  17. Diverse patterns of expression of the cytochrome c oxidase subunit I gene and unassigned reading frames 4 and 5 during the life cycle of Trypanosoma brucei.

    Science.gov (United States)

    Jasmer, D P; Feagin, J E; Stuart, K

    1985-01-01

    Transcription of a maxicircle segment from Trypanosoma brucei 164 that contains nucleotide (nt) sequences corresponding to cytochrome c oxidase subunit I (COI) and unassigned reading frames (URFs) 4 and 5 of other mitochondrial systems was investigated. Two major transcripts that differ in size by ca. 200 nt map to each of the COI and URF4 genes, while a single major transcript maps to URF5. In total RNA, the larger COI transcript is more abundant in procyclic forms (PFs) than in bloodstream forms (BFs), the smaller COI and both URF4 transcripts have similar abundances in both forms, and the single URF5 transcript is more abundant in BF than PF. These patterns of expression differ in poly(A)+ RNA as a result of a higher proportion of poly(A)+ mitochondrial transcripts in PFs than in BFs. In addition, small (300- to 500-nt) RNAs that are transcribed from C-rich sequences located between putative protein-coding genes also exhibit diverse patterns of expression between life cycle stages and differences in polyadenylation in PFs compared with BFs. These observations suggest that multiple processes regulate the differential expression of mitochondrial genes in T. brucei. Images PMID:2427925

  18. Trypanosoma brucei Inhibition by Essential Oils from Medicinal and Aromatic Plants Traditionally Used in Cameroon (Azadirachta indica, Aframomum melegueta, Aframomum daniellii, Clausena anisata, Dichrostachys cinerea and Echinops giganteus).

    Science.gov (United States)

    Kamte, Stephane L Ngahang; Ranjbarian, Farahnaz; Campagnaro, Gustavo Daniel; Nya, Prosper C Biapa; Mbuntcha, Hélène; Woguem, Verlaine; Womeni, Hilaire Macaire; Ta, Léon Azefack; Giordani, Cristiano; Barboni, Luciano; Benelli, Giovanni; Cappellacci, Loredana; Hofer, Anders; Petrelli, Riccardo; Maggi, Filippo

    2017-07-06

    Essential oils are complex mixtures of volatile components produced by the plant secondary metabolism and consist mainly of monoterpenes and sesquiterpenes and, to a minor extent, of aromatic and aliphatic compounds. They are exploited in several fields such as perfumery, food, pharmaceutics, and cosmetics. Essential oils have long-standing uses in the treatment of infectious diseases and parasitosis in humans and animals. In this regard, their therapeutic potential against human African trypanosomiasis (HAT) has not been fully explored. In the present work, we have selected six medicinal and aromatic plants ( Azadirachta indica , Aframomum melegueta , Aframomum daniellii , Clausena anisata , Dichrostachys cinerea , and Echinops giganteus ) traditionally used in Cameroon to treat several disorders, including infections and parasitic diseases, and evaluated the activity of their essential oils against Trypanosma brucei TC221. Their selectivity was also determined with Balb/3T3 (mouse embryonic fibroblast cell line) cells as a reference. The results showed that the essential oils from A. indica , A . daniellii , and E. giganteus were the most active ones, with half maximal inhibitory concentration (IC 50 ) values of 15.21, 7.65, and 10.50 µg/mL, respectively. These essential oils were characterized by different chemical compounds such as sesquiterpene hydrocarbons, monoterpene hydrocarbons, and oxygenated sesquiterpenes. Some of their main components were assayed as well on T. brucei TC221, and their effects were linked to those of essential oils.

  19. Sleep disorders in Parkinson?s disease

    OpenAIRE

    Jahan, Israt; Robert A. Hauser; Sullivan, Kelly L; Miller, Amber; Zesiewicz, Theresa A

    2009-01-01

    Sleep disorders occur commonly in Parkinson?s disease (PD), and reduce quality of life. Sleep-related problems in PD include insomnia, restless legs syndrome, rapid eye movement sleep behavior disorder, sleep apnea, parasomnias, excessive daytime sleepiness, and sleep attacks. This article reviews sleep disorders and their treatment in PD.

  20. ADHD Treatments, Sleep, and Sleep Problems: Complex Associations

    National Research Council Canada - National Science Library

    Stein, Mark A; Weiss, Margaret; Hlavaty, Laura

    2012-01-01

    ADHD, sleep, and ADHD treatments are highly interrelated. In this review, we describe the effects of stimulants and non stimulant medications on sleep in children, adolescents, and adults with ADHD...