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Sample records for brucei gambiense sleeping

  1. Domestic animals as potential reservoir hosts of Trypanosoma brucei gambiense in sleeping sickness foci in Cameroon

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    Njiokou F.

    2010-03-01

    Full Text Available An explanation of the endemic nature and/or the resurgence of Human African Trypanosomiasis (HAT in the historic foci in West and Central Africa may be the existence of an animal reservoir. In some HAT foci, pigs were found infected by Trypanosoma brucei gambiense but the implication of the other domestic animals was not quite evaluated. This study aims to determine the prevalence of T. b. gambiense in domestic animal species (goat, sheep, pig and dog commonly found in the four active HAT foci in Cameroon (Bipindi, Fontem, Campo and Doumé. Blood samples were collected from 307 pigs, 264 goats, 267 sheep and 37 dogs and used for parasitological (QBC, immunological (LiTat 1.3 CATT and molecular (PCR analyses. QBC detected trypanosomes in 3.88 % domestic animals while 22.7 % were sero-positive with LiTat 1.3 CATT tests. Of the 875 animals analysed, 174 (19.88 % harboured T. brucei s.l. DNA, found in each of the four types of animal and in the four localities. The infection rate significantly differed among the animal species (p < 0.0001 and localities (p < 0.0001. The PCR also revealed T. b. gambiense group 1 DNA in 27 (3.08 % domestic animals. The specific infection rates were as follows: sheep (6.74 %, goats (3.08 %, pigs (0.32 % and dogs (0 %. T. b. gambiense was found in 8 (3.92 % animals from Bipindi, 15 (4.83 % from Campo, 4 (2.59 % from Fontem-Center and none from Doumé. The infection rates significantly differed between the localities, and correlated with the intensity of HAT transmission in the foci.

  2. Melarsoprol sensitivity profile of Trypanosoma brucei gambiense isolates from cured and relapsed sleeping sickness patients from the Democratic Republic of the Congo.

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    Patient Pyana Pati

    2014-10-01

    Full Text Available Sleeping sickness caused by Trypanosoma brucei (T.b. gambiense constitutes a serious health problem in sub-Sahara Africa. In some foci, alarmingly high relapse rates were observed in patients treated with melarsoprol, which used to be the first line treatment for patients in the neurological disease stage. Particularly problematic was the situation in Mbuji-Mayi, East Kasai Province in the Democratic Republic of the Congo with a 57% relapse rate compared to a 5% relapse rate in Masi-Manimba, Bandundu Province. The present study aimed at investigating the mechanisms underlying the high relapse rate in Mbuji-Mayi using an extended collection of recently isolated T.b. gambiense strains from Mbuji-Mayi and from Masi-Manimba.Forty five T.b. gambiense strains were used. Forty one were isolated from patients that were cured or relapsed after melarsoprol treatment in Mbuji-Mayi. In vivo drug sensitivity tests provide evidence of reduced melarsoprol sensitivity in these strains. This reduced melarsoprol sensitivity was not attributable to mutations in TbAT1. However, in all these strains, irrespective of the patient treatment outcome, the two aquaglyceroporin (AQP 2 and 3 genes are replaced by chimeric AQP2/3 genes that may be associated with resistance to pentamidine and melarsoprol. The 4 T.b. gambiense strains isolated in Masi-Manimba contain both wild-type AQP2 and a different chimeric AQP2/3. These findings suggest that the reduced in vivo melarsoprol sensitivity of the Mbuji-Mayi strains and the high relapse rates in that sleeping sickness focus are caused by mutations in the AQP2/AQP3 locus and not by mutations in TbAT1.We conclude that mutations in the TbAQP2/3 locus of the local T.b. gambiense strains may explain the high melarsoprol relapse rates in the Mbuji-Mayi focus but other factors must also be involved in the treatment outcome of individual patients.

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

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    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.

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

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    Graf, Fabrice E; Baker, Nicola; Munday, Jane C; de Koning, Harry P; Horn, David; Mäser, Pascal

    2015-08-01

    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.

  5. Untreated human infections by Trypanosoma brucei gambiense are not 100% fatal.

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    Vincent Jamonneau

    Full Text Available The final outcome of infection by Trypanosoma brucei gambiense, the main agent of sleeping sickness, has always been considered as invariably fatal. While scarce and old reports have mentioned cases of self-cure in untreated patients, these studies suffered from the lack of accurate diagnostic tools available at that time. Here, using the most specific and sensitive tools available to date, we report on a long-term follow-up (15 years of a cohort of 50 human African trypanosomiasis (HAT patients from the Ivory Coast among whom 11 refused treatment after their initial diagnosis. In 10 out of 11 subjects who continued to refuse treatment despite repeated visits, parasite clearance was observed using both microscopy and polymerase chain reaction (PCR. Most of these subjects (7/10 also displayed decreasing serological responses, becoming progressively negative to trypanosome variable antigens (LiTat 1.3, 1.5 and 1.6. Hence, in addition to the "classic" lethal outcome of HAT, we show that alternative natural progressions of HAT may occur: progression to an apparently aparasitaemic and asymptomatic infection associated with strong long-lasting serological responses and progression to an apparently spontaneous resolution of infection (with negative results in parasitological tests and PCR associated with a progressive drop in antibody titres as observed in treated cases. While this study does not precisely estimate the frequency of the alternative courses for this infection, it is noteworthy that in the field national control programs encounter a significant proportion of subjects displaying positive serologic test results but negative results in parasitological testing. These findings demonstrate that a number of these subjects display such infection courses. From our point of view, recognising that trypanotolerance exists in humans, as is now widely accepted for animals, is a major step forward for future research in the field of HAT.

  6. Trypanosoma brucei gambiense Type 1 populations from human patients are clonal and display geographical genetic differentiation.

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    Morrison, Liam J; Tait, Andy; McCormack, Gillian; Sweeney, Lindsay; Black, Alana; Truc, Philippe; Likeufack, Anne C L; Turner, C Michael; MacLeod, Annette

    2008-12-01

    We have rigorously tested the hypothesis that Trypanosoma brucei gambiense Type 1 is composed of genetically homogenous populations by examining the parasite population present in Human African Trypanosomiasis (HAT) patients from the Democratic Republic of Congo (DRC) and Cameroon (CAM). We amplified eight microsatellite markers by PCR directly from blood spots on FTA filters, thereby avoiding the significant parasite selection inherent in the traditional isolation techniques of rodent inoculation or in vitro culture. All microsatellite markers were polymorphic, although for four markers there was only polymorphism between the DRC and CAM populations, not within populations, suggesting very limited genetic exchange. Within the largest population from the DRC, Hardy-Weinberg equilibrium is not evident at any loci. This evidence suggests a clonal population. However, there was significant sub-structuring between the DRC and CAM samples (F(ST) = 0.32), indicating that Trypanosoma brucei gambiense Type 1 has genetically distinct clades. The data combine to indicate that genetic exchange plays a very limited role. The finding of distinct clades in different places suggests the possibility that samples from humans with clinical signs represent clonal expansions from an underlying population that requires identifying and characterising.

  7. Diversity and spation distribution of vectors and hosts of T. brucei gambiense in forest zones of Southern Cameroon: Epidemiological implications

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    Massussi, J.A.; Mbida Mbida, J.A.; Djieto-Lordon, C.; Njiokou, F.; Laveissière, C.; Ploeg, van der J.D.

    2010-01-01

    Host and vector distribution of Trypanosoma brucei gambiense was studied in relation to habitat types and seasons. Six (19.35%) of the 31 mammal species recorded in Bipindi were reservoir hosts. Cercopithecus nictitans was confined to the undisturbed forest and the low intensive shifting cultivation

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

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    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.

  9. Trypanosoma brucei gambiense adaptation to different mammalian sera is associated with VSG expression site plasticity.

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    Carlos Cordon-Obras

    Full Text Available Trypanosoma brucei gambiense infection is widely considered an anthroponosis, although it has also been found in wild and domestic animals. Thus, fauna could act as reservoir, constraining the elimination of the parasite in hypo-endemic foci. To better understand the possible maintenance of T. b. gambiense in local fauna and investigate the molecular mechanisms underlying adaptation, we generated adapted cells lines (ACLs by in vitro culture of the parasites in different mammalian sera. Using specific antibodies against the Variant Surface Glycoproteins (VSGs we found that serum ACLs exhibited different VSG variants when maintained in pig, goat or human sera. Although newly detected VSGs were independent of the sera used, the consistent appearance of different VSGs suggested remodelling of the co-transcribed genes at the telomeric Expression Site (VSG-ES. Thus, Expression Site Associated Genes (ESAGs sequences were analysed to investigate possible polymorphism selection. ESAGs 6 and 7 genotypes, encoding the transferrin receptor (TfR, expressed in different ACLs were characterised. In addition, we quantified the ESAG6/7 mRNA levels and analysed transferrin (Tf uptake. Interestingly, the best growth occurred in pig and human serum ACLs, which consistently exhibited a predominant ESAG7 genotype and higher Tf uptake than those obtained in calf and goat sera. We also detected an apparent selection of specific ESAG3 genotypes in the pig and human serum ACLs, suggesting that other ESAGs could be involved in the host adaptation processes. Altogether, these results suggest a model whereby VSG-ES remodelling allows the parasite to express a specific set of ESAGs to provide selective advantages in different hosts. Finally, pig serum ACLs display phenotypic adaptation parameters closely related to human serum ACLs but distinct to parasites grown in calf and goat sera. These results suggest a better suitability of swine to maintain T. b. gambiense infection

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

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    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 Cerrado conservation and sustainable development.

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

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    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.

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

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    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.

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

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    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.

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

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    Graf, Fabrice E; Ludin, Philipp; Wenzler, Tanja; Kaiser, Marcel; Brun, Reto; Pyana, Patient Pati; Büscher, Philippe; de Koning, Harry P; Horn, David; Mäser, Pascal

    2013-01-01

    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.

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

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    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.

  16. Murine Models for Trypanosoma brucei gambiense disease progression--from silent to chronic infections and early brain tropism.

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    Christiane Giroud

    Full Text Available Human African trypanosomiasis (HAT caused by Trypanosoma brucei gambiense remains highly prevalent in west and central Africa and is lethal if left untreated. The major problem is that the disease often evolves toward chronic or asymptomatic forms with low and fluctuating parasitaemia producing apparently aparasitaemic serological suspects who remain untreated because of the toxicity of the chemotherapy. Whether the different types of infections are due to host or parasite factors has been difficult to address, since T. b. gambiense isolated from patients is often not infectious in rodents thus limiting the variety of isolates.T. b. gambiense parasites were outgrown directly from the cerebrospinal fluid of infected patients by in vitro culture and analyzed for their molecular polymorphisms. Experimental murine infections showed that these isolates could be clustered into three groups with different characteristics regarding their in vivo infection properties, immune response and capacity for brain invasion. The first isolate induced a classical chronic infection with a fluctuating blood parasitaemia, an invasion of the central nervous system (CNS, a trypanosome specific-antibody response and death of the animals within 6-8 months. The second group induced a sub-chronic infection resulting in a single wave of parasitaemia after infection, followed by a low parasitaemia with no parasites detected by microscope observations of blood but detected by PCR, and the presence of a specific antibody response. The third isolate induced a silent infection characterised by the absence of microscopically detectable parasites throughout, but infection was detectable by PCR during the whole course of infection. Additionally, specific antibodies were barely detectable when mice were infected with a low number of this group of parasites. In both sub-chronic and chronic infections, most of the mice survived more than one year without major clinical symptoms

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

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    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.

  18. The natural progression of Gambiense sleeping sickness: what is the evidence?

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    Francesco Checchi

    Full Text Available Gambiense human African trypanosomiasis (HAT, sleeping sickness is widely assumed to be 100% pathogenic and fatal. However, reports to the contrary exist, and human trypano-tolerance has been postulated. Furthermore, there is uncertainty about the actual duration of both stage 1 and stage 2 infection, particularly with respect to how long a patient remains infectious. Understanding such basic parameters of HAT infection is essential for optimising control strategies based on case detection. We considered the potential existence and relevance of human trypano-tolerance, and explored the duration of infectiousness, through a review of published evidence on the natural progression of gambiense HAT in the absence of treatment, and biological considerations. Published reports indicate that most gambiense HAT cases are fatal if untreated. Self-resolving and asymptomatic chronic infections probably constitute a minority if they do indeed exist. Chronic carriage, however, deserves further study, as it could seed renewed epidemics after control programmes cease.

  19. The miRNA and mRNA Signatures of Peripheral Blood Cells in Humans Infected with Trypanosoma brucei gambiense.

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    Smiths Lueong

    Full Text Available Simple, reliable tools for diagnosis of human African Trypanosomiases could ease field surveillance and enhance patient care. In particular, current methods to distinguish patients with (stage II and without (stage I brain involvement require samples of cerebrospinal fluid. We describe here an exploratory study to find out whether miRNAs from peripheral blood leukocytes might be useful in diagnosis of human trypanosomiasis, or for determining the stage of the disease. Using microarrays, we measured miRNAs in samples from Trypanosoma brucei gambiense-infected patients (9 stage I, 10 stage II, 8 seronegative parasite-negative controls and 12 seropositive, but parasite-negative subjects. 8 miRNAs (out of 1205 tested showed significantly lower expression in patients than in seronegative, parasite-negative controls, and 1 showed increased expression. There were no clear differences in miRNAs between patients in different disease stages. The miRNA profiles could not distinguish seropositive, but parasitologically negative samples from controls and results within this group did not correlate with those from the trypanolysis test. Some of the regulated miRNAs, or their predicted mRNA targets, were previously reported changed during other infectious diseases or cancer. We conclude that the changes in miRNA profiles of peripheral blood lymphocytes in human African trypanosomiasis are related to immune activation or inflammation, are probably disease-non-specific, and cannot be used to determine the disease stage. The approach has little promise for diagnostics but might yield information about disease pathology.

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

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    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.

  1. Loop-Mediated Isothermal Amplification Test for Trypanosoma gambiense Group 1 with Stem Primers: A Molecular Xenomonitoring Test for Sleeping Sickness

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    Mburugu, Gitonga N.

    2017-01-01

    The World Health Organization has targeted Human African Trypanosomiasis (HAT) for elimination by 2020 with zero incidence by 2030. To achieve and sustain this goal, accurate and easy-to-deploy diagnostic tests for Gambian trypanosomiasis which accounts for over 98% of reported cases will play a crucial role. Most needed will be tools for surveillance of pathogen in vectors (xenomonitoring) since population screening tests are readily available. The development of new tests is expensive and takes a long time while incremental improvement of existing technologies that have potential for xenomonitoring may offer a shorter pathway to tools for HAT surveillance. We have investigated the effect of including a second set of reaction accelerating primers (stem primers) to the standard T. brucei gambiense LAMP test format. The new test format was analyzed with and without outer primers. Amplification was carried out using Rotorgene 6000 and the portable ESE Quant amplification unit capable of real-time data output. The stem LAMP formats indicated shorter time to results (~8 min), were 10–100-fold more sensitive, and indicated higher diagnostic sensitivity and accuracy compared to the standard LAMP test. It was possible to confirm the predicted product using ESE melt curves demonstrating the potential of combining LAMP and real-time technologies as possible tool for HAT molecular xenomonitoring.

  2. Loop-Mediated Isothermal Amplification Test for Trypanosoma gambiense Group 1 with Stem Primers: A Molecular Xenomonitoring Test for Sleeping Sickness

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    Zablon K. Njiru

    2017-01-01

    Full Text Available The World Health Organization has targeted Human African Trypanosomiasis (HAT for elimination by 2020 with zero incidence by 2030. To achieve and sustain this goal, accurate and easy-to-deploy diagnostic tests for Gambian trypanosomiasis which accounts for over 98% of reported cases will play a crucial role. Most needed will be tools for surveillance of pathogen in vectors (xenomonitoring since population screening tests are readily available. The development of new tests is expensive and takes a long time while incremental improvement of existing technologies that have potential for xenomonitoring may offer a shorter pathway to tools for HAT surveillance. We have investigated the effect of including a second set of reaction accelerating primers (stem primers to the standard T. brucei gambiense LAMP test format. The new test format was analyzed with and without outer primers. Amplification was carried out using Rotorgene 6000 and the portable ESE Quant amplification unit capable of real-time data output. The stem LAMP formats indicated shorter time to results (~8 min, were 10–100-fold more sensitive, and indicated higher diagnostic sensitivity and accuracy compared to the standard LAMP test. It was possible to confirm the predicted product using ESE melt curves demonstrating the potential of combining LAMP and real-time technologies as possible tool for HAT molecular xenomonitoring.

  3. 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

    2016-01-01

    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 (ptrypanosomiasis. PMID:27855164

  4. Wild chimpanzees are infected by Trypanosoma brucei

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    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.

  5. Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness).

    Science.gov (United States)

    Kennedy, Peter Ge

    2013-02-01

    Human African trypanosomiasis, or sleeping sickness, is caused by infection with parasites of the genus Trypanosoma, transmitted by the tsetse fly. The disease has two forms, Trypanosoma brucei (T b) rhodesiense and T b gambiense; and is almost always fatal if untreated. Despite a recent reduction in the number of reported cases, patients with African trypanosomiasis continue to present major challenges to clinicians. Because treatment for CNS-stage disease can be very toxic, diagnostic staging to distinguish early-stage from late-stage disease when the CNS in invaded is crucial but remains problematic. Melarsoprol is the only available treatment for late-stage T b rhodesiense infection, but can be lethal to 5% of patients owing to post-treatment reactive encephalopathy. Eflornithine combined with nifurtimox is the first-line treatment for late-stage T b gambiense. New drugs are in the pipeline for treatment of CNS human African trypanosomiasis, giving rise to cautious optimism.

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

    Science.gov (United States)

    Laperchia, Claudia; Palomba, Maria; Seke Etet, Paul F.; Rodgers, Jean; Bradley, Barbara; Montague, Paul; Grassi-Zucconi, Gigliola; Bentivoglio, Marina

    2016-01-01

    Background 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. Methodology 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. Principal findings 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. Conclusion 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. PMID:28002454

  7. Survey on Trypanosoma spp. infection of dogs in Gabon and its epidemiological implications for sleeping sickness.

    Science.gov (United States)

    Watier-Grillot, S; Herder, S; Marié, J-L; Bourry, O; Cuny, G; Davoust, B

    2016-05-01

    This survey screened native dogs (Canis familiaris) in Gabon (Africa) for trypanosome infection. A total of 376 apparently healthy dogs, divided into two populations, were examined. The first group included 252 semi-domesticated dogs inhabiting 16 villages of the Ogooué-Ivindo Province, a rural inland area in northeast Gabon, and the second group 124 dogs belonging to protection companies or families from Libreville (n = 113) and Port-Gentil (n = 11), in the coastal area of Gabon. Both study areas include active or former foci of sleeping sickness in Gabon. Molecular testing (polymerase chain reaction) was performed on blood samples from dogs in both groups. All dogs were negative for T. congolense ("savanna type" and "forest type"). Eighteen dogs (4.7%), however, tested positive for T. brucei s.l.: 3% (8/252) were from the Ogooué-Ivindo Province, and 8% (10/124) from the coastal area. These animals may be potential reservoirs of the parasite T. brucei gambiense, responsible for human African trypanosomiasis. This hypothesis, as well as the role of the dog as a sentinel of human infection by T. brucei gambiense, should be investigated in further studies.

  8. Mechanism of Trypanosoma brucei gambiense resistance to human serum

    DEFF Research Database (Denmark)

    Uzureau, Pierrick; Uzureau, Sophie; Lecordier, Laurence

    2013-01-01

    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...

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

    Directory of Open Access Journals (Sweden)

    Jennifer J Palmer

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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

  10. 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

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    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

  11. The continuing problem of human African trypanosomiasis (sleeping sickness).

    Science.gov (United States)

    Kennedy, Peter G E

    2008-08-01

    Human African trypanosomiasis, also known as sleeping sickness, is a neglected disease, and it continues to pose a major threat to 60 million people in 36 countries in sub-Saharan Africa. Transmitted by the bite of the tsetse fly, the disease is caused by protozoan parasites of the genus Trypanosoma and comes in two types: East African human African trypanosomiasis caused by Trypanosoma brucei rhodesiense and the West African form caused by Trypanosoma brucei gambiense. There is an early or hemolymphatic stage and a late or encephalitic stage, when the parasites cross the blood-brain barrier to invade the central nervous system. Two critical current issues are disease staging and drug therapy, especially for late-stage disease. Lumbar puncture to analyze cerebrospinal fluid will remain the only method of disease staging until reliable noninvasive methods are developed, but there is no widespread consensus as to what exactly defines biologically central nervous system disease or what specific cerebrospinal fluid findings should justify drug therapy for late-stage involvement. All four main drugs used for human African trypanosomiasis are toxic, and melarsoprol, the only drug that is effective for both types of central nervous system disease, is so toxic that it kills 5% of patients who receive it. Eflornithine, alone or combined with nifurtimox, is being used increasingly as first-line therapy for gambiense disease. There is a pressing need for an effective, safe oral drug for both stages of the disease, but this will require a significant increase in investment for new drug discovery from Western governments and the pharmaceutical industry.

  12. Structural and Functional Highlights of Vacuolar Soluble Protein 1 from Pathogen Trypanosoma brucei brucei.

    Science.gov (United States)

    Jamwal, Abhishek; Round, Adam R; Bannwarth, Ludovic; Venien-Bryan, Catherine; Belrhali, Hassan; Yogavel, Manickam; Sharma, Amit

    2015-12-18

    Trypanosoma brucei (T. brucei) is responsible for the fatal human disease called African trypanosomiasis, or sleeping sickness. The causative parasite, Trypanosoma, encodes soluble versions of inorganic pyrophosphatases (PPase), also called vacuolar soluble proteins (VSPs), which are localized to its acidocalcisomes. The latter are acidic membrane-enclosed organelles rich in polyphosphate chains and divalent cations whose significance in these parasites remains unclear. We here report the crystal structure of T. brucei brucei acidocalcisomal PPases in a ternary complex with Mg(2+) and imidodiphosphate. The crystal structure reveals a novel structural architecture distinct from known class I PPases in its tetrameric oligomeric state in which a fused EF hand domain arranges around the catalytic PPase domain. This unprecedented assembly evident from TbbVSP1 crystal structure is further confirmed by SAXS and TEM data. SAXS data suggest structural flexibility in EF hand domains indicative of conformational plasticity within TbbVSP1.

  13. Structural and Functional Highlights of Vacuolar Soluble Protein 1 from Pathogen Trypanosoma brucei brucei*

    Science.gov (United States)

    Jamwal, Abhishek; Round, Adam R.; Bannwarth, Ludovic; Venien-Bryan, Catherine; Belrhali, Hassan; Yogavel, Manickam; Sharma, Amit

    2015-01-01

    Trypanosoma brucei (T. brucei) is responsible for the fatal human disease called African trypanosomiasis, or sleeping sickness. The causative parasite, Trypanosoma, encodes soluble versions of inorganic pyrophosphatases (PPase), also called vacuolar soluble proteins (VSPs), which are localized to its acidocalcisomes. The latter are acidic membrane-enclosed organelles rich in polyphosphate chains and divalent cations whose significance in these parasites remains unclear. We here report the crystal structure of T. brucei brucei acidocalcisomal PPases in a ternary complex with Mg2+ and imidodiphosphate. The crystal structure reveals a novel structural architecture distinct from known class I PPases in its tetrameric oligomeric state in which a fused EF hand domain arranges around the catalytic PPase domain. This unprecedented assembly evident from TbbVSP1 crystal structure is further confirmed by SAXS and TEM data. SAXS data suggest structural flexibility in EF hand domains indicative of conformational plasticity within TbbVSP1. PMID:26494625

  14. Gambiense human african trypanosomiasis and immunological memory: effect on phenotypic lymphocyte profiles and humoral immunity.

    Science.gov (United States)

    Lejon, Veerle; Mumba Ngoyi, Dieudonné; Kestens, Luc; Boel, Luc; Barbé, Barbara; Kande Betu, Victor; van Griensven, Johan; Bottieau, Emmanuel; Muyembe Tamfum, Jean-Jacques; Jacobs, Jan; Büscher, Philippe

    2014-03-01

    In mice, experimental infection with Trypanosoma brucei causes decreased bone marrow B-cell development, abolished splenic B-cell maturation and loss of antibody mediated protection including vaccine induced memory responses. Nothing is known about this phenomenon in human African trypanosomiasis (HAT), but if occurring, it would imply the need of revaccination of HAT patients after therapy and abolish hope for a HAT vaccine. The effect of gambiense HAT on peripheral blood memory T- and B-cells and on innate and vaccine induced antibody levels was examined. The percentage of memory B- and T-cells was quantified in peripheral blood, prospectively collected in DR Congo from 117 Trypanosoma brucei gambiense infected HAT patients before and six months after treatment and 117 controls at the same time points. Antibodies against carbohydrate antigens on red blood cells and against measles were quantified. Before treatment, significantly higher percentages of memory B-cells, mainly T-independent memory B-cells, were observed in HAT patients compared to controls (CD20+CD27+IgM+, 13.0% versus 2.0%, p<0.001). The percentage of memory T-cells, mainly early effector/memory T-cells, was higher in HAT (CD3+CD45RO+CD27+, 19.4% versus 16.7%, p = 0.003). After treatment, the percentage of memory T-cells normalized, the percentage of memory B-cells did not. The median anti-red blood cell carbohydrate IgM level was one titer lower in HAT patients than in controls (p<0.004), and partially normalized after treatment. Anti-measles antibody concentrations were lower in HAT patients than in controls (medians of 1500 versus 2250 mIU/ml, p = 0.02), and remained so after treatment, but were above the cut-off level assumed to provide protection in 94.8% of HAT patients, before and after treatment (versus 98.3% of controls, p = 0.3). Although functionality of the B-cells was not verified, the results suggest that immunity was conserved in T.b. gambiense infected HAT patients and

  15. Analysis of risk factors for T. brucei rhodesiense sleeping sickness within villages in south-east Uganda

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    Odiit Martin

    2008-06-01

    Full Text Available Abstract Background Sleeping sickness (HAT caused by T.b. rhodesiense is a major veterinary and human public health problem in Uganda. Previous studies have investigated spatial risk factors for T.b. rhodesiense at large geographic scales, but none have properly investigated such risk factors at small scales, i.e. within affected villages. In the present work, we use a case-control methodology to analyse both behavioural and spatial risk factors for HAT in an endemic area. Methods The present study investigates behavioural and occupational risk factors for infection with HAT within villages using a questionnaire-based case-control study conducted in 17 villages endemic for HAT in SE Uganda, and spatial risk factors in 4 high risk villages. For the spatial analysis, the location of homesteads with one or more cases of HAT up to three years prior to the beginning of the study was compared to all non-case homesteads. Analysing spatial associations with respect to irregularly shaped geographical objects required the development of a new approach to geographical analysis in combination with a logistic regression model. Results The study was able to identify, among other behavioural risk factors, having a family member with a history of HAT (p = 0.001 as well as proximity of a homestead to a nearby wetland area (p Conclusion Spatial risk factors for HAT are maintained across geographical scales; this consistency is useful in the design of decision support tools for intervention and prevention of the disease. Familial aggregation of cases was confirmed for T. b. rhodesiense HAT in the study and probably results from shared behavioural and spatial risk factors amongmembers of a household.

  16. 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.

  17. Identifying transmission cycles at the human-animal interface: the role of animal reservoirs in maintaining gambiense human african trypanosomiasis.

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    Sebastian Funk

    Full Text Available Many infections can be transmitted between animals and humans. The epidemiological roles of different species can vary from important reservoirs to dead-end hosts. Here, we present a method to identify transmission cycles in different combinations of species from field data. We used this method to synthesise epidemiological and ecological data from Bipindi, Cameroon, a historical focus of gambiense Human African Trypanosomiasis (HAT, sleeping sickness, a disease that has often been considered to be maintained mainly by humans. We estimated the basic reproduction number [Formula: see text] of gambiense HAT in Bipindi and evaluated the potential for transmission in the absence of human cases. We found that under the assumption of random mixing between vectors and hosts, gambiense HAT could not be maintained in this focus without the contribution of animals. This result remains robust under extensive sensitivity analysis. When using the distributions of species among habitats to estimate the amount of mixing between those species, we found indications for an independent transmission cycle in wild animals. Stochastic simulation of the system confirmed that unless vectors moved between species very rarely, reintroduction would usually occur shortly after elimination of the infection from human populations. This suggests that elimination strategies may have to be reconsidered as targeting human cases alone would be insufficient for control, and reintroduction from animal reservoirs would remain a threat. Our approach is broadly applicable and could reveal animal reservoirs critical to the control of other infectious diseases.

  18. Sleeping sickness

    Science.gov (United States)

    ... include: Eflornithine (for T. b. gambiense only) Melarsoprol Pentamidine (for T. b. gambiense only) Suramin (Antrypol) Some ... Pentamidine injections protect against T. b. gambiense, but not against T. b. rhodesiense . Because this medicine is ...

  19. A luciferase based viability assay for ATP detection in 384-well format for high throughput whole cell screening of Trypanosoma brucei brucei bloodstream form strain 427

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    Avery Vicky M

    2009-11-01

    Full Text Available Abstract Background Human African Trypanosomiasis (HAT is caused by two trypanosome species, Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. Current drugs available for the treatment of HAT have significant issues related to toxicity, administration regimes with limited effectiveness across species and disease stages, thus there is a considerable need to find alternative drugs. A well recognised approach to identify new drug candidates is high throughput screening (HTS of large compound library collections. Results We describe here the development of a luciferase based viability assay in 384-well plate format suitable for HTS of T.b.brucei. The parameters that were explored to determine the final HTS assay conditions are described in detail and include DMSO tolerability, Z', diluents and cell inoculum density. Reference compound activities were determined for diminazene, staurosporine and pentamidine and compared to previously published IC50 data obtained. The assay has a comparable sensitivity to reference drugs and is more cost effective than the 96-well format currently reported for T.b.brucei. Conclusion Due to the reproducibility and sensitivity of this assay it is recommended for potential HTS application. As it is commercially available this assay can also be utilised in many laboratories for both large and small scale screening.

  20. Structures of Trypanosoma brucei methionyl-tRNA synthetase with urea-based inhibitors provide guidance for drug design against sleeping sickness.

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    Cho Yeow Koh

    2014-04-01

    Full Text Available Methionyl-tRNA synthetase of Trypanosoma brucei (TbMetRS is an important target in the development of new antitrypanosomal drugs. The enzyme is essential, highly flexible and displaying a large degree of changes in protein domains and binding pockets in the presence of substrate, product and inhibitors. Targeting this protein will benefit from a profound understanding of how its structure adapts to ligand binding. A series of urea-based inhibitors (UBIs has been developed with IC50 values as low as 19 nM against the enzyme. The UBIs were shown to be orally available and permeable through the blood-brain barrier, and are therefore candidates for development of drugs for the treatment of late stage human African trypanosomiasis. Here, we expand the structural diversity of inhibitors from the previously reported collection and tested for their inhibitory effect on TbMetRS and on the growth of T. brucei cells. The binding modes and binding pockets of 14 UBIs are revealed by determination of their crystal structures in complex with TbMetRS at resolutions between 2.2 Å to 2.9 Å. The structures show binding of the UBIs through conformational selection, including occupancy of the enlarged methionine pocket and the auxiliary pocket. General principles underlying the affinity of UBIs for TbMetRS are derived from these structures, in particular the optimum way to fill the two binding pockets. The conserved auxiliary pocket might play a role in binding tRNA. In addition, a crystal structure of a ternary TbMetRS•inhibitor•AMPPCP complex indicates that the UBIs are not competing with ATP for binding, instead are interacting with ATP through hydrogen bond. This suggests a possibility that a general 'ATP-engaging' binding mode can be utilized for the design and development of inhibitors targeting tRNA synthetases of other disease-causing pathogen.

  1. 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...

  2. Motility modes of the parasite Trypanosoma brucei

    Science.gov (United States)

    Temel, Fatma Zeynep; Qu, Zijie; McAllaster, Michael; de Graffenried, Christopher; Breuer, Kenneth

    2015-11-01

    The parasitic single-celled protozoan Trypanosoma brucei causes African Sleeping Sickness, which is a fatal disease in humans and animals that threatens more than 60 million people in 36 African countries. Cell motility plays a critical role in the developmental phases and dissemination of the parasite. Unlike many other motile cells such as bacteria Escherichia coli or Caulobacter crescentus, the flagellum of T. brucei is attached along the length of its awl-like body, producing a unique mode of motility that is not fully understood or characterized. Here, we report on the motility of T. brucei, which swims using its single flagellum employing both rotating and undulating propulsion modes. We tracked cells in real-time in three dimensions using fluorescent microscopy. Data obtained from experiments using both short-term tracking within the field of view and long-term tracking using a tracking microscope were analyzed. Motility modes and swimming speed were analyzed as functions of cell size, rotation rate and undulation pattern. Research supported by NSF.

  3. 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 ...

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

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    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.

  5. 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

    2011-05-01

    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 7 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 7 vivax and T congolense "forest type" in Bipindi and Fontem-Center indicate their intense transmission in these foci.

  6. Sleep

    Science.gov (United States)

    ... NICHD Research Information Clinical Trials Resources and Publications Sleep: Condition Information Skip sharing on social media links Share this: Page Content What is sleep? Sleep is a period of unconsciousness during which ...

  7. Treatment options for second-stage gambiense human African trypanosomiasis.

    Science.gov (United States)

    Eperon, Gilles; Balasegaram, Manica; Potet, Julien; Mowbray, Charles; Valverde, Olaf; Chappuis, François

    2014-11-01

    Treatment of second-stage gambiense human African trypanosomiasis relied on toxic arsenic-based derivatives for over 50 years. The availability and subsequent use of eflornithine, initially in monotherapy and more recently in combination with nifurtimox (NECT), has drastically improved the prognosis of treated patients. However, NECT logistic and nursing requirements remain obstacles to its deployment and use in peripheral health structures in rural sub-Saharan Africa. Two oral compounds, fexinidazole and SCYX-7158, are currently in clinical development. The main scope of this article is to discuss the potential impact of new oral therapies to improve diagnosis-treatment algorithms and patients' access to treatment, and to contribute to reach the objectives of the recently launched gambiense human African trypanosomiasis elimination program.

  8. 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

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

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    Nimpaye H.

    2011-05-01

    Full Text Available 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.

  10. Trypanosoma brucei gambiense Spliced Leader RNA Is a More Specific Marker for Cure of Human African Trypanosomiasis Than T. b. gambiense DNA.

    Science.gov (United States)

    Ilboudo, Hamidou; Camara, Oumou; Ravel, Sophie; Bucheton, Bruno; Lejon, Veerle; Camara, Mamadou; Kaboré, Jacques; Jamonneau, Vincent; Deborggraeve, Stijn

    2015-12-15

    To assess the efficacy of treatment for human African trypanosomiasis, accurate tests that can discriminate relapse from cure are needed. We report the first data that the spliced leader (SL) RNA is a more specific marker for cure of human African trypanosomiasis than parasite DNA. In blood samples obtained from 61 patients in whom human African trypanosomiasis was cured, SL RNA detection had specificities of 98.4%-100%, while DNA detection had a specificity of only 77%. Data from our proof-of-concept study show that SL RNA detection has high potential as a test of cure.

  11. Biosynthesis and uptake of thiamine (vitamin B1) in bloodstream form Trypanosoma brucei brucei and interference of the vitamin with melarsen oxide activity.

    Science.gov (United States)

    Stoffel, Sabine A; Rodenko, Boris; Schweingruber, Anne-Marie; Mäser, Pascal; de Koning, Harry P; Schweingruber, M Ernst

    2006-02-01

    Bloodstream forms of Trypanosoma brucei brucei were cultivated in the presence and absence of thiamine (vitamin B1) and pyridoxine (vitamin B6). The vitamins do not change growth behaviour, indicating that Trypanosoma brucei is prototrophic for the two vitamins even though in silico no bona-fide thiamine-biosynthetic genes could be identified in the T. brucei genome. Intracellularly, thiamine is mainly present in its diphosphate form. We were unable to detect significant uptake of [3H]thiamine and structural thiamine analogues such as pyrithiamine, oxithiamine and amprolium were not toxic for the bloodstream forms of T. brucei, indicating that the organism does not have an efficient uptake system for thiamine and its analogues. We have previously shown that, in the fission yeast Saccharomyces pombe, the toxicity of melarsen oxide, the pharmacologically active derivative of the frontline sleeping sickness drug melarsoprol, is abolished by thiamine and the drug is taken up by a thiamine-regulated membrane protein which is responsible for the utilization of thiamine. We show here that thiamine also has weak effects on melarsen oxide-induced growth inhibition and lysis in T. brucei. These effects were consistent with a low affinity of thiamine for the P2 adenosine transporter that is responsible for uptake of melaminophenyl arsenicals in African trypanosomes.

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

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    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.

  13. T rypanosoma brucei histone H1 inhibits RNA polymerase I transcription and is important for parasite fitness in vivo

    OpenAIRE

    Pena, Ana C.; Pimentel, Mafalda R; Manso, Helena; Vaz-Drago, Rita; Pinto-Neves, Daniel; Aresta-Branco, Francisco; Rijo-Ferreira, Filipa; Guegan, Fabien; Pedro Coelho, Luis; Carmo-Fonseca, Maria; Barbosa-Morais, Nuno L.; Figueiredo, Luisa M.

    2014-01-01

    T rypanosoma brucei is a unicellular parasite that causes sleeping sickness in humans. Most of its transcription is constitutive and driven by RNA polymerase II. RNA polymerase I (Pol I) transcribes not only ribosomal RNA genes, but also protein-encoding genes, including variant surface glycoproteins (VSGs) and procyclins. In T . brucei, histone H1 (H1) is required for VSG silencing and chromatin condensation. However, whether H1 has a genome-wide role in transcription is unknown. Here, using...

  14. 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...

  15. Effect of ivermectin on Trypanosoma brucei brucei in experimentally infected mice

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    Udensi K. Udensi & A.F. Fagbenro-Beyioku

    2012-09-01

    Full Text Available Background & objectives: Human and livestock African trypanosomiasis, otherwise known as sleeping sickness,is a neglected tropical disease of public health importance in west and central Africa. In view of the adverse sideeffects of the antitrypanosomal drugs, the relatively few side effects observed in ivermectin use, and becauseboth onchocerciasis and typanosomiasis occur in overlapping foci in Africa, it would be desirable if the ivermectinthat has been used successfully on onchocerciasis management could also be used in the control and treatmentof trypanosomiasis.Method: In this study, prophylactic and therapeutic effects of ivermectin (Mectizan were investigated in albinomice infected with a Nigerian strain of Trypanosoma brucei brucei.Results: A 300 μg/ml/kg dose had the most effective impact because it showed the highest mean survival time of12 days in both the treatment and prophylactic groups of mice. This dose also enhanced the defence capacity ofthe treated groups. It also had positive influence on the packed cell volume (PCV and the state of anaemia inthe trypanosome infected mice, hence, improving their survivability.Interpretation & conclusions: Our report indicates that using the 300 μg/ml/kg dose of ivermectin increases themean survival period from 5 to 12 days. This suggests that ivermectin could be possibly used in the treatment oftrypanosomiasis. Further studies will be required to show whether proper treatment may entail a single dose, asused in this study; an increased number of doses, or combinations with other drugs.

  16. 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. PMID:28082973

  17. Single molecule analysis of Trypanosoma brucei DNA replication dynamics.

    Science.gov (United States)

    Calderano, Simone Guedes; Drosopoulos, William C; Quaresma, Marina Mônaco; Marques, Catarina A; Kosiyatrakul, Settapong; McCulloch, Richard; Schildkraut, Carl L; Elias, Maria Carolina

    2015-03-11

    Eukaryotic genome duplication relies on origins of replication, distributed over multiple chromosomes, to initiate DNA replication. A recent genome-wide analysis of Trypanosoma brucei, the etiological agent of sleeping sickness, localized its replication origins to the boundaries of multigenic transcription units. To better understand genomic replication in this organism, we examined replication by single molecule analysis of replicated DNA. We determined the average speed of replication forks of procyclic and bloodstream form cells and we found that T. brucei DNA replication rate is similar to rates seen in other eukaryotes. We also analyzed the replication dynamics of a central region of chromosome 1 in procyclic forms. We present evidence for replication terminating within the central part of the chromosome and thus emanating from both sides, suggesting a previously unmapped origin toward the 5' extremity of chromosome 1. Also, termination is not at a fixed location in chromosome 1, but is rather variable. Importantly, we found a replication origin located near an ORC1/CDC6 binding site that is detected after replicative stress induced by hydroxyurea treatment, suggesting it may be a dormant origin activated in response to replicative stress. Collectively, our findings support the existence of more replication origins in T. brucei than previously appreciated.

  18. Comparative analysis of the kinomes of three pathogenic trypanosomatids: Leishmania major, Trypanosoma brucei and Trypanosoma cruzi

    OpenAIRE

    Parsons, Marilyn; Worthey, Elizabeth A.; Ward, Pauline N; Mottram, Jeremy C.

    2005-01-01

    Background The trypanosomatids Leishmania major, Trypanosoma brucei and Trypanosoma cruzi cause some of the most debilitating diseases of humankind: cutaneous leishmaniasis, African sleeping sickness, and Chagas disease. These protozoa possess complex life cycles that involve development in mammalian and insect hosts, and a tightly coordinated cell cycle ensures propagation of the highly polarized cells. However, the ways in which the parasites respond to their environment and coordinate intr...

  19. 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.

  20. The journey towards elimination of gambiense human African trypanosomiasis: not far, nor easy.

    Science.gov (United States)

    Franco, J R; Simarro, P P; Diarra, A; Ruiz-Postigo, J A; Jannin, J G

    2014-05-01

    Considering the epidemic situation of gambiense human African trypanosomiasis (HAT) at the end of the twentieth century, the World Health Organization (WHO) and partners strengthened disease control and surveillance. Over the last 15 years, the activities implemented through the National Control Programmes have brought gambiense HAT under control and now its elimination is deemed as an achievable goal. In 2012, WHO targeted gambiense HAT for elimination as a public health problem by 2020. The final goal will be the sustainable disease elimination by 2030, defined as the interruption of the transmission of gambiense HAT. The elimination is considered feasible, because of the epidemiological vulnerability of the disease, the current state of control, the availability of strategies and tools and international commitment and political will. Integration of activities in the health system is needed to ensure the sustainability of the elimination. The development of user-friendly diagnostic and treatment tools will facilitate the integration process. Adequate funding is needed to implement activities, but also to support research that will make the elimination sustainable. A long-term commitment by donors is needed and ownership of the process by endemic countries is critical.

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

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    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

  2. A search for Trypanosoma brucei rhodesiense diagnostic antigens by proteomic screening and targeted cloning.

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    Theresa Manful

    Full Text Available BACKGROUND: The only available diagnostic method for East African trypanosomiasis is light microscopy of blood samples. A simple immunodiagnostic would greatly aid trypanosomiasis control. METHODOLOGY AND PRINCIPAL FINDINGS: To find trypanosome proteins that are specifically recognised by sera from human sleeping sickness patients, we have screened the Trypanosoma brucei brucei proteome by Western blotting. Using cytosolic, cytoskeletal and glycosomal fractions, we found that the vast majority of abundant trypanosome proteins is not specifically recognised by patient sera. We identified phosphoglycerate kinase (PGKC, heat shock protein (HSP70, and histones H2B and H3 as possible candidate diagnostic antigens. These proteins, plus paraflagellar rod protein 1, rhodesain (a cysteine protease, and an extracellular fragment of the Trypanosoma brucei nucleoside transporter TbNT10, were expressed in E. coli and tested for reactivity with patient and control sera. Only TbHSP70 was preferentially recognized by patient sera, but the sensitivity and specificity were insufficient for use of TbHSP70 alone as a diagnostic. Immunoprecipitation using a native protein extract revealed no specifically reacting proteins. CONCLUSIONS: No abundant T. brucei soluble, glycosomal or cytoskeletal protein is likely to be useful in diagnosis. To find useful diagnostic antigens it will therefore be necessary to use more sophisticated proteomic methods, or to test a very large panel of candidate proteins.

  3. Ribose 5-phosphate isomerase B knockdown compromises Trypanosoma brucei bloodstream form infectivity.

    Science.gov (United States)

    Loureiro, Inês; Faria, Joana; Clayton, Christine; Macedo-Ribeiro, Sandra; Santarém, Nuno; Roy, Nilanjan; Cordeiro-da-Siva, Anabela; Tavares, Joana

    2015-01-01

    Ribose 5-phosphate isomerase is an enzyme involved in the non-oxidative branch of the pentose phosphate pathway, and catalyzes the inter-conversion of D-ribose 5-phosphate and D-ribulose 5-phosphate. Trypanosomatids, including the agent of African sleeping sickness namely Trypanosoma brucei, have a type B ribose-5-phosphate isomerase. This enzyme is absent from humans, which have a structurally unrelated ribose 5-phosphate isomerase type A, and therefore has been proposed as an attractive drug target waiting further characterization. In this study, Trypanosoma brucei ribose 5-phosphate isomerase B showed in vitro isomerase activity. RNAi against this enzyme reduced parasites' in vitro growth, and more importantly, bloodstream forms infectivity. Mice infected with induced RNAi clones exhibited lower parasitaemia and a prolonged survival compared to control mice. Phenotypic reversion was achieved by complementing induced RNAi clones with an ectopic copy of Trypanosoma cruzi gene. Our results present the first functional characterization of Trypanosoma brucei ribose 5-phosphate isomerase B, and show the relevance of an enzyme belonging to the non-oxidative branch of the pentose phosphate pathway in the context of Trypanosoma brucei infection.

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

    Science.gov (United States)

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

    2015-11-01

    The flagellate Trypanosoma brucei causes sleeping sickness in humans and nagana in animals. Only a few drugs are registered to treat trypanosomiasis, but those drugs show severe side effects. Also, because some pathogen strains have become resistant, new strategies are urgently needed to combat this parasitic disease. An underexplored possibility is the application of combinations of several trypanocidal agents, which may potentiate their trypanocidal activity in a synergistic fashion. 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. Alkaloids were selected that affect different molecular targets: berberine and chelerythrine (intercalation of DNA), piperine (induction of apoptosis), vinblastine (inhibition of microtubule assembly), emetine (intercalation of DNA, inhibition of protein biosynthesis), homoharringtonine (inhibition of protein biosynthesis), and digitonin (membrane permeabilization and uptake facilitation of polar compounds). Most combinations resulted in an enhanced trypanocidal effect. The addition of digitonin significantly stimulated the activity of almost all alkaloids against trypanosomes. The strongest effect was measured in a combination of digitonin with vinblastine. The highest dose reduction indexes (DRI) were measured in the two-drug combination of digitonin or piperine with vinblastine, where the dose of vinblastine could be reduced 9.07-fold or 7.05-fold, respectively. The synergistic effects of mutual combinations of alkaloids and of alkaloids with digitonin present a new avenue to treat trypanosomiasis but one which needs to be corroborated in future animal experiments.

  5. Localization of serum resistance-associated protein in Trypanosoma brucei rhodesiense and transgenic Trypanosoma brucei brucei.

    Science.gov (United States)

    Bart, Jean-Mathieu; Cordon-Obras, Carlos; Vidal, Isabel; Reed, Jennifer; Perez-Pastrana, Esperanza; Cuevas, Laureano; Field, Mark C; Carrington, Mark; Navarro, Miguel

    2015-10-01

    African trypanosomes infect a broad range of mammals, but humans and some higher primates are protected by serum trypanosome lytic factors that contain apolipoprotein L1 (ApoL1). In the human-infective subspecies of Trypanosoma brucei, Trypanosoma brucei rhodesiense, a gene product derived from the variant surface glycoprotein gene family member, serum resistance-associated protein (SRA protein), protects against ApoL1-mediated lysis. Protection against trypanosome lytic factor requires the direct interaction between SRA protein and ApoL1 within the endocytic apparatus of the trypanosome, but some uncertainty remains as to the precise mechanism and location of this interaction. In order to provide more insight into the mechanism of SRA-mediated resistance to trypanosome lytic factor, we assessed the localization of SRA in T. b. rhodesiense EATRO3 using a novel monoclonal antibody raised against SRA together with a set of well-characterized endosomal markers. By three-dimensional deconvolved immunofluorescence single-cell analysis, combined with double-labelling immunoelectron microscopy, we found that ≈ 50% of SRA protein localized to the lysosome, with the remaining population being distributed through the endocytic pathway, but apparently absent from the flagellar pocket membrane. These data suggest that the SRA/trypanolytic factor interaction is intracellular, with the concentration within the endosomes potentially crucial for ensuring a high efficiency.

  6. Anti-trypanosomal effect of Peristrophe bicalyculata extract on Trypanosoma brucei brucei-infected rats

    Institute of Scientific and Technical Information of China (English)

    Abdulazeez Mansurah Abimbola; Ibrahim Abdulrazak Baba; Edibo Zakari Yenusa; Sidali Joseph Omanibe; Idris Habeeb Oladimeji

    2013-01-01

    Objective: To investigate the in vitro and in vivo effect of whole plant extracts of Peristrophe bicalyculata on Trypanosoma brucei brucei-infected rats. Methods: The experiment was divided into two phases: In the first phase, the anti-trypanosomal activity of the hot water, cold water, methanol and butanol extracts of the whole plant were determined by incubating with Trypanosoma brucei brucei. The cold water extract was partially-purified and the anti-trypanosomal activity of the fractions determined. In the second phase, Trypanosoma brucei brucei-infected rats were treated with fraction 2c for nine days. Packed cell volume (PCV), high density lipoprotein (HDL), low density lipoprotein (LDL), total cholesterol (TC), triacylglycerol (TAG), aspartate aminotransferase, alanine aminotransferases (ALT), alkaline phosphatase (ALP), total and direct bilirubin levels were determined at the end of the experiment. Results:Cold water extract immobilized 90%of the parasites after 60 min of incubation, and fraction 2c completely immobilized the parasites after 35 min. It significantly increased PCV in Trypanosoma brucei brucei-infected rats. Decreased TC, TAG, HDL and LDL levels of infected rats increased significantly when rats were treated with the fraction, while elevated levels of total bilirubin and ALT also decreased. The difference in urea, direct bilirubin and ALP was not significant when infected rats were compared to rats in other groups. Conclusions:The ability of the plant to ameliorate the infection-induced biochemical changes calls for detailed investigation of the potentials of the plant for antitrypanosomiasis drug delivery.

  7. Mutational analysis of Trypanosoma brucei RNA editing ligase reveals regions critical for interaction with KREPA2.

    Directory of Open Access Journals (Sweden)

    Vaibhav Mehta

    Full Text Available The Trypanosoma brucei parasite causes the vector-borne disease African sleeping sickness. Mitochondrial mRNAs of T. brucei undergo posttranscriptional RNA editing to make mature, functional mRNAs. The final step of this process is catalyzed by the essential ligase, T. brucei RNA Editing Ligase 1 (TbREL1 and the closely related T. brucei RNA Editing Ligase 2 (TbREL2. While other ligases such as T7 DNA ligase have both a catalytic and an oligonucleotide/oligosaccharide-binding (OB-fold domain, T. brucei RNA editing ligases contain only the catalytic domain. The OB-fold domain, which is required for interaction with the substrate RNA, is provided in trans by KREPA2 (for TbREL1 and KREPA1 (for TbREL2. KREPA2 enhancement of TbREL1 ligase activity is presumed to occur via an OB-fold-mediated increase in substrate specificity and catalysis. We characterized the interaction between TbREL1 and KREPA2 in vitro using full-length, truncated, and point-mutated ligases. As previously shown, our data indicate strong, specific stimulation of TbREL1 catalytic activity by KREPA2. We narrowed the region of contact to the final 59 C-terminal residues of TbREL1. Specifically, the TbREL1 C-terminal KWKE (441-444 sequence appear to coordinate the KREPA2-mediated enhancement of TbREL1 activities. N-terminal residues F206, T264 and Y275 are crucial for the overall activity of TbREL1, particularly for F206, a mutation of this residue also disrupts KREPA2 interaction. Thus, we have identified the critical TbREL1 regions and amino acids that mediate the KREPA2 interaction.

  8. Trypanosoma brucei brucei: effects of ferrous iron and heme on ecto-nucleoside triphosphate diphosphohydrolase activity.

    Science.gov (United States)

    Leite, Milane S; Thomaz, Rachel; Oliveira, José Henrique M; Oliveira, Pedro L; Meyer-Fernandes, José Roberto

    2009-02-01

    Trypanosoma brucei brucei is the causative agent of animal African trypanosomiasis, also called nagana. Procyclic vector form resides in the midgut of the tsetse fly, which feeds exclusively on blood. Hemoglobin digestion occurs in the midgut resulting in an intense release of free heme. In the present study we show that the magnesium-dependent ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) activity of procyclic T. brucei brucei is inhibited by ferrous iron and heme. The inhibition of E-NTPDase activity by ferrous iron, but not by heme, was prevented by pre-incubation of cells with catalase. However, antioxidants that permeate cells, such as PEG-catalase and N-acetyl-cysteine prevented the inhibition of E-NTPDase by heme. Ferrous iron was able to induce an increase in lipid peroxidation, while heme did not. Therefore, both ferrous iron and heme can inhibit E-NTPDase activity of T. brucei brucei by means of formation of reactive oxygen species, but apparently acting through distinct mechanisms.

  9. The extraordinary mitochondrion and unusual citric acid cycle in Trypanosoma brucei.

    Science.gov (United States)

    van Hellemond, J J; Opperdoes, F R; Tielens, A G M

    2005-11-01

    African trypanosomes are parasitic protozoa that cause sleeping sickness and nagana. Trypanosomes are not only of scientific interest because of their clinical importance, but also because these protozoa contain several very unusual biological features, such as their specially adapted mitochondrion and the compartmentalization of glycolytic enzymes in glycosomes. The energy metabolism of Trypanosoma brucei differs significantly from that of their hosts and changes drastically during the life cycle. Despite the presence of all citric acid cycle enzymes in procyclic insect-stage T. brucei, citric acid cycle activity is not used for energy generation. Recent investigations on the influence of substrate availability on the type of energy metabolism showed that absence of glycolytic substrates did not induce a shift from a fermentative metabolism to complete oxidation of substrates. Apparently, insect-stage T. brucei use parts of the citric acid cycle for other purposes than for complete degradation of mitochondrial substrates. Parts of the cycle are suggested to be used for (i) transport of acetyl-CoA units from the mitochondrion to the cytosol for the biosynthesis of fatty acids, (ii) degradation of proline and glutamate to succinate, (iii) generation of malate, which can then be used for gluconeogenesis. Therefore the citric acid cycle in trypanosomes does not function as a cycle.

  10. 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.

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

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    Matyáš Síma

    2011-06-01

    Full Text Available BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

  12. [Pseudo-tumoral human African trypanosomiasis due to Trypanosoma gambiense. Clinical and tomodensitometry study (author's transl)].

    Science.gov (United States)

    Poisson, M; Bleibel, J M; Regnier, A; Mashaly, R; Le Bigot, P; Danis, M; Buge, A

    The authors report an observation of african trypanosomiasis due to Trypanosoma Gambiense, clinical signs included massive and progressive hemiplegia, papillary edema and vascular shift from median line at arteriography. These pseudo tumoral clinical features are unusual in this disease. Asymetrical heterogenous hypodensities of the centrum semioval are dominant in the initial CT scanner aspect. The confrontation of CT scanner images to the clinical and evolutive data suggests the presence of associated cerebral edema and demyelination. With treatment, hypodensities were regressing while images of subcortical atrophy appeared. Lastly, in spite of severe general signs and the importance of neurological deficit, arsenical treatment associated with high doses of corticotherapy lead to a rapid improvement.

  13. Sleep Sleeping Patch

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The Sleep Sleeping Patch is a new kind of external patch based on modern sleep medicine research achievements, which uses the internationally advanced transdermal therapeutic system (TTS). The Sleep Sleeping Patch transmits natural sleep inducers such as peppermint and liquorice extracts and melatonin through the skin to induce sleep. Clinical research proves that the Sleep Sleeping Patch can effectively improve insomnia and the quality of sleep. Highly effective: With the modern TTS therapy,

  14. Transport proteins determine drug sensitivity and resistance in a protozoan parasite, Trypanosoma brucei

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    Jane Claire Munday

    2015-03-01

    Full Text Available Drug resistance in pathogenic protozoa is very often caused by changes to the ‘transportome’ of the parasites. In Trypanosoma brucei, several transporters have been implicated in uptake of the main classes of drugs, diamidines and melaminophenyl arsenicals. The resistance mechanism had been thought to be due to loss of a transporter known to carry both types of agents: the aminopurine transporter P2, encoded by the gene TbAT1. However, although loss of P2 activity is well-documented as the cause of resistance to the veterinary diamidine diminazene aceturate (Berenil®, cross-resistance between the human-use arsenical melarsoprol and the diamidine pentamidine (MPXR is the result of loss of a separate High Affinity Pentamidine Transporter (HAPT1. A genome-wide RNAi library screen for resistance to pentamidine, published in 2012, gave the key to the genetic identity of HAPT1 by linking the phenomenon to a locus that contains the closely related T. brucei aquaglyceroporin genes TbAQP2 and TbAQP3. Further analysis determined that knockdown of only one pore, TbAQP2, produced the MPXR phenotype. TbAQP2 is an unconventional aquaglyceroporin with unique residues in the selectivity region of the pore, and it was found that in several MPXR lab strains the WT gene was either absent or replaced by a chimeric protein, recombined with parts of TbAQP3. Importantly, wild-type AQP2 was also absent in field isolates of T. b. gambiense, correlating with the outcome of melarsoprol treatment. Expression of a wild-type copy of TbAQP2 in even the most resistant strain completely reversed MPXR and re-introduced HAPT1 function and transport kinetics. Expression of TbAQP2 in Leishmania mexicana introduced a pentamidine transport activity indistinguishable from HAPT1. Although TbAQP2 has been shown to function as a classical aquaglyceroporin it is now clear that it is also a high affinity drug transporter, HAPT1. We discuss here a possible structural rationale for this

  15. Transport proteins determine drug sensitivity and resistance in a protozoan parasite, Trypanosoma brucei

    Science.gov (United States)

    Munday, Jane C.; Settimo, Luca; de Koning, Harry P.

    2015-01-01

    Drug resistance in pathogenic protozoa is very often caused by changes to the ‘transportome’ of the parasites. In Trypanosoma brucei, several transporters have been implicated in uptake of the main classes of drugs, diamidines and melaminophenyl arsenicals. The resistance mechanism had been thought to be due to loss of a transporter known to carry both types of agents: the aminopurine transporter P2, encoded by the gene TbAT1. However, although loss of P2 activity is well-documented as the cause of resistance to the veterinary diamidine diminazene aceturate (DA; Berenil®), cross-resistance between the human-use arsenical melarsoprol and the diamidine pentamidine (melarsoprol/pentamidine cross resistance, MPXR) is the result of loss of a separate high affinity pentamidine transporter (HAPT1). A genome-wide RNAi library screen for resistance to pentamidine, published in 2012, gave the key to the genetic identity of HAPT1 by linking the phenomenon to a locus that contains the closely related T. brucei aquaglyceroporin genes TbAQP2 and TbAQP3. Further analysis determined that knockdown of only one pore, TbAQP2, produced the MPXR phenotype. TbAQP2 is an unconventional aquaglyceroporin with unique residues in the “selectivity region” of the pore, and it was found that in several MPXR lab strains the WT gene was either absent or replaced by a chimeric protein, recombined with parts of TbAQP3. Importantly, wild-type AQP2 was also absent in field isolates of T. b. gambiense, correlating with the outcome of melarsoprol treatment. Expression of a wild-type copy of TbAQP2 in even the most resistant strain completely reversed MPXR and re-introduced HAPT1 function and transport kinetics. Expression of TbAQP2 in Leishmania mexicana introduced a pentamidine transport activity indistinguishable from HAPT1. Although TbAQP2 has been shown to function as a classical aquaglyceroporin it is now clear that it is also a high affinity drug transporter, HAPT1. We discuss here a

  16. 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.

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

    Science.gov (United States)

    Moreno, S Andrea; Nava, Mayerly

    2015-06-01

    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.

  18. Cell-penetrating peptide TP10 shows broad-spectrum activity against both Plasmodium falciparum and Trypanosoma brucei brucei.

    Science.gov (United States)

    Arrighi, Romanico B G; Ebikeme, Charles; Jiang, Yang; Ranford-Cartwright, Lisa; Barrett, Michael P; Langel, Ulo; Faye, Ingrid

    2008-09-01

    Malaria and trypanosomiasis are diseases which afflict millions and for which novel therapies are urgently required. We have tested two well-characterized cell-penetrating peptides (CPPs) for antiparasitic activity. One CPP, designated TP10, has broad-spectrum antiparasitic activity against Plasmodium falciparum, both blood and mosquito stages, and against blood-stage Trypanosoma brucei brucei.

  19. Comparative analysis of the kinomes of three pathogenic trypanosomatids: Leishmania major, Trypanosoma brucei and Trypanosoma cruzi

    OpenAIRE

    Ward Pauline N; Worthey Elizabeth A; Parsons Marilyn; Mottram Jeremy C

    2005-01-01

    Abstract Background The trypanosomatids Leishmania major, Trypanosoma brucei and Trypanosoma cruzi cause some of the most debilitating diseases of humankind: cutaneous leishmaniasis, African sleeping sickness, and Chagas disease. These protozoa possess complex life cycles that involve development in mammalian and insect hosts, and a tightly coordinated cell cycle ensures propagation of the highly polarized cells. However, the ways in which the parasites respond to their environment and coordi...

  20. 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 po

  1. 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.

  2. Proline Metabolism is Essential for Trypanosoma brucei brucei Survival in the Tsetse Vector

    Science.gov (United States)

    Mantilla, Brian S.; Dyer, Naomi A.; Biran, Marc; Bringaud, Frédéric; Lehane, Michael J.; Acosta-Serrano, Alvaro

    2017-01-01

    Adaptation to different nutritional environments is essential for life cycle completion by all Trypanosoma brucei sub-species. In the tsetse fly vector, L-proline is among the most abundant amino acids and is mainly used by the fly for lactation and to fuel flight muscle. The procyclic (insect) stage of T. b. brucei uses L-proline as its main carbon source, relying on an efficient catabolic pathway to convert it to glutamate, and then to succinate, acetate and alanine as the main secreted end products. Here we investigated the essentiality of an undisrupted proline catabolic pathway in T. b. brucei by studying mitochondrial Δ1-pyrroline-5-carboxylate dehydrogenase (TbP5CDH), which catalyzes the irreversible conversion of gamma-glutamate semialdehyde (γGS) into L-glutamate and NADH. In addition, we provided evidence for the absence of a functional proline biosynthetic pathway. TbP5CDH expression is developmentally regulated in the insect stages of the parasite, but absent in bloodstream forms grown in vitro. RNAi down-regulation of TbP5CDH severely affected the growth of procyclic trypanosomes in vitro in the absence of glucose, and altered the metabolic flux when proline was the sole carbon source. Furthermore, TbP5CDH knocked-down cells exhibited alterations in the mitochondrial inner membrane potential (ΔΨm), respiratory control ratio and ATP production. Also, changes in the proline-glutamate oxidative capacity slightly affected the surface expression of the major surface glycoprotein EP-procyclin. In the tsetse, TbP5CDH knocked-down cells were impaired and thus unable to colonize the fly’s midgut, probably due to the lack of glucose between bloodmeals. Altogether, our data show that the regulated expression of the proline metabolism pathway in T. b. brucei allows this parasite to adapt to the nutritional environment of the tsetse midgut. PMID:28114403

  3. Classical clinical signs in rats experimemtally infected with Trypanosoma brucei

    Institute of Scientific and Technical Information of China (English)

    Nwoha Rosemary Ijeoma Ogechi; Omamegbe Joseph Omolathebu

    2015-01-01

    Objective:To investigate clinical signs in Trypanosoma brucei infection in albino rats. Methods:Fourteen rats grouped into 2 with 7 rats in each group were used to determine classical clinical manifestation of Trypanosoma brucei infection in rats. Group A rats were uninfected control and Group B rats were infected with Trypanosoma brucei. Results:Parasitaemia was recorded in Group B by (3.86±0.34) d and the peak of parasitaemia was observed at Day 5 post infection. Classical signs observed included squint eyes, raised whiskers, lethargy, no weight loss, pyrexia, isolation from the other rats, and starry hair coat. Conclusions:These signs could be diagnostic or aid in diagnosis of Trypanosoma brucei infection in rats.

  4. Sleep Quiz

    Science.gov (United States)

    ... suffer from sleep disorders, including sleep apnea, insomnia, narcolepsy, and restless legs syndrome. An untreated sleep disorder ... accidents each year--claiming over 1,500 lives. Narcolepsy is a sleep disorder marked by "sleep attacks." ...

  5. Efficacy and Safety of Pafuramidine versus Pentamidine Maleate for Treatment of First Stage Sleeping Sickness in a Randomized, Comparator-Controlled, International Phase 3 Clinical Trial.

    Directory of Open Access Journals (Sweden)

    Gabriele Pohlig

    2016-02-01

    Full Text Available Sleeping sickness (human African trypanosomiasis [HAT] is a neglected tropical disease with limited treatment options that currently require parenteral administration. In previous studies, orally administered pafuramidine was well tolerated in healthy patients (for up to 21 days and stage 1 HAT patients (for up to 10 days, and demonstrated efficacy comparable to pentamidine.This was a Phase 3, multi-center, randomized, open-label, parallel-group, active control study where 273 male and female patients with first stage Trypanosoma brucei gambiense HAT were treated at six sites: one trypanosomiasis reference center in Angola, one hospital in South Sudan, and four hospitals in the Democratic Republic of the Congo between August 2005 and September 2009 to support the registration of pafuramidine for treatment of first stage HAT in collaboration with the United States Food and Drug Administration. Patients were treated with either 100 mg of pafuramidine orally twice a day for 10 days or 4 mg/kg pentamidine intramuscularly once daily for 7 days to assess the efficacy and safety of pafuramidine versus pentamidine. Pregnant and lactating women as well as adolescents were included. The primary efficacy endpoint was the combined rate of clinical and parasitological cure at 12 months. The primary safety outcome was the frequency and severity of adverse events. The study was registered on the International Clinical Trials Registry Platform at www.clinicaltrials.gov with the number ISRCTN85534673.The overall cure rate at 12 months was 89% in the pafuramidine group and 95% in the pentamidine group; pafuramidine was non-inferior to pentamidine as the upper bound of the 95% confidence interval did not exceed 15%. The safety profile of pafuramidine was superior to pentamidine; however, 3 patients in the pafuramidine group had glomerulonephritis or nephropathy approximately 8 weeks post-treatment. Two of these events were judged as possibly related to

  6. 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.

  7. 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.

  8. 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 - ...

  9. Sleep Problems

    Science.gov (United States)

    ... For Consumers Consumer Information by Audience For Women Sleep Problems Share Tweet Linkedin Pin it More sharing ... PDF 474KB) En Español Medicines to Help You Sleep Tips for Better Sleep Basic Facts about Sleep ...

  10. Nanomolar Inhibitors of Trypanosoma brucei RNA Triphosphatase

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    Paul Smith

    2016-02-01

    Full Text Available Eukaryal taxa differ with respect to the structure and mechanism of the RNA triphosphatase (RTPase component of the mRNA capping apparatus. Protozoa, fungi, and certain DNA viruses have a metal-dependent RTPase that belongs to the triphosphate tunnel metalloenzyme (TTM superfamily. Because the structures, active sites, and chemical mechanisms of the TTM-type RTPases differ from those of mammalian RTPases, the TTM RTPases are potential targets for antiprotozoal, antifungal, and antiviral drug discovery. Here, we employed RNA interference (RNAi knockdown methods to show that Trypanosoma brucei RTPase Cet1 (TbCet1 is necessary for proliferation of procyclic cells in culture. We then conducted a high-throughput biochemical screen for small-molecule inhibitors of the phosphohydrolase activity of TbCet1. We identified several classes of chemicals—including chlorogenic acids, phenolic glycopyranosides, flavonoids, and other phenolics—that inhibit TbCet1 with nanomolar to low-micromolar 50% inhibitory concentrations (IC50s. We confirmed the activity of these compounds, and tested various analogs thereof, by direct manual assays of TbCet1 phosphohydrolase activity. The most potent nanomolar inhibitors included tetracaffeoylquinic acid, 5-galloylgalloylquinic acid, pentagalloylglucose, rosmarinic acid, and miquelianin. TbCet1 inhibitors were less active (or inactive against the orthologous TTM-type RTPases of mimivirus, baculovirus, and budding yeast (Saccharomyces cerevisiae. Our results affirm that a TTM RTPase is subject to potent inhibition by small molecules, with the caveat that parallel screens against TTM RTPases from multiple different pathogens may be required to fully probe the chemical space of TTM inhibition.

  11. Parasite-based screening and proteome profiling reveal orlistat, an FDA-approved drug, as a potential anti Trypanosoma brucei agent.

    Science.gov (United States)

    Yang, Peng-Yu; Wang, Min; Liu, Kai; Ngai, Mun Hong; Sheriff, Omar; Lear, Martin J; Sze, Siu Kwan; He, Cynthia Y; Yao, Shao Q

    2012-07-02

    Trypanosoma brucei is a parasite that causes African sleeping sickness in humans and nagana in livestock and is transmitted by the tsetse fly. There is an urgent need for the development of new drugs against African trypanosomiasis due to the lack of vaccines and effective drugs. Orlistat (also called tetrahydrolipstatin or THL) is an FDA-approved antiobesity drug targeting primarily the pancreatic and gastric lipases within the gastrointestinal tract. It shows potential activities against tumors, mycobacteria, and parasites. Herein, we report the synthesis and evaluation of an expanded set of orlistat-like compounds, some of which showed highly potent trypanocidal activities in both the bloodstream form (BSF) and the procyclic form (PCF) of T. brucei. Subsequent in situ parasite-based proteome profiling was carried out to elucidate potential cellular targets of the drug in both forms. Some newly identified targets were further validated by the labeling of recombinantly expressed enzymes in Escherichia coli lysates. Bioimaging experiments with a selected compound were carried out to study the cellular uptake of the drug in T. brucei. Results indicated that orlistat is much more efficiently taken up by the BSF than the PCF of T. brucei and has clear effects on the morphology of mitochondria, glycosomes, and the endoplasmic reticulum in both BSF and PCF cells. These results support specific effects of orlistat on these organelles and correlate well with our in situ proteome profiling. Given the economic challenges of de novo drug development for neglected diseases, we hope that our findings will stimulate further research towards the conversion of orlistat-like compounds into new trypanocidal drugs.

  12. N-myristoyltransferase inhibitors as new leads to treat sleeping sickness

    Energy Technology Data Exchange (ETDEWEB)

    Frearson, Julie A.; Brand, Stephen; McElroy, Stuart P.; Cleghorn, Laura A.T.; Smid, Ondrej; Stojanovski, Laste; Price, Helen P.; Guther, M. Lucia S.; Torrie, Leah S.; Robinson, David A.; Hallyburton, Irene; Mpamhanga, Chidochangu P.; Brannigan, James A.; Wilkinson, Anthony J.; Hodgkinson, Michael; Hui, Raymond; Qiu, Wei; Raimi, Olawale G.; van Aalten, Daan M.F.; Brenk, Ruth; Gilbert, Ian H.; Read, Kevin D.; Fairlamb, Alan H.; Ferguson, Michael A.J.; Smith, Deborah F.; Wyatt, Paul G. (York); (Toronto); (Dundee)

    2010-11-05

    African sleeping sickness or human African trypanosomiasis, caused by Trypanosoma brucei spp., is responsible for {approx}30,000 deaths each year. Available treatments for this disease are poor, with unacceptable efficacy and safety profiles, particularly in the late stage of the disease when the parasite has infected the central nervous system. Here we report the validation of a molecular target and the discovery of associated lead compounds with the potential to address this lack of suitable treatments. Inhibition of this target - T. brucei N-myristoyltransferase - leads to rapid killing of trypanosomes both in vitro and in vivo and cures trypanosomiasis in mice. These high-affinity inhibitors bind into the peptide substrate pocket of the enzyme and inhibit protein N-myristoylation in trypanosomes. The compounds identified have promising pharmaceutical properties and represent an opportunity to develop oral drugs to treat this devastating disease. Our studies validate T. brucei N-myristoyltransferase as a promising therapeutic target for human African trypanosomiasis.

  13. Crystal structures of Trypanosoma brucei oligopeptidase B broaden the paradigm of catalytic regulation in prolyl oligopeptidase family enzymes.

    Science.gov (United States)

    Canning, Peter; Rea, Dean; Morty, Rory E; Fülöp, Vilmos

    2013-01-01

    Oligopeptidase B cleaves after basic amino acids in peptides up to 30 residues. As a virulence factor in bacteria and trypanosomatid pathogens that is absent in higher eukaryotes, this is a promising drug target. Here we present ligand-free open state and inhibitor-bound closed state crystal structures of oligopeptidase B from Trypanosoma brucei, the causative agent of African sleeping sickness. These (and related) structures show the importance of structural dynamics, governed by a fine enthalpic and entropic balance, in substrate size selectivity and catalysis. Peptides over 30 residues cannot fit the enzyme cavity, preventing the complete domain closure required for a key propeller Asp/Glu to fix the catalytic His and Arg in the catalytically competent conformation. This size exclusion mechanism protects larger peptides and proteins from degradation. Similar bacterial prolyl endopeptidase and archael acylaminoacyl peptidase structures demonstrate this mechanism is conserved among oligopeptidase family enzymes across all three domains of life.

  14. Crystal structures of Trypanosoma brucei oligopeptidase B broaden the paradigm of catalytic regulation in prolyl oligopeptidase family enzymes.

    Directory of Open Access Journals (Sweden)

    Peter Canning

    Full Text Available Oligopeptidase B cleaves after basic amino acids in peptides up to 30 residues. As a virulence factor in bacteria and trypanosomatid pathogens that is absent in higher eukaryotes, this is a promising drug target. Here we present ligand-free open state and inhibitor-bound closed state crystal structures of oligopeptidase B from Trypanosoma brucei, the causative agent of African sleeping sickness. These (and related structures show the importance of structural dynamics, governed by a fine enthalpic and entropic balance, in substrate size selectivity and catalysis. Peptides over 30 residues cannot fit the enzyme cavity, preventing the complete domain closure required for a key propeller Asp/Glu to fix the catalytic His and Arg in the catalytically competent conformation. This size exclusion mechanism protects larger peptides and proteins from degradation. Similar bacterial prolyl endopeptidase and archael acylaminoacyl peptidase structures demonstrate this mechanism is conserved among oligopeptidase family enzymes across all three domains of life.

  15. Sleep Quiz

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Sleep Quiz Past Issues / Summer 2007 Table of Contents ... on. Photo: iStock Take the National Center on Sleep Disorders Research Sleep Quiz TRUE OR FALSE ? _____1. ...

  16. In vitro antitrypanosomal activity of plant terpenes against Trypanosoma brucei.

    Science.gov (United States)

    Otoguro, Kazuhiko; Iwatsuki, Masato; Ishiyama, Aki; Namatame, Miyuki; Nishihara-Tukashima, Aki; Kiyohara, Hiroaki; Hashimoto, Toshihiro; Asakawa, Yoshinori; Omura, Satoshi; Yamada, Haruki

    2011-11-01

    During the course of screening to discover antitrypanosomal compounds, 24 known plant terpenes (6 sesquiterpenes, 14 sesquiterpene lactones and 4 diterpenes) were evaluated for in vitro antitrypanosomal activity against Trypanosoma brucei brucei. Among them, 22 terpenes exhibited antitrypanosomal activity. In particular, α-eudesmol, hinesol, nardosinone and 4-peroxy-1,2,4,5-tetrahydro-α-santonin all exhibited selective and potent antitrypanosomal activities in vitro. Detailed here in an in vitro antitrypanosomal properties and cytotoxicities of the 24 terpenes compared with two therapeutic antitrypanosomal drugs (eflornithine and suramin). This finding represents the first report of promising trypanocidal activity of these terpenes. Present results also provide some valuable insight with regard to structure-activity relationships and the possible mode of action of the compounds.

  17. Fluorinated Sterols Are Suicide Inhibitors of Ergosterol Biosynthesis and Growth in Trypanosoma brucei.

    Science.gov (United States)

    Leaver, David J; Patkar, Presheet; Singha, Ujjal K; Miller, Matthew B; Haubrich, Brad A; Chaudhuri, Minu; Nes, W David

    2015-10-22

    Trypanosoma brucei, the causal agent for sleeping sickness, depends on ergosterol for growth. Here, we describe the effects of a mechanism-based inhibitor, 26-fluorolanosterol (26FL), which converts in vivo to a fluorinated substrate of the sterol C24-methyltransferase essential for sterol methylation and function of ergosterol, and missing from the human host. 26FL showed potent inhibition of ergosterol biosynthesis and growth of procyclic and bloodstream forms while having no effect on cholesterol biosynthesis or growth of human epithelial kidney cells. During exposure of cloned TbSMT to 26-fluorocholesta-5,7,24-trienol, the enzyme is gradually killed as a consequence of the covalent binding of the intermediate C25 cation to the active site (kcat/kinact = 0.26 min(-1)/0.24 min(-1); partition ratio of 1.08), whereas 26FL is non-productively bound. These results demonstrate that poisoning of ergosterol biosynthesis by a 26-fluorinated Δ(24)-sterol is a promising strategy for developing a new treatment for trypanosomiasis.

  18. 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.

  19. Sleep Disorders

    DEFF Research Database (Denmark)

    Rahbek Kornum, Birgitte; Mignot, Emmanuel

    2014-01-01

    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...... 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...

  20. Intraclonal mating occurs during tsetse transmission of Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Ferris Vanessa

    2009-09-01

    Full Text Available Abstract Background Mating in Trypanosoma brucei is a non-obligatory event, triggered by the co-occurrence of different strains in the salivary glands of the vector. Recombinants that result from intra- rather than interclonal mating have been detected, but only in crosses of two different trypanosome strains. This has led to the hypothesis that when trypanosomes recognize a different strain, they release a diffusible factor or pheromone that triggers mating in any cell in the vicinity whether it is of the same or a different strain. This idea assumes that the trypanosome can recognize self and non-self, although there is as yet no evidence for the existence of mating types in T. brucei. Results We investigated intraclonal mating in T. b. brucei by crossing red and green fluorescent lines of a single strain, so that recombinant progeny can be detected in the fly by yellow fluorescence. For strain 1738, seven flies had both red and green trypanosomes in the salivary glands and, in three, yellow trypanosomes were also observed, although they could not be recovered for subsequent analysis. Nonetheless, both red and non-fluorescent clones from these flies had recombinant genotypes as judged by microsatellite and karyotype analyses, and some also had raised DNA contents, suggesting recombination or genome duplication. Strain J10 produced similar results indicative of intraclonal mating. In contrast, trypanosome clones recovered from other flies showed that genotypes can be transmitted with fidelity. When a yellow hybrid clone expressing both red and green fluorescent protein genes was transmitted, the salivary glands contained a mixture of fluorescent-coloured trypanosomes, but only yellow and red clones were recovered. While loss of the GFP gene in the red clones could have resulted from gene conversion, some of these clones showed loss of heterozygosity and raised DNA contents as in the other single strain transmissions. Our observations suggest

  1. In Vitro Trypanocidal Activity of Antibodies to Bacterially Ex­pressed Trypanosoma brucei Tubulin

    Directory of Open Access Journals (Sweden)

    GW Lubega

    2012-09-01

    Full Text Available Background: There are only four drugs for treating African trypanosomiasis, a devastating disease in sub-Saharan Africa. With slow discovery of better drugs, vaccination is viewed as the best method of control. We previously showed that antibodies to native Trypanosoma brucei brucei tubulin inhibit the growth of trypanosomes in culture. Here, we aimed to determine the effect of antibodies to bacte­rially expressed trypanosome tubulin on T. brucei brucei growth. Methods: T. brucei brucei alpha and beta tubulin genes were individually expressed in Escherichia coli under the tryptophan promoter. Monoclonal tubulin antibodies reacted specifically with the ex­pressed tubulins with no cross-reaction with the opposite tubulin. Rabbits were immunized with 450μg each of the concentrated recombinant tubulin, and production of antibodies assessed by ELISA and Western blotting. The effect of polyclonal antibodies on trypanosome growth was deter­mined by culturing bloodstream T. brucei brucei in up to 25% of antisera. Results: Low antisera dilutions (25% from the immunized rabbits inhibited trypanosome growth. The most cytotoxic antisera were from one rabbit immunized with a mixture of both alpha and beta tubulins. However, the result was not reproduced in other rabbits and there was no apparent effect on growth at higher antisera dilutions. Conclusion: Antibodies to bacterially expressed trypanosome tubulin are not effective at killing cul­tured bloodstream trypanosomes.

  2. Population Vulnerability and Disability in Kenya's Tsetse Fly Habitats

    OpenAIRE

    Grady, Sue C.; Messina, Joseph P.; McCord, Paul F.

    2011-01-01

    BACKGROUND: Human African Trypanosomiasis (HAT), also referred to as sleeping sickness, and African Animal Trypanosomaisis (AAT), known as nagana, are highly prevalent parasitic vector-borne diseases in sub-Saharan Africa. Humans acquire trypanosomiasis following the bite of a tsetse fly infected with the protozoa Trypanosoma brucei (T.b.) spp. -i.e., T.b. gambiense in West and Central Africa and T.b. rhodesiense in East and Southern Africa. Over the last decade HAT diagnostic capacity to est...

  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. Structural characterization of CYP51 from Trypanosoma cruzi and Trypanosoma brucei bound to the antifungal drugs posaconazole and fluconazole.

    Directory of Open Access Journals (Sweden)

    Chiung-Kuang Chen

    Full Text Available 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 14alpha-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 A and 2.27 A, and from the related pathogen T. brucei (resolutions of 2.7 A and 2.6 A, 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 degrees 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

  5. Selective inhibition of 6-phosphogluconate dehydrogenase from Trypanosoma brucei

    Science.gov (United States)

    Bertelli, Massimo; El-Bastawissy, Eman; Knaggs, Michael H.; Barrett, Michael P.; Hanau, Stefania; Gilbert, Ian H.

    2001-05-01

    A number of triphenylmethane derivatives have been screened against 6-phosphogluconate dehydrogenase from Trypanosoma brucei and sheep liver. Some of these compounds show good inhibition of the enzymes and also selectivity towards the parasite enzyme. Modelling was undertaken to dock the compounds into the active sites of both enzymes. Using a combination of DOCK 3.5 and FLEXIDOCK a correlation was obtained between docking score and both activity for the enzymes and selectivity. Visualisation of the docked structures of the inhibitors in the active sites of the enzymes yielded a possible explanation of the selectivity for the parasite enzyme.

  6. Healthy Sleep Habits

    Science.gov (United States)

    ... Sleep Apnea Testing CPAP Healthy Sleep Habits Healthy Sleep Habits Your behaviors during the day, and especially ... team at an AASM accredited sleep center . Quick Sleep Tips Follow these tips to establish healthy sleep ...

  7. What Are Sleep Studies?

    Science.gov (United States)

    ... Share this page from the NHLBI on Twitter. Sleep Studies Also known as polysomnography. Sleep studies are ... Sleep Rate This Content: Updated: December 9, 2016 Sleep Infographic Sleep Disorders & Insufficient Sleep: Improving Health through ...

  8. 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.

  9. 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 ...

  10. 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.

  11. Loop-mediated isothermal amplification (LAMP method for rapid detection of Trypanosoma brucei rhodesiense.

    Directory of Open Access Journals (Sweden)

    Zablon Kithinji Njiru

    Full Text Available Loop-mediated isothermal amplification (LAMP of DNA is a novel technique that rapidly amplifies target DNA under isothermal conditions. In the present study, a LAMP test was designed from the serum resistance-associated (SRA gene of Trypanosoma brucei rhodesiense, the cause of the acute form of African sleeping sickness, and used to detect parasite DNA from processed and heat-treated infected blood samples. The SRA gene is specific to T. b. rhodesiense and has been shown to confer resistance to lysis by normal human serum. The assay was performed at 62 degrees C for 1 h, using six primers that recognised eight targets. The template was varying concentrations of trypanosome DNA and supernatant from heat-treated infected blood samples. The resulting amplicons were detected using SYTO-9 fluorescence dye in a real-time thermocycler, visual observation after the addition of SYBR Green I, and gel electrophoresis. DNA amplification was detected within 35 min. The SRA LAMP test had an unequivocal detection limit of one pg of purified DNA (equivalent to 10 trypanosomes/ml and 0.1 pg (1 trypanosome/ml using heat-treated buffy coat, while the detection limit for conventional SRA PCR was approximately 1,000 trypanosomes/ml. The expected LAMP amplicon was confirmed through restriction enzyme RsaI digestion, identical melt curves, and sequence analysis. The reproducibility of the SRA LAMP assay using water bath and heat-processed template, and the ease in results readout show great potential for the diagnosis of T. b. rhodesiense in endemic regions.

  12. 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.

  13. Cofactor-independent phosphoglycerate mutase is an essential gene in procyclic form Trypanosoma brucei.

    Science.gov (United States)

    Djikeng, Appolinaire; Raverdy, Sylvine; Foster, Jeremy; Bartholomeu, Daniella; Zhang, Yinhua; El-Sayed, Najib M; Carlow, Clotilde

    2007-03-01

    Glycolysis and gluconeogenesis are, in part, driven by the interconversion of 3- and 2-phosphoglycerate (3-PG and 2-PG) which is performed by phosphoglycerate mutases (PGAMs) which can be cofactor dependant (dPGAM) or cofactor independent (iPGAM). The African trypanosome, Trypanosoma brucei, possesses the iPGAM form which is thought to play an important role in glycolysis. Here, we report on the use of RNA interference to down-regulate the T. brucei iPGAM in procyclic form T. brucei and evaluation of the resulting phenotype. We first demonstrated biochemically that depletion of the steady state levels of iPGM mRNA correlates with a marked reduction of enzyme activity. We further show that iPGAM is required for cell growth in procyclic T. brucei.

  14. Eleganolone, a Diterpene from the French Marine Alga Bifurcaria bifurcata Inhibits Growth of the Human Pathogens Trypanosoma brucei and Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Anne-Marie Rusig

    2013-02-01

    Full Text Available Organic extracts of 20 species of French seaweed have been screened against Trypanosoma brucei rhodesiense trypomastigotes, the parasite responsible for sleeping sickness. These extracts have previously shown potent antiprotozoal activities in vitro against Plasmodium falciparum and Leishmania donovani. The selectivity of the extracts was also evaluated by testing cytotoxicity on a mammalian L6 cell line. The ethyl acetate extract of the brown seaweed, Bifurcaria bifurcata, showed strong trypanocidal activity with a mild selectivity index (IC50 = 0.53 µg/mL; selectivity index (SI = 11.6. Bio-guided fractionation led to the isolation of eleganolone, the main diterpenoid isolated from this species. Eleganolone contributes only mildly to the trypanocidal activity of the ethyl acetate extract (IC50 = 45.0 µM, SI = 4.0. However, a selective activity against P. falciparum erythrocytic stages in vitro has been highlighted (IC50 = 7.9 µM, SI = 21.6.

  15. Eleganolone, a Diterpene from the French Marine Alga Bifurcaria bifurcata Inhibits Growth of the Human Pathogens Trypanosoma brucei and Plasmodium falciparum

    Science.gov (United States)

    Gallé, Jean-Baptiste; Attioua, Barthélémy; Kaiser, Marcel; Rusig, Anne-Marie; Lobstein, Annelise; Vonthron-Sénécheau, Catherine

    2013-01-01

    Organic extracts of 20 species of French seaweed have been screened against Trypanosoma brucei rhodesiense trypomastigotes, the parasite responsible for sleeping sickness. These extracts have previously shown potent antiprotozoal activities in vitro against Plasmodium falciparum and Leishmania donovani. The selectivity of the extracts was also evaluated by testing cytotoxicity on a mammalian L6 cell line. The ethyl acetate extract of the brown seaweed, Bifurcaria bifurcata, showed strong trypanocidal activity with a mild selectivity index (IC50 = 0.53 µg/mL; selectivity index (SI) = 11.6). Bio-guided fractionation led to the isolation of eleganolone, the main diterpenoid isolated from this species. Eleganolone contributes only mildly to the trypanocidal activity of the ethyl acetate extract (IC50 = 45.0 µM, SI = 4.0). However, a selective activity against P. falciparum erythrocytic stages in vitro has been highlighted (IC50 = 7.9 µM, SI = 21.6). PMID:23442789

  16. Total sleep deprivation, chronic sleep restriction and sleep disruption.

    Science.gov (United States)

    Reynolds, Amy C; Banks, Siobhan

    2010-01-01

    Sleep loss may result from total sleep deprivation (such as a shift worker might experience), chronic sleep restriction (due to work, medical conditions or lifestyle) or sleep disruption (which is common in sleep disorders such as sleep apnea or restless legs syndrome). Total sleep deprivation has been widely researched, and its effects have been well described. Chronic sleep restriction and sleep disruption (also known as sleep fragmentation) have received less experimental attention. Recently, there has been increasing interest in sleep restriction and disruption as it has been recognized that they have a similar impact on cognitive functioning as a period of total sleep deprivation. Sleep loss causes impairments in cognitive performance and simulated driving and induces sleepiness, fatigue and mood changes. This review examines recent research on the effects of sleep deprivation, restriction and disruption on cognition and neurophysiologic functioning in healthy adults, and contrasts the similarities and differences between these three modalities of sleep loss.

  17. 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.

  18. Mosaic VSGs and the scale of Trypanosoma brucei antigenic variation.

    Directory of Open Access Journals (Sweden)

    James P J Hall

    Full Text Available A main determinant of prolonged Trypanosoma brucei infection and transmission and success of the parasite is the interplay between host acquired immunity and antigenic variation of the parasite variant surface glycoprotein (VSG coat. About 0.1% of trypanosome divisions produce a switch to a different VSG through differential expression of an archive of hundreds of silent VSG genes and pseudogenes, but the patterns and extent of the trypanosome diversity phenotype, particularly in chronic infection, are unclear. We applied longitudinal VSG cDNA sequencing to estimate variant richness and test whether pseudogenes contribute to antigenic variation. We show that individual growth peaks can contain at least 15 distinct variants, are estimated computationally to comprise many more, and that antigenically distinct 'mosaic' VSGs arise from segmental gene conversion between donor VSG genes or pseudogenes. The potential for trypanosome antigenic variation is probably much greater than VSG archive size; mosaic VSGs are core to antigenic variation and chronic infection.

  19. Pathogenesis of anemia in Trypanosoma brucei-infected mice.

    Science.gov (United States)

    Amole, B O; Clarkson, A B; Shear, H L

    1982-01-01

    The pathogenesis of anemia was studied in trypanosome-infected mice. A strain of Trypanosoma brucei, TREU 667, was used which first produces an acute phase marked by waves of parasitemia. Erythrocytes from infected animals were coated with immunoglobulin M during or just before the waves of anemia and parasitological crises. Erythrocytes from normal animals could be sensitized with "precrisis" sera presumably containing antigen and antibody. These data suggest that anemia during the acute phase is due to sensitization of erythrocytes with immunoglobulin M-antigen complexes. The anemia is partially compensated by a strong erythropoietic response. The acute phase is followed by a chronic phase marked by a constant high parasitemia and immunosuppression. The less marked anemia occurring during this latter phase is due to hemodilution and perhaps a low but significant immune response to the parasites, which causes continuing erythrocyte sensitization by immunoglobulin M-antigen complexes. PMID:7201455

  20. Trypanosoma brucei: a putative RNA polymerase II promoter.

    Science.gov (United States)

    Bayele, Henry K

    2009-12-01

    RNA polymerase II (pol II) promoters are rare in the African trypanosome Trypanosoma brucei because gene regulation in the parasite is complex and polycistronic. Here, we describe a putative pol II promoter and its structure-function relationship. The promoter has features of an archetypal eukaryotic pol II promoter including putative canonical CCAAT and TATA boxes, and an initiator element. However, the spatial arrangement of these elements is only similar to yeast pol II promoters. Deletion mapping and transcription assays enabled delineation of a minimal promoter that could drive orientation-independent reporter gene expression suggesting that it may be a bidirectional promoter. In vitro transcription in a heterologous nuclear extract revealed that the promoter can be recognized by the basal eukaryotic transcription complex. This suggests that the transcription machinery in the parasite may be very similar to those of other eukaryotes.

  1. Sleep and Women

    Science.gov (United States)

    ... hygiene sleep length Sleep Movement Disorders Sleep Need Sleep talking Sleeping Pills sleepwalking Snoring stress Stroke Suicide Supplements surgery Technology Teens Telemedicine television The internet Time change Transportation trauma travel Treatments ...

  2. 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 ( ...

  3. American Sleep Association

    Science.gov (United States)

    ... Sleep Disorders Book Join ASA Press Room American Sleep Association Improving public health by increasing awareness about ... Members Username or Email Password Remember Me Register Sleep Blog Changing Bad Sleep Habits Asthma and Sleep ...

  4. Sleep and Chronic Disease

    Science.gov (United States)

    ... message, please visit this page: About CDC.gov . Sleep About Us About Sleep Key Sleep Disorders Sleep ... Sheets Data & Statistics Projects and Partners Resources Events Sleep and Chronic Disease Recommend on Facebook Tweet Share ...

  5. Sleep Disturbances

    Science.gov (United States)

    ... get up in the middle of the night. Sleep in a cool dark place and use the bed only for sleeping and sexual activity. Do not read or watch television in bed. Avoid “screen time” — television, phones, tablets ...

  6. Ancestral sleep.

    Science.gov (United States)

    de la Iglesia, Horacio O; Moreno, Claudia; Lowden, Arne; Louzada, Fernando; Marqueze, Elaine; Levandovski, Rosa; Pilz, Luisa K; Valeggia, Claudia; Fernandez-Duque, Eduardo; Golombek, Diego A; Czeisler, Charles A; Skene, Debra J; Duffy, Jeanne F; Roenneberg, Till

    2016-04-01

    While we do not yet understand all the functions of sleep, its critical role for normal physiology and behaviour is evident. Its amount and temporal pattern depend on species and condition. Humans sleep about a third of the day with the longest, consolidated episode during the night. The change in lifestyle from hunter-gatherers via agricultural communities to densely populated industrialized centres has certainly affected sleep, and a major concern in the medical community is the impact of insufficient sleep on health [1,2]. One of the causal mechanisms leading to insufficient sleep is altered exposure to the natural light-dark cycle. This includes the wide availability of electric light, attenuated exposure to daylight within buildings, and evening use of light-emitting devices, all of which decrease the strength of natural light-dark signals that entrain circadian systems [3].

  7. 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 ...

  8. MIF Contributes to Trypanosoma brucei Associated Immunopathogenicity Development

    Science.gov (United States)

    Stijlemans, Benoît; Leng, Lin; Brys, Lea; Sparkes, Amanda; Vansintjan, Liese; Caljon, Guy; Raes, Geert; Van Den Abbeele, Jan; Van Ginderachter, Jo A.; Beschin, Alain

    2014-01-01

    African trypanosomiasis is a chronic debilitating disease affecting the health and economic well-being of many people in developing countries. The pathogenicity associated with this disease involves a persistent inflammatory response, whereby M1-type myeloid cells, including Ly6Chigh inflammatory monocytes, are centrally implicated. A comparative gene analysis between trypanosusceptible and trypanotolerant animals identified MIF (macrophage migrating inhibitory factor) as an important pathogenic candidate molecule. Using MIF-deficient mice and anti-MIF antibody treated mice, we show that MIF mediates the pathogenic inflammatory immune response and increases the recruitment of inflammatory monocytes and neutrophils to contribute to liver injury in Trypanosoma brucei infected mice. Moreover, neutrophil-derived MIF contributed more significantly than monocyte-derived MIF to increased pathogenic liver TNF production and liver injury during trypanosome infection. MIF deficient animals also featured limited anemia, coinciding with increased iron bio-availability, improved erythropoiesis and reduced RBC clearance during the chronic phase of infection. Our data suggest that MIF promotes the most prominent pathological features of experimental trypanosome infections (i.e. anemia and liver injury), and prompt considering MIF as a novel target for treatment of trypanosomiasis-associated immunopathogenicity. PMID:25255103

  9. MIF contributes to Trypanosoma brucei associated immunopathogenicity development.

    Directory of Open Access Journals (Sweden)

    Benoît Stijlemans

    2014-09-01

    Full Text Available African trypanosomiasis is a chronic debilitating disease affecting the health and economic well-being of many people in developing countries. The pathogenicity associated with this disease involves a persistent inflammatory response, whereby M1-type myeloid cells, including Ly6C(high inflammatory monocytes, are centrally implicated. A comparative gene analysis between trypanosusceptible and trypanotolerant animals identified MIF (macrophage migrating inhibitory factor as an important pathogenic candidate molecule. Using MIF-deficient mice and anti-MIF antibody treated mice, we show that MIF mediates the pathogenic inflammatory immune response and increases the recruitment of inflammatory monocytes and neutrophils to contribute to liver injury in Trypanosoma brucei infected mice. Moreover, neutrophil-derived MIF contributed more significantly than monocyte-derived MIF to increased pathogenic liver TNF production and liver injury during trypanosome infection. MIF deficient animals also featured limited anemia, coinciding with increased iron bio-availability, improved erythropoiesis and reduced RBC clearance during the chronic phase of infection. Our data suggest that MIF promotes the most prominent pathological features of experimental trypanosome infections (i.e. anemia and liver injury, and prompt considering MIF as a novel target for treatment of trypanosomiasis-associated immunopathogenicity.

  10. Exosome secretion affects social motility in Trypanosoma brucei

    Science.gov (United States)

    Shaked, Hadassa; Arvatz, Gil; Tkacz, Itai Dov; Binder, Lior; Waldman Ben-Asher, Hiba; Okalang, Uthman; Chikne, Vaibhav; Cohen-Chalamish, Smadar; Michaeli, Shulamit

    2017-01-01

    Extracellular vesicles (EV) secreted by pathogens function in a variety of biological processes. Here, we demonstrate that in the protozoan parasite Trypanosoma brucei, exosome secretion is induced by stress that affects trans-splicing. Following perturbations in biogenesis of spliced leader RNA, which donates its spliced leader (SL) exon to all mRNAs, or after heat-shock, the SL RNA is exported to the cytoplasm and forms distinct granules, which are then secreted by exosomes. The exosomes are formed in multivesicular bodies (MVB) utilizing the endosomal sorting complexes required for transport (ESCRT), through a mechanism similar to microRNA secretion in mammalian cells. Silencing of the ESCRT factor, Vps36, compromised exosome secretion but not the secretion of vesicles derived from nanotubes. The exosomes enter recipient trypanosome cells. Time-lapse microscopy demonstrated that cells secreting exosomes or purified intact exosomes affect social motility (SoMo). This study demonstrates that exosomes are delivered to trypanosome cells and can change their migration. Exosomes are used to transmit stress signals for communication between parasites. PMID:28257521

  11. Proteins associated with SF3a60 in T. brucei.

    Directory of Open Access Journals (Sweden)

    Benson Nyambega

    Full Text Available Trypanosoma brucei relies on Spliced leader trans splicing to generate functional messenger RNAs. Trans splicing joins the specialized SL exon from the SL RNA to pre-mRNAs and is mediated by the trans-spliceosome, which is made up of small nuclear ribonucleoprotein particles and non-snRNP factors. Although the trans spliceosome is essential for trypanosomatid gene expression, not all spliceosomal protein factors are known and of these, only a few are completely characterized. In this study, we have characterized the trypanosome Splicing Factor, SF3a60, the only currently annotated SF3a component. As expected, epitope-tagged SF3a60 localizes in the trypanosome nucleus. SF3a60 is essential for cell viability but its depletion seem to have no detectable effect on trans-splicing. In addition, we used SF3a60 as bait in a Yeast-2-hybrid system screen and identified its interacting protein factors. The interactions with SF3a120, SF3a66 and SAP130 were confirmed by tandem affinity purification and mass spectrometry.

  12. Proteomics and the Trypanosoma brucei cytoskeleton: advances and opportunities.

    Science.gov (United States)

    Portman, Neil; Gull, Keith

    2012-08-01

    Trypanosoma brucei is the etiological agent of devastating parasitic disease in humans and livestock in sub-saharan Africa. The pathogenicity and growth of the parasite are intimately linked to its shape and form. This is in turn derived from a highly ordered microtubule cytoskeleton that forms a tightly arrayed cage directly beneath the pellicular membrane and numerous other cytoskeletal structures such as the flagellum. The parasite undergoes extreme changes in cellular morphology during its life cycle and cell cycles which require a high level of integration and coordination of cytoskeletal processes. In this review we will discuss the role that proteomics techniques have had in advancing our understanding of the molecular composition of the cytoskeleton and its functions. We then consider future opportunities for the application of these techniques in terms of addressing some of the unanswered questions of trypanosome cytoskeletal cell biology with particular focus on the differences in the composition and organisation of the cytoskeleton through the trypanosome life-cycle.

  13. Problems sleeping during pregnancy

    Science.gov (United States)

    ... sleeping References Balserak BI, Lee KA. Sleep and sleep disorders associated with pregnancy. In: Kryger M, Roth T, ... Elsevier; 2017:chap 156. Ibrahim S, Foldvary-Shaefer N. Sleep disorders in pregnancy: implications, evaluation, and treatment. Neurologic Clinics . ...

  14. Sleep Terrors (Night Terrors)

    Science.gov (United States)

    ... sleepwalking. Like sleepwalking, sleep terrors are considered a parasomnia — an undesired occurrence during sleep. Although sleep terrors are more common in children, they can also affect adults. A sleep terror ...

  15. American Sleep Apnea Association

    Science.gov (United States)

    American Sleep Apnea Association Learn About the CPAP Assistance Program About ASAA News about ASAA Who we are Leadership Team Supporting the ASAA Financials Learn Healthy sleep Sleep apnea Other sleep disorders Personal stories Treat Test Yourself ...

  16. 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 ...

  17. Sleep and Aging

    Science.gov (United States)

    ... version of this page please turn Javascript on. Sleep and Aging About Sleep We all look forward to a good night's ... health and quality of life. Two Types of Sleep There are two types of sleep: non-rapid ...

  18. 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 ...

  19. Sleep Apnea (For Parents)

    Science.gov (United States)

    ... Feeding Your 1- to 2-Year-Old 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 ...

  20. A trans-spliced telomerase RNA dictates telomere synthesis in Trypanosoma brucei

    Institute of Scientific and Technical Information of China (English)

    Ranjodh Sandhu; Samantha Sanford; Shrabani Basu; MinA Park; Unnati M Pandya; Bibo Li; Kausik Chakrabarti

    2013-01-01

    Telomerase is a ribonucleoprotein enzyme typically required for sustained cell proliferation.Although both telomerase activity and the telomerase catalytic protein component,TbTERT,have been identified in the eukaryotic pathogen Trypanosoma brucei,the RNA molecule that dictates telomere synthesis remains unknown.Here,we identify the RNA component of Trypanosoma brucei telomerase,TbTR,and provide phylogenetic and in vivo evidence for TbTR's native folding and activity.We show that TbTR is processed through trans-splicing,and is a capped transcript that interacts and copurifies with TbTERT in vivo.Deletion of TbTR caused progressive shortening of telomeres at a rate of 3-5 bp/population doubling (PD),which can be rescued by ectopic expression of a wild-type allele of TbTR in an apparent dose-dependent manner.Remarkably,introduction of mutations in the TbTR template domain resulted in corresponding mutant telomere sequences,demonstrating that telomere synthesis in T.brucei is dependent on TbTR.We also propose a secondary structure model for TbTR based on phylogenetic analysis and chemical probing experiments,thus defining TbTR domains that may have important functional implications in telomere synthesis.Identification and characterization of TbTR not only provide important insights into T.brucei telomere functions,which have been shown to play important roles in T.brucei pathogenesis,but also offer T.brucei as an attractive model system for studying telomerase biology in pathogenic protozoa and for comparative analysis of telomerase function with higher eukaryotes.

  1. Sleep aspnea

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008057 A multi-center study on the association between sleep apnea and prevalence of hypertension. CHEN Baoyuan(陈宝元), et al. Dept Respir Med, Tianjin Med Univ General Hosp, Tianjin 300052. Chin J Tuberc Respir Dis, 2007;30(12):894-897. Objective To investigate the prevalence of hypertension among sleep apnea patients and the associated factors. Methods A total of 2297 patients (male 1310, female 211) from 20 teaching hospita

  2. 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 ... simply worn out? Perhaps the solution is better sleep. Think about all the factors that can interfere ...

  3. Adaptation of Trypanosoma rhodesiense to hypohaptoglobinaemic serum requires transcription of the APOL1 resistance gene in a RNA polymerase I locus.

    Science.gov (United States)

    Lecordier, Laurence; Uzureau, Pierrick; Tebabi, Patricia; Brauner, Jonathan; Benghiat, Fleur Samantha; Vanhollebeke, Benoit; Pays, Etienne

    2015-08-01

    Human apolipoprotein L1 (APOL1) kills African trypanosomes except Trypanosoma rhodesiense and Trypanosoma gambiense, the parasites causing sleeping sickness. APOL1 uptake into trypanosomes is favoured by its association with the haptoglobin-related protein-haemoglobin complex, which binds to the parasite surface receptor for haptoglobin-haemoglobin. As haptoglobin-haemoglobin can saturate the receptor, APOL1 uptake is increased in haptoglobin-poor (hypohaptoglobinaemic) serum (HyHS). While T. rhodesiense resists APOL1 by RNA polymerase I (pol-I)-mediated expression of the serum resistance-associated (SRA) protein, T. gambiense resists by pol-II-mediated expression of the T. gambiense-specific glycoprotein (TgsGP). Moreover, in T. gambiense resistance to HyHS is linked to haptoglobin-haemoglobin receptor inactivation by mutation. We report that unlike T. gambiense, T. rhodesiense possesses a functional haptoglobin-haemoglobin receptor, and that like T. gambiense experimentally provided with active receptor, this parasite is killed in HyHS because of receptor-mediated APOL1 uptake. However, T. rhodesiense could adapt to low haptoglobin by increasing transcription of SRA. When assayed in Trypanosoma brucei, resistance to HyHS occurred with pol-I-, but not with pol-II-mediated SRA expression. Similarly, T. gambiense provided with active receptor acquired resistance to HyHS only when TgsGP was moved to a pol-I locus. Thus, transcription by pol-I favours adaptive gene regulation, explaining the presence of SRA in a pol-I locus.

  4. Cytosolic NADPH homeostasis in glucose-starved procyclic Trypanosoma brucei relies on malic enzyme and the pentose phosphate pathway fed by gluconeogenic flux.

    Science.gov (United States)

    Allmann, Stefan; Morand, Pauline; Ebikeme, Charles; Gales, Lara; Biran, Marc; Hubert, Jane; Brennand, Ana; Mazet, Muriel; Franconi, Jean-Michel; Michels, Paul A M; Portais, Jean-Charles; Boshart, Michael; Bringaud, Frédéric

    2013-06-21

    All living organisms depend on NADPH production to feed essential biosyntheses and for oxidative stress defense. Protozoan parasites such as the sleeping sickness pathogen Trypanosoma brucei adapt to different host environments, carbon sources, and oxidative stresses during their infectious life cycle. The procyclic stage develops in the midgut of the tsetse insect vector, where they rely on proline as carbon source, although they prefer glucose when grown in rich media. Here, we investigate the flexible and carbon source-dependent use of NADPH synthesis pathways in the cytosol of the procyclic stage. The T. brucei genome encodes two cytosolic NADPH-producing pathways, the pentose phosphate pathway (PPP) and the NADP-dependent malic enzyme (MEc). Reverse genetic blocking of those pathways and a specific inhibitor (dehydroepiandrosterone) of glucose-6-phosphate dehydrogenase together established redundancy with respect to H2O2 stress management and parasite growth. Blocking both pathways resulted in ∼10-fold increase of susceptibility to H2O2 stress and cell death. Unexpectedly, the same pathway redundancy was observed in glucose-rich and glucose-depleted conditions, suggesting that gluconeogenesis can feed the PPP to provide NADPH. This was confirmed by (i) a lethal phenotype of RNAi-mediated depletion of glucose-6-phosphate isomerase (PGI) in the glucose-depleted Δmec/Δmec null background, (ii) an ∼10-fold increase of susceptibility to H2O2 stress observed for the Δmec/Δmec/(RNAi)PGI double mutant when compared with the single mutants, and (iii) the (13)C enrichment of glycolytic and PPP intermediates from cells incubated with [U-(13)C]proline, in the absence of glucose. Gluconeogenesis-supported NADPH supply may also be important for nucleotide and glycoconjugate syntheses in the insect host.

  5. The cell cycle regulated transcriptome of Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Stuart K Archer

    Full Text Available Progression of the eukaryotic cell cycle requires the regulation of hundreds of genes to ensure that they are expressed at the required times. Integral to cell cycle progression in yeast and animal cells are temporally controlled, progressive waves of transcription mediated by cell cycle-regulated transcription factors. However, in the kinetoplastids, a group of early-branching eukaryotes including many important pathogens, transcriptional regulation is almost completely absent, raising questions about the extent of cell-cycle regulation in these organisms and the mechanisms whereby regulation is achieved. Here, we analyse gene expression over the Trypanosoma brucei cell cycle, measuring changes in mRNA abundance on a transcriptome-wide scale. We developed a "double-cut" elutriation procedure to select unperturbed, highly synchronous cell populations from log-phase cultures, and compared this to synchronization by starvation. Transcriptome profiling over the cell cycle revealed the regulation of at least 430 genes. While only a minority were homologous to known cell cycle regulated transcripts in yeast or human, their functions correlated with the cellular processes occurring at the time of peak expression. We searched for potential target sites of RNA-binding proteins in these transcripts, which might earmark them for selective degradation or stabilization. Over-represented sequence motifs were found in several co-regulated transcript groups and were conserved in other kinetoplastids. Furthermore, we found evidence for cell-cycle regulation of a flagellar protein regulon with a highly conserved sequence motif, bearing similarity to consensus PUF-protein binding motifs. RNA sequence motifs that are functional in cell-cycle regulation were more widespread than previously expected and conserved within kinetoplastids. These findings highlight the central importance of post-transcriptional regulation in the proliferation of parasitic kinetoplastids.

  6. 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 Trypanosomiasi

  7. 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 cod

  8. Dynamic Modelling under Uncertainty : The Case of Trypanosoma brucei Energy Metabolism

    NARCIS (Netherlands)

    Achcar, Fiona; Kerkhoven, Eduard J.; Bakker, Barbara M.; Barrett, Michael P.; Breitling, Rainer; Papin, Jason A.

    2012-01-01

    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 metabol

  9. Handling Uncertainty in Dynamic Models : The Pentose Phosphate Pathway in Trypanosoma brucei

    NARCIS (Netherlands)

    Kerkhoven, Eduard J.; Achcar, Fiona; Alibu, Vincent P.; Burchmore, Richard J.; Gilbert, Ian H.; Trybilo, Maciej; Driessen, Nicole N.; Gilbert, David; Breitling, Rainer; Bakker, Barbara M.; Barrett, Michael P.

    2013-01-01

    Dynamic models of metabolism can be useful in identifying potential drug targets, especially in unicellular organisms. A model of glycolysis in the causative agent of human African trypanosomiasis, Trypanosoma brucei, has already shown the utility of this approach. Here we add the pentose phosphate

  10. Involvement of lysosomes in the uptake of macromolecular material by bloodstream forms of Trypanosoma brucei.

    Science.gov (United States)

    Opperdoes, F R; Van Roy, J

    1982-09-01

    To investigate whether the lysosomes of Trypanosoma brucei are capable of uptake of macromolecules after internalization by the cell, we used Triton WR-1339, a non-digestible macromolecular compound, which is known to cause a marked decrease in the density of hepatic lysosomes due to massive intralysosomal storage. Intraperitoneal administration of 0.4 g/kg Triton WR-1339 to rats infected with T. brucei led to the development of a large vacuole in the trypanosomes between nucleus and kinetoplast within 22 h. Higher doses (2 g/kg) led to the disappearance of the trypanosomes from the blood and resulted in permanent cures (greater than 100 days). Lysosomes isolated from the trypanosomes of animals treated with a sub-curative dose showed a decrease in equilibrium density of 0.03 g/cm3 in sucrose gradients. These lysosomes were partly damaged as evidenced by a reduction in latency and an increase in the non-sedimentable part of lysosomal enzymes. We conclude that acid proteinase and alpha-mannosidase-containing organelles of T. brucei take up exogenous macromolecules and must therefore be considered as true lysosomes and that Triton WR-1339 acts in T. brucei as a true lysosomotropic drug. Its trypanocidal action probably results from an interference with lysosomal function.

  11. Telomere length affects the frequency and mechanism of antigenic variation in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Galadriel A Hovel-Miner

    Full Text Available Trypanosoma brucei is a master of antigenic variation and immune response evasion. Utilizing a genomic repertoire of more than 1000 Variant Surface Glycoprotein-encoding genes (VSGs, T. brucei can change its protein coat by "switching" from the expression of one VSG to another. Each active VSG is monoallelically expressed from only one of approximately 15 subtelomeric sites. Switching VSG expression occurs by three predominant mechanisms, arguably the most significant of which is the non-reciprocal exchange of VSG containing DNA by duplicative gene conversion (GC. How T. brucei orchestrates its complex switching mechanisms remains to be elucidated. Recent work has demonstrated that an exogenous DNA break in the active site could initiate a GC based switch, yet the source of the switch-initiating DNA lesion under natural conditions is still unknown. Here we investigated the hypothesis that telomere length directly affects VSG switching. We demonstrate that telomerase deficient strains with short telomeres switch more frequently than genetically identical strains with long telomeres and that, when the telomere is short, switching preferentially occurs by GC. Our data supports the hypothesis that a short telomere at the active VSG expression site results in an increase in subtelomeric DNA breaks, which can initiate GC based switching. In addition to their significance for T. brucei and telomere biology, the findings presented here have implications for the many diverse pathogens that organize their antigenic genes in subtelomeric regions.

  12. Nucleic acid sequence-based amplification with oligochromatography for detection of Trypanosoma brucei in clinical samples

    NARCIS (Netherlands)

    C.M. Mugasa; T. Laurent; G.J. Schoone; P.A. Kager; G.W. Lubega; H.D.F.H. Schallig

    2009-01-01

    Molecular tools, such as real-time nucleic acid sequence-based amplification (NASBA) and PCR, have been developed to detect Trypanosoma brucei parasites in blood for the diagnosis of human African trypanosomiasis (HAT). Despite good sensitivity, these techniques are not implemented in HAT control pr

  13. The major transcripts of the kinetoplast Trypanosoma brucei are very small ribosomal RNA's.

    NARCIS (Netherlands)

    I.C. Eperon; J.W.G. Janssen; J.H.J. Hoeijmakers (Jan); P. Borst (Piet)

    1983-01-01

    textabstractThe nucleotide sequence has been determined of a 2.2 kb segment of kinetoplast DNA, which encodes the major mitochondrial transcripts (12S and 9S) of Trypanosoma brucei. The sequence shows that the 12S RNA is a large subunit rRNA, although sufficiently unusual for resistance to chloramph

  14. 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

  15. Neuroimmunologic aspects of sleep and sleep loss

    Science.gov (United States)

    Rogers, N. L.; Szuba, M. P.; Staab, J. P.; Evans, D. L.; Dinges, D. F.

    2001-01-01

    The complex and intimate interactions between the sleep and immune systems have been the focus of study for several years. Immune factors, particularly the interleukins, regulate sleep and in turn are altered by sleep and sleep deprivation. The sleep-wake cycle likewise regulates normal functioning of the immune system. Although a large number of studies have focused on the relationship between the immune system and sleep, relatively few studies have examined the effects of sleep deprivation on immune parameters. Studies of sleep deprivation's effects are important for several reasons. First, in the 21st century, various societal pressures require humans to work longer and sleep less. Sleep deprivation is becoming an occupational hazard in many industries. Second, to garner a greater understanding of the regulatory effects of sleep on the immune system, one must understand the consequences of sleep deprivation on the immune system. Significant detrimental effects on immune functioning can be seen after a few days of total sleep deprivation or even several days of partial sleep deprivation. Interestingly, not all of the changes in immune physiology that occur as a result of sleep deprivation appear to be negative. Numerous medical disorders involving the immune system are associated with changes in the sleep-wake physiology--either being caused by sleep dysfunction or being exacerbated by sleep disruption. These disorders include infectious diseases, fibromyalgia, cancers, and major depressive disorder. In this article, we will describe the relationships between sleep physiology and the immune system, in states of health and disease. Interspersed will be proposals for future research that may illuminate the clinical relevance of the relationships between sleeping, sleep loss and immune function in humans. Copyright 2001 by W.B. Saunders Company.

  16. 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.

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

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    Rommie E Amaro

    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.

  18. Neuroimaging of sleep and sleep disorders.

    Science.gov (United States)

    Nofzinger, Eric A

    2006-03-01

    Herein are presented the results of research in the area of sleep neuroimaging over the past year. Significant work has been performed to clarify the basic mechanisms of sleep in humans. New studies also extend prior observations regarding altered brain activation in response to sleep deprivation by adding information regarding vulnerability to sleep deprivation and regarding the influence of task difficulty on aberrant responses. Studies in sleep disorder medicine have yielded significant findings in insomnia, depression, and restless legs syndrome. Extensive advances have been made in the area of sleep apnea where physiologic challenges have been used to probe brain activity in the pathophysiology of sleep apnea syndrome.

  19. Mitochondrial outer membrane proteome of Trypanosoma brucei reveals novel factors required to maintain mitochondrial morphology.

    Science.gov (United States)

    Niemann, Moritz; Wiese, Sebastian; Mani, Jan; Chanfon, Astrid; Jackson, Christopher; Meisinger, Chris; Warscheid, Bettina; Schneider, André

    2013-02-01

    Trypanosoma brucei is a unicellular parasite that causes devastating diseases in humans and animals. It diverged from most other eukaryotes very early in evolution and, as a consequence, has an unusual mitochondrial biology. Moreover, mitochondrial functions and morphology are highly regulated throughout the life cycle of the parasite. The outer mitochondrial membrane defines the boundary of the organelle. Its properties are therefore key for understanding how the cytosol and mitochondria communicate and how the organelle is integrated into the metabolism of the whole cell. We have purified the mitochondrial outer membrane of T. brucei and characterized its proteome using label-free quantitative mass spectrometry for protein abundance profiling in combination with statistical analysis. Our results show that the trypanosomal outer membrane proteome consists of 82 proteins, two-thirds of which have never been associated with mitochondria before. 40 proteins share homology with proteins of known functions. The function of 42 proteins, 33 of which are specific to trypanosomatids, remains unknown. 11 proteins are essential for the disease-causing bloodstream form of T. brucei and therefore may be exploited as novel drug targets. A comparison with the outer membrane proteome of yeast defines a set of 17 common proteins that are likely present in the mitochondrial outer membrane of all eukaryotes. Known factors involved in the regulation of mitochondrial morphology are virtually absent in T. brucei. Interestingly, RNAi-mediated ablation of three outer membrane proteins of unknown function resulted in a collapse of the network-like mitochondrion of procyclic cells and for the first time identified factors that control mitochondrial shape in T. brucei.

  20. Sleep Apnea

    Science.gov (United States)

    ... of other risk factors linked to a higher risk of heart disease. The conditions that make up metabolic syndrome include high blood pressure, abnormal cholesterol, high blood sugar and an increased waist circumference. Complications with medications and surgery. Obstructive sleep apnea ...

  1. Diagnosing Sleep Disorders

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Sleep Disorders Diagnosing Sleep Disorders Past Issues / Summer 2015 Table of Contents Depending ... several possible tests when trying to diagnose a sleep disorder: Sleep history and sleep log If you believe ...

  2. Sleep Deprivation and Deficiency

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Are Sleep Deprivation and Deficiency? Sleep deprivation (DEP-rih-VA-shun) is a condition that ... the following: You don't get enough sleep (sleep deprivation) You sleep at the wrong time of day ( ...

  3. Advances in Sleep Studies

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Sleep Disorders Advances in Sleep Studies Past Issues / Summer 2015 ... is the director of the National Center on Sleep Disorders Research (NCSDR) in the NIH's National Heart, Lung, ...

  4. Sleep Disorders (PDQ)

    Science.gov (United States)

    ... to sleep and wake at the right times. Parasomnia : Acting in unusual ways while falling asleep, sleeping, ... will suggest a sleep disorder clinic for treatment. Children with Somnolence Syndrome Somnolence syndrome (SS) is a side ...

  5. Employees with Sleep Disorders

    Science.gov (United States)

    ... Cataplexy (a weakness or paralysis of the muscles), sleep paralysis, and hallucinations are common symptoms of narcolepsy (Neurology Channel, 2005). Hypersomnia: Hypersomnia’s symptoms include excessive ... by extended sleep episodes or by daytime sleep episodes that occur ...

  6. Isolated sleep paralysis

    Science.gov (United States)

    Sleep paralysis - isolated; Parasomnia - isolated sleep paralysis ... Episodes of isolated sleep paralysis last from a few seconds to 1 or 2 minutes. During these episodes the person is unable to move ...

  7. Sleep Apnea Information Page

    Science.gov (United States)

    ... Page You are here Home » Disorders » All Disorders Sleep Apnea Information Page Sleep Apnea Information Page Search Disorders Search NINDS SEARCH ... Institutes of Health (NIH) conduct research related to sleep apnea in laboratories at the NIH, and also ...

  8. 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 ...

  9. Sleep Issues and Sundowning

    Science.gov (United States)

    ... We will not sell or share your name. Sleep Issues and Sundowning Tweet Bookmark this page | Email | ... Sleep Changes Back to top Coping strategies for sleep issues and sundowning If the person is awake ...

  10. Sleep Eduction: Treatment & Therapy

    Science.gov (United States)

    ... Overview Testing Process & Results CPAP Overview Benefits Side Effects Variations Tips Healthy Sleep Habits Sleep Disorders by Category Insomnias Insomnia Child Insomnia Short Sleeper Hypersomnias Narcolepsy Insufficient ...

  11. Sleep Talking (Somniloquy)

    Science.gov (United States)

    ... Overview Testing Process & Results CPAP Overview Benefits Side Effects Variations Tips Healthy Sleep Habits Sleep Disorders by Category Insomnias Insomnia Child Insomnia Short Sleeper Hypersomnias Narcolepsy Insufficient ...

  12. Agrochemicals against malaria, sleeping sickness, leishmaniasis and Chagas disease.

    Directory of Open Access Journals (Sweden)

    Matthias Witschel

    Full Text Available In tropical regions, protozoan parasites can cause severe diseases with malaria, leishmaniasis, sleeping sickness, and Chagas disease standing in the forefront. Many of the drugs currently being used to treat these diseases have been developed more than 50 years ago and can cause severe adverse effects. Above all, resistance to existing drugs is widespread and has become a serious problem threatening the success of control measures. In order to identify new antiprotozoal agents, more than 600 commercial agrochemicals have been tested on the pathogens causing the above mentioned diseases. For all of the pathogens, compounds were identified with similar or even higher activities than the currently used drugs in applied in vitro assays. Furthermore, in vivo activity was observed for the fungicide/oomyceticide azoxystrobin, and the insecticide hydramethylnon in the Plasmodium berghei mouse model, and for the oomyceticide zoxamide in the Trypanosoma brucei rhodesiense STIB900 mouse model, respectively.

  13. 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

  14. Clinical and hematological study of Trypanosoma brucei and Trypanosoma congolense in cattle in Mosul City, Iraq

    Directory of Open Access Journals (Sweden)

    Al-Badrani, B. A

    2012-03-01

    Full Text Available An out-break of trypanosomosis was reported and subsequently investigated in Mosul city, Iraq. Twenty seven blood samples were received at the Clinical pathology Laboratory of Veterinary Teaching Hospital, University of Mosul, from fifteen cows (2-5 years old and twelve calves (10-12 months old of different farms located around Mosul city. Clinical signs of the infected animals revealed fever, progressive weight loss, anemia, and frequent recumbent position. Identification of trypanosome species were based on their motility using morphological differentiation on Giemsa or Leishman stained that showed trypomastigot which can be classified according to the biometrical data into T. brucei and T. congolense. A decreased was also observed in some blood parameters. To our knowledge, this is the first record of T. brucei and T. congolense infection in cattle. This study also suggested that trypanosomosis is associated with introduction of exotic breeds of cattle into Mosul, Iraq.

  15. 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.

  16. Identification of trypanosomes in wild animals from Southern Cameroon using the polymerase chain reaction (PCR

    Directory of Open Access Journals (Sweden)

    Herder S.

    2002-12-01

    Full Text Available One possible explanation of the maintenance of many historical foci of sleeping sickness in Central Africa could be the existence of a wild animal reservoir. In this study, PCR was used to detect the different trypanosome species present in wild animal captured by hunters in the southern forest belt of Cameroon (Bipindi. Trypanosomes were also detected by a parasitological method (Quantitative buffy coat : QBC. Parasite could not be isolated in culture medium (Kit for in vitro isolation : KIVI. Specific primers of T. brucei s.l., T. congolense forest type, T. congolense savannah type, T. vivax, T. simiae and T. b. gambiense group 1 were used to identify parasites in the blood of 164 animals belonging to 24 different species including ungulates, rodents, pangolins, carnivores, reptiles and primates. Of the 24 studied species, eight were carrying T. b. gambiense group 1. Those parasites pathogenic to man were found in monkeys (Cercocebus torquatus and Cercopithecus nictitans, in ungulates (Cephalophus dorsalis and C. monticola, in carnivores (Nandinia binotata and Genetta servalina and in rodents (Cricetomys gambianus and Atherurus africanus. 13 species (54 % were carrying T. brucei s.l. identified as non-gambiense group 1.

  17. Sleep problems in children.

    Science.gov (United States)

    Baweja, R; Calhoun, S; Baweja, R; Singareddy, R

    2013-10-01

    Sleep complaints and sleep disorders are common during childhood and adolescence. The impact of not getting enough sleep may affect children's' physical health as well emotional, cognitive and social development. Insomnia, sleep-disordered breathing, parasomnias and sleep disturbances associated with medical and psychiatric disorders are some of the commonly encountered sleep disorders in this age group. Changes in sleep architecture and the amount of sleep requirement associated with each stage of development should be considered during an evaluation of sleep disorders in children. Behavioral treatments should be used initially wherever possible especially considering that most pharmacologic agents used to treat pediatric sleep disorders are off-label. In this review we address the most common sleep problems in children/adolescents as they relate to prevalence, presentation and symptoms, evaluation and management.

  18. SLEEP DISORDERS, SLEEP APNEA. AND STROKE

    Institute of Scientific and Technical Information of China (English)

    ANTONIO CULEBRAS, M.D

    2000-01-01

    @@Sleep is the natural suspension of consciousness during which the powers of the body are restored Sleep recurs with remarkable periodicity in alliance with the geocosmic cycle and in compliance with the circadian rhythms of the body.

  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. 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

  1. An essential signal peptide peptidase identified in an RNAi screen of serine peptidases of Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Catherine X Moss

    Full Text Available The serine peptidases of Trypanosoma brucei have been viewed as potential drug targets. In particular, the S9 prolyl oligopeptidase subfamily is thought to be a good avenue for drug discovery. This is based on the finding that some S9 peptidases are secreted and active in the mammalian bloodstream, and that they are a class of enzyme against which drugs have successfully been developed. We collated a list of all serine peptidases in T. brucei, identifying 20 serine peptidase genes, of which nine are S9 peptidases. We screened all 20 serine peptidases by RNAi to determine which, if any, are essential for bloodstream form T. brucei survival. All S9 serine peptidases were dispensable for parasite survival in vitro, even when pairs of similar genes, coding for oligopeptidase B or prolyl oligopeptidase, were targeted simultaneously. We also found no effect on parasite survival in an animal host when the S9 peptidases oligopeptidase B, prolyl oligopeptidase or dipeptidyl peptidase 8 were targeted. The only serine peptidase to emerge from the RNAi screen as essential was a putative type-I signal peptide peptidase (SPP1. This gene was essential for parasite survival both in vitro and in vivo. The growth defect conferred by RNAi depletion of SPP1 was rescued by expression of a functional peptidase from an RNAi resistant SPP1 gene. However, expression of catalytically inactive SPP1 was unable to rescue cells from the SPP1 depleted phenotype, demonstrating that SPP1 serine peptidase activity is necessary for T. brucei survival.

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

    OpenAIRE

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

    2015-01-01

    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-silencin...

  3. 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

  4. 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.

  5. Experimental Trypanosoma brucei infection at immediate post partum period:effects on dam and the offspring

    Institute of Scientific and Technical Information of China (English)

    Izuchukwu S Ochiogu; Chukwuka N Uchendu; John I Ihedioha

    2010-01-01

    Objective:To investigate the effects of immediate post-partum infection with Trypanosoma brucei (T. brucei) on dam and offspring. Methods:Sixty female Albino rats (Rattus norvegicus) weighing between 130-170 g were used as animal model. The animals were divided as follows:25 infected between 1-5 days post partum; 10 infected unbred as positive controls; and 25 uninfected as negative controls. The following parameters were evaluated:packed cell volume (PCV), level of parasitaemia, survival time, litter size and litter weight at birth and on days 7, 14 and 21 post delivery, using conventional methods. Possible trans-mammary transmission of infection to litter through milk was also assessed. Results:The results showed a comparatively (P<0.05) higher mean PCV value for the uninfected negative control on the 8th day post infection compared with the infected groups which corresponded with the increasing level of parasitaemia in the two infected groups. Mean litter size and litter weights were higher (P< 0.05) in the uninfected controls on the 21st day. Survival time in the infected groups were similar. No evidence of trans-mammary transfer of infection was recorded. Conclusion:T. brucei infection during immediate post partum period is detrimental to the dam and impairs growth of the offspring.

  6. Advancing Trypanosoma brucei genome annotation through ribosome profiling and spliced leader mapping.

    Science.gov (United States)

    Parsons, Marilyn; Ramasamy, Gowthaman; Vasconcelos, Elton J R; Jensen, Bryan C; Myler, Peter J

    2015-08-01

    Since the initial publication of the trypanosomatid genomes, curation has been ongoing. Here we make use of existing Trypanosoma brucei ribosome profiling data to provide evidence of ribosome occupancy (and likely translation) of mRNAs from 225 currently unannotated coding sequences (CDSs). A small number of these putative genes correspond to extra copies of previously annotated genes, but 85% are novel. The median size of these novels CDSs is small (81 aa), indicating that past annotation work has excelled at detecting large CDSs. Of the unique CDSs confirmed here, over half have candidate orthologues in other trypanosomatid genomes, most of which were not yet annotated as protein-coding genes. Nonetheless, approximately one-third of the new CDSs were found only in T. brucei subspecies. Using ribosome footprints, RNA-Seq and spliced leader mapping data, we updated previous work to definitively revise the start sites for 414 CDSs as compared to the current gene models. The data pointed to several regions of the genome that had sequence errors that altered coding region boundaries. Finally, we consolidated this data with our previous work to propose elimination of 683 putative genes as protein-coding and arrive at a view of the translatome of slender bloodstream and procyclic culture form T. brucei.

  7. Discovery of Inhibitors of Trypanosoma brucei by Phenotypic Screening of a Focused Protein Kinase Library.

    Science.gov (United States)

    Woodland, Andrew; Thompson, Stephen; Cleghorn, Laura A T; Norcross, Neil; De Rycker, Manu; Grimaldi, Raffaella; Hallyburton, Irene; Rao, Bhavya; Norval, Suzanne; Stojanovski, Laste; Brun, Reto; Kaiser, Marcel; Frearson, Julie A; Gray, David W; Wyatt, Paul G; Read, Kevin D; Gilbert, Ian H

    2015-11-01

    A screen of a focused kinase inhibitor library against Trypanosoma brucei rhodesiense led to the identification of seven series, totaling 121 compounds, which showed >50 % inhibition at 5 μm. Screening of these hits in a T. b. brucei proliferation assay highlighted three compounds with a 1H-imidazo[4,5-b]pyrazin-2(3H)-one scaffold that showed sub-micromolar activity and excellent selectivity against the MRC5 cell line. Subsequent rounds of optimisation led to the identification of compounds that exhibited good in vitro drug metabolism and pharmacokinetics (DMPK) properties, although in general this series suffered from poor solubility. A scaffold-hopping exercise led to the identification of a 1H-pyrazolo[3,4-b]pyridine scaffold, which retained potency. A number of examples were assessed in a T. b. brucei growth assay, which could differentiate static and cidal action. Compounds from the 1H-imidazo[4,5-b]pyrazin-2(3H)-one series were found to be either static or growth-slowing and not cidal. Compounds with the 1H-pyrazolo[3,4-b]pyridine scaffold were found to be cidal and showed an unusual biphasic nature in this assay, suggesting they act by at least two mechanisms.

  8. 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.

  9. 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…

  10. Framing tropical disease in London: Patrick Manson, Filaria perstans, and the Uganda sleeping sickness epidemic, 1891-1902.

    Science.gov (United States)

    Haynes, D M

    2000-12-01

    Much of the historical literature on tropical medicine represents the periphery as the chief site for the production of western knowledge about disease in the British empire. This study on the Filaria perstans-sleeping sickness hypothesis revises this perspective by showing how the imperial metropole functioned as a culture space for the construction of knowledge about the empire. Beginning in 1891, Patrick Manson used the publicity resources of London to generate a rhetorical imperative for the confirmation of his hypothesis without ever leaving Britain. Later, while he was medical adviser to the imperial state, the 1900 sleeping sickness epidemic in Uganda presented Manson with a unique opportunity to determine the validity of his hypothesis. By exaggerating the possible spread of the epidemic privately among Foreign Office personnel and publicly in the medical press, he succeeded in mobilizing the first Royal Society sleeping sickness research expedition to Africa in 1902. While this expedition ultimately disproved Manson's hypothesis, this outcome ironically created the very conditions for the identification of the actual causal agent (Trypanosoma gambiense) and its vector (tsetse fly) by Aldo Castellani and David Bruce respectively.

  11. Sleeping with an Android

    Science.gov (United States)

    2017-01-01

    Sleep quality and duration are strong indicators of an individual’s health and quality of lifebut they are difficult to track in everyday life. Mobile apps such as Sleep as Android leverage smartphone sensors to track sleep patterns and make recommendations to improve sleeping habits. PMID:28293622

  12. 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…

  13. Sleep and Stroke.

    Science.gov (United States)

    Mims, Kimberly Nicole; Kirsch, Douglas

    2016-03-01

    Evidence increasingly suggests sleep disorders are associated with higher risk of cardiovascular events, including stroke. Strong data correlate untreated sleep apnea with poorer stroke outcomes and more recent evidence implicates sleep disruption as a possible etiology for increased cerebrovascular events. Also, sleep duration may affect incidence of cardiovascular events. In addition, sleep-disordered breathing, insomnia, restless legs syndrome, and parasomnias can occur as a result of cerebrovascular events. Treatment of sleep disorders improve sleep-related symptoms and may also improve stroke recovery and risk of future events.

  14. Movement disorders and sleep.

    Science.gov (United States)

    Driver-Dunckley, Erika D; Adler, Charles H

    2012-11-01

    This article summarizes what is currently known about sleep disturbances in several movement disorders including Parkinson disease, essential tremor, parkinsonism, dystonia, Huntington disease, myoclonus, and ataxias. There is an association between movement disorders and sleep. In some cases the prevalence of sleep disorders is much higher in patients with movement disorder, such as rapid eye movement sleep behavior disorder in Parkinson disease. In other cases, sleep difficulties worsen the involuntary movements. In many cases the medications used to treat patients with movement disorder disturb sleep or cause daytime sleepiness. The importance of discussing sleep issues in patients with movement disorders cannot be underestimated.

  15. 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.

  16. Sleep, sleep disturbance, and fertility in women.

    Science.gov (United States)

    Kloss, Jacqueline D; Perlis, Michael L; Zamzow, Jessica A; Culnan, Elizabeth J; Gracia, Clarisa R

    2015-08-01

    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.

  17. Childhood epilepsy and sleep

    OpenAIRE

    Al-Biltagi, Mohammed A

    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...

  18. Identification of potent inhibitors of the Trypanosoma brucei methionyl-tRNA synthetase via high-throughput orthogonal screening.

    Science.gov (United States)

    Pedró-Rosa, Laura; Buckner, Frederick S; Ranade, Ranae M; Eberhart, Christina; Madoux, Franck; Gillespie, J Robert; Koh, Cho Yeow; Brown, Steven; Lohse, Jacqueline; Verlinde, Christophe L M; Fan, Erkang; Bannister, Thomas; Scampavia, Louis; Hol, Wim G J; Spicer, Timothy; Hodder, Peter

    2015-01-01

    Improved therapies for the treatment of Trypanosoma brucei, the etiological agent of the neglected tropical disease human African trypanosomiasis, are urgently needed. We targeted T. brucei methionyl-tRNA synthetase (MetRS), an aminoacyl-tRNA synthase (aaRS), which is considered an important drug target due to its role in protein synthesis, cell survival, and its significant differences in structure from its mammalian ortholog. Previous work using RNA interference of MetRS demonstrated growth inhibition of T. brucei, further validating it as an attractive target. We report the development and implementation of two orthogonal high-throughput screening assays to identify inhibitors of T. brucei MetRS. First, a chemiluminescence assay was implemented in a 1536-well plate format and used to monitor adenosine triphosphate depletion during the aminoacylation reaction. Hit confirmation then used a counterscreen in which adenosine monophosphate production was assessed using fluorescence polarization technology. In addition, a miniaturized cell viability assay was used to triage cytotoxic compounds. Finally, lower throughput assays involving whole parasite growth inhibition of both human and parasite MetRS were used to analyze compound selectivity and efficacy. The outcome of this high-throughput screening campaign has led to the discovery of 19 potent and selective T. brucei MetRS inhibitors.

  19. The Centriole Cartwheel Protein SAS-6 in Trypanosoma brucei Is Required for Probasal Body Biogenesis and Flagellum Assembly.

    Science.gov (United States)

    Hu, Huiqing; Liu, Yi; Zhou, Qing; Siegel, Sara; Li, Ziyin

    2015-09-01

    The centriole in eukaryotes functions as the cell's microtubule-organizing center (MTOC) to nucleate spindle assembly, and its biogenesis requires an evolutionarily conserved protein, SAS-6, which assembles the centriole cartwheel. Trypanosoma brucei, an early branching protozoan, possesses the basal body as its MTOC to nucleate flagellum biogenesis. However, little is known about the components of the basal body and their roles in basal body biogenesis and flagellum assembly. Here, we report that the T. brucei SAS-6 homolog, TbSAS-6, is localized to the mature basal body and the probasal body throughout the cell cycle. RNA interference (RNAi) of TbSAS-6 inhibited probasal body biogenesis, compromised flagellum assembly, and caused cytokinesis arrest. Surprisingly, overexpression of TbSAS-6 in T. brucei also impaired probasal body duplication and flagellum assembly, contrary to SAS-6 overexpression in humans, which produces supernumerary centrioles. Furthermore, we showed that depletion of T. brucei Polo-like kinase, TbPLK, or inhibition of TbPLK activity did not abolish TbSAS-6 localization to the basal body, in contrast to the essential role of Polo-like kinase in recruiting SAS-6 to centrioles in animals. Altogether, these results identified the essential role of TbSAS-6 in probasal body biogenesis and flagellum assembly and suggest the presence of a TbPLK-independent pathway governing basal body duplication in T. brucei.

  20. Functional neuroimaging of sleep.

    Science.gov (United States)

    Nofzinger, Eric A

    2005-03-01

    Sleep and sleep disorders have traditionally been viewed from a polysomnographic perspective. Although these methods provide information on the timing of various stages of sleep and wakefulness, they do not provide information regarding function in brain structures that have been implicated in the generation of sleep and that may be abnormal in different sleep disorders. Functional neuroimaging methods provide information regarding changes in brain function across the sleep-wake cycle that provides information for models of sleep dysregulation in a variety of sleep disorders. Early studies show reliable increases in function in limbic and anterior paralimbic cortex in rapid eye movement (REM) sleep and decreases in function in higher-order cortical regions in known thalamocortical networks during non-REM sleep. Although most of the early work in this area has been devoted to the study of normal sleep mechanisms, a collection of studies in diverse sleep disorders such as sleep deprivation, depression, insomnia, dyssomnias, narcolepsy, and sleep apnea suggest that functional neuroimaging methods have the potential to clarify the pathophysiology of sleep disorders and to guide treatment strategies.

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

    OpenAIRE

    Molfese, Victoria J.; Rudasill, Kathleen M.; Prokasky, Amanda; Champagne, Carly; Holmes, Molly; Molfese, Dennis; Bates, Jack

    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 characteri...

  2. 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.

  3. Are You Getting Enough Sleep?

    Science.gov (United States)

    ... Past Emails CDC Features Are you getting enough sleep? Recommend on Facebook Tweet Share Compartir Sleep is ... sleep guidelines for different age groups. How much sleep do you need? Newborns 16-18 hours Preschool- ...

  4. Shift Work: Improving Daytime Sleep

    Science.gov (United States)

    ... sleeping during the day. Do you have any sleep tips for shift workers? Answers from Timothy Morgenthaler, ... to be awake during the day and to sleep at night. Good daytime sleep is possible, though, ...

  5. The Phenomenon of Sleep Paralysis

    Science.gov (United States)

    ... of sleep where vivid dreams occur (known as REM sleep), your arms and legs are temporarily paralyzed so ... alien abductions." Since breathing can be irregular during REM sleep, those experiencing sleep paralysis may feel like they' ...

  6. Sleep from an Islamic perspective

    OpenAIRE

    BaHammam, Ahmed S.

    2011-01-01

    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 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 ...

  7. 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.

  8. 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.

  9. [Actigraphy in sleep medicine and sleep research].

    Science.gov (United States)

    Tamura, Yoshiyuki; Matsuda, Mika; Chiba, Shigeru

    2009-08-01

    Actigraphy is a method that utilizes a miniaturized computerized wristwatch-like device to monitor and collect data generated by body movements over extended periods of time. It allows estimation of sleep and wakefulness based on motor activity. It provides a noninvasive, objective, and longitudinal method for the diagnostic and post-treatment evaluation of patients with sleep disorders in the ambulatory setting. It has been used for researchers to study sleep disturbances in a variety of populations, most frequently for the evaluation of insomnia, paradoxical insomnia, and circadian rhythm sleep disorders. In addition, it is particularly useful in populations where polysomnography would be difficult to record, such as in patients with dementia and delirium. Actigraphy should be extensively carried out in sleep medicine as well as sleep research.

  10. Sleep and sleep disorders in Don Quixote.

    Science.gov (United States)

    Iranzo, Alex; Santamaria, Joan; de Riquer, Martín

    2004-01-01

    In Don Quijote de la Mancha, Miguel de Cervantes presents Don Quixote as an amazing character of the 17th century who suffers from delusions and illusions, believing himself to be a medieval knight errant. Besides this neuropsychiatric condition, Cervantes included masterful descriptions of several sleep disorders such as insomnia, sleep deprivation, disruptive loud snoring and rapid eye movement sleep behaviour disorder. In addition, he described the occurrence of physiological, vivid dreams and habitual, post-prandial sleepiness--the siesta. Cervantes' concept of sleep as a passive state where all cerebral activities are almost absent is in conflict with his description of abnormal behaviours during sleep and vivid, fantastic dreams. His concept of sleep was shared by his contemporary, Shakespeare, and could have been influenced by the reading of the classical Spanish book of psychiatry Examen de Ingenios (1575).

  11. Central Nervous System Parasitosis and Neuroinflammation Ameliorated by Systemic IL-10 Administration in Trypanosoma brucei-Infected Mice.

    Science.gov (United States)

    Rodgers, Jean; Bradley, Barbara; Kennedy, Peter G E; Sternberg, Jeremy M

    2015-01-01

    Invasion of the central nervous system (CNS) by African trypanosomes represents a critical step in the development of human African trypanosomiasis. In both clinical cases and experimental mouse infections it has been demonstrated that predisposition to CNS invasion is associated with a type 1 systemic inflammatory response. Using the Trypanosoma brucei brucei GVR35 experimental infection model, we demonstrate that systemic delivery of the counter-inflammatory cytokine IL-10 lowers plasma IFN-γ and TNF-α concentrations, CNS parasitosis and ameliorates neuro-inflammatory pathology and clinical symptoms of disease. The results provide evidence that CNS invasion may be susceptible to immunological attenuation.

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

    Directory of Open Access Journals (Sweden)

    Nikolay G Kolev

    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.

  13. Sleep disturbances in Parkinsonism.

    Science.gov (United States)

    Askenasy, J J M

    2003-02-01

    The present article is meant to suggest an approach to the guidelines for the therapy of sleep disturbances in Parkinson's Disease (PD) patients.The factors affecting the quality of life in PD patients are depression, sleep disturbances and dependence. A large review of the literature on sleep disturbances in PD patients, provided the basis for the following classification of the sleep-arousal disturbances in PD patients. We suggest a model based on 3 steps in the treatment of sleep disturbances in PD patients. This model allowing the patient, the spouse or the caregiver a quiet sleep at night, may postpone the retirement and the institutionalization of the PD patient. I. Correct diagnosis of sleep disorders based on detailed anamnesis of the patient and of the spouse or of the caregiver. One week recording on a symptom diary (log) by the patient or the caregiver. Correct diagnosis of sleep disorders co morbidities. Selection of the most appropriate sleep test among: polysomnography (PSG), multiple sleep latency test (MSLT), multiple wake latency test (MWLT), Epworth Sleepiness Scale, actigraphy or video-PSG. II. The nonspecific therapeutic approach consists in: a) Checking the sleep effect on motor performance, is it beneficial, worse or neutral. b) Psycho-physical assistance. c) Dopaminergic adjustment is necessary owing to the progression of the nigrostriatal degeneration and the increased sensitivity of the terminals, which alter the normal modulator mechanisms of the motor centers in PD patients. Among the many neurotransmitters of the nigro-striatal pathway one can distinguish two with a major influence on REM and NonREM sleep. REM sleep corresponds to an increased cholinergic receptor activity and a decreased dopaminergic activity. This is the reason why REM sleep deprivation by suppressing cholinergic receptor activity ameliorates PD motor symptoms. L-Dopa and its agonists by suppressing cholinergic receptors suppress REM sleep. The permanent adjustment

  14. Trypanocidal activity of organotin chlorides on Trypanosoma brucei-infected mice

    Directory of Open Access Journals (Sweden)

    Shuaibu M.N.

    2000-03-01

    Full Text Available The organotin compounds dibulyltin (DBTC and diphenyltin dichlorides (DPTC were tested for trypanocidal activity on a Trypanosoma brucei-infected mice model. At a dose of 10 mg DBTC and 15 mg DPTC/kg/day for five consecutive days, they cleared the parasites from the peripheral blood of the infected mice. Subinoculation of some healthy mice with the homogenates of liver, spleen, kidney, cerebrospinal fluid and blood from the mice considered cured, showed a few cases of relapse. The LD50 of DBTC and DPTC are 90 mg/kg and 75 mg/kg respectively.

  15. A haptoglobin-hemoglobin receptor conveys innate immunity to Trypanosoma brucei in humans

    DEFF Research Database (Denmark)

    Vanhollebeke, Benoit; De Muylder, Géraldine; Nielsen, Marianne J;

    2008-01-01

    The protozoan parasite Trypanosoma brucei is lysed by apolipoprotein L-I, a component of human high-density lipoprotein (HDL) particles that are also characterized by the presence of haptoglobin-related protein. We report that this process is mediated by a parasite glycoprotein receptor, which...... receptor also recognized the complex between hemoglobin and haptoglobin-related protein, which explains its ability to capture trypanolytic HDLs. Thus, in humans the presence of haptoglobin-related protein has diverted the function of the trypanosome haptoglobin-hemoglobin receptor to elicit innate host...

  16. 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

    2017-02-20

    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.

  17. Structures of aspartate aminotransferases from Trypanosoma brucei, Leishmania major and Giardia lamblia.

    Science.gov (United States)

    Abendroth, Jan; Choi, Ryan; Wall, Abigail; Clifton, Matthew C; Lukacs, Christine M; Staker, Bart L; Van Voorhis, Wesley; Myler, Peter; Lorimer, Don D; Edwards, Thomas E

    2015-05-01

    The structures of three aspartate aminotransferases (AATs) from eukaryotic pathogens were solved within the Seattle Structural Genomics Center for Infectious Disease (SSGCID). Both the open and closed conformations of AAT were observed. Pyridoxal phosphate was bound to the active site via a Schiff base to a conserved lysine. An active-site mutant showed that Trypanosoma brucei AAT still binds pyridoxal phosphate even in the absence of the tethering lysine. The structures highlight the challenges for the structure-based design of inhibitors targeting the active site, while showing options for inhibitor design targeting the N-terminal arm.

  18. Sleep and Newborns

    Science.gov (United States)

    ... AAP introduced this recommendation in 1992. Use a firm sleep surface. Cover the mattress with a sheet ... Sleep and Your 1- to 2-Year-Old Communication and Your Newborn Medical Care and Your Newborn ...

  19. 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.

  20. Central sleep apnea

    Science.gov (United States)

    ... diagnose an underlying medical condition. A sleep study (polysomnography) can confirm sleep apnea. Other tests that may ... MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow us Disclaimers Copyright Privacy ...

  1. Polysomnography (Sleep Study)

    Science.gov (United States)

    ... make symptoms of some sleep disorders worse. During polysomnography You arrive at the sleep center in the ... t required to obtain accurate polysomnography results. After polysomnography In the morning, the sensors are removed, and ...

  2. Sleep in postmenopausal women.

    Science.gov (United States)

    Vigeta, Sônia Maria Garcia; Hachul, Helena; Tufik, Sergio; de Oliveira, Eleonora Menicucci

    2012-04-01

    The aim of this study was to identify factors that most influence the perception of sleep quality in postmenopausal women. We used the methodological strategy of the Collective Subject Discourse (CSD), which is based on a theoretical framework of social representations theory. We obtained the data by interviewing 22 postmenopausal Brazilian women who were experiencing insomnia. The women gave accounts of their difficulties with sleep; a variety of dimensions were identified within the data. The onset of sleep disorders might have occurred during childhood or in situations considered to be stressful, and were not necessarily associated with menopause. We found that hormonal alterations occurring during menopause, psychosocial factors, and sleep-breathing disorders triggered occasional sleep disturbances during this time of life. Participants were aware of the consequences of sleep deprivation. In addition, inadequate sleep hygiene habits figured prominently as determinants in the persistence of sleep disturbances.

  3. Metformin and sleep disorders

    OpenAIRE

    2012-01-01

    Metformin is a widely used anti-diabetic drug. Deterioration of sleep is an important unwanted side effect of metformin. Here, the authors review and present the details on metformin and sleep problem.

  4. Teenagers and sleep

    Science.gov (United States)

    ... and with their health , including: Depression and low self esteem Sleepiness and trouble concentrating Decline in school performance ... associated with improved sleep and daytime functioning in adolescents. Sleep . 2011;34(6):797-800. PMID: 21629368 ...

  5. Sleep and Newborns

    Science.gov (United States)

    ... 12-Month-Old Bed-Sharing All About Sleep Sleep and Your 1- to 2-Year-Old Communication and Your Newborn Medical Care and Your Newborn Your Newborn's Growth Choosing Safe Baby Products: Cribs Flat Head Syndrome ( ...

  6. Sleep hygiene and sleep quality in Italian and American adolescents.

    Science.gov (United States)

    LeBourgeois, Monique K; Giannotti, Flavia; Cortesi, Flavia; Wolfson, Amy; Harsh, John

    2004-06-01

    This study investigated cross-cultural differences in adolescent sleep hygiene and sleep quality. Participants were 1348 students (655 males; 693 females) aged 12-17 years from public school systems in Rome, Italy (n = 776) and Southern Mississippi (n = 572). Participants completed the Adolescent Sleep-Wake Scale and the Adolescent Sleep Hygiene Scale. Reported sleep hygiene and sleep quality were significantly better for Italian than American adolescents. A moderate linear relationship was observed between sleep hygiene and sleep quality in both samples (Italians: R =.40; Americans: R =.46). Separate hierarchical multiple regression analyses showed that sleep hygiene accounted for significant variance in sleep quality, even after controlling for demographic and health variables (Italians: R(2) =.38; Americans: R(2) =.44). The results of this study suggest that there are cultural differences in sleep quality and sleep hygiene practices, and that sleep hygiene practices are importantly related to adolescent sleep quality.

  7. Sleep hygiene and actigraphically evaluated sleep characteristics in children with ADHD and chronic sleep onset insomnia.

    Science.gov (United States)

    van der Heijden, Kristiaan B; Smits, Marcel G; Gunning, W Boudewijn

    2006-03-01

    In the present study we investigated sleep hygiene and actigraphically evaluated sleep in 74 medication-naïve children, aged 6-12 years, with rigorously diagnosed attention-deficit/hyperactivity disorder (ADHD) and chronic sleep onset insomnia (ADHD-SOI) and 23 ADHD controls without insomnia (ADHD-noSOI). Between-group differences were analysed for lights out (sleep log), actigraphically evaluated sleep onset, sleep latency, total sleep duration, actual sleep time and sleep hygiene as measured with the Children's Sleep Hygiene Scale. We found a significant difference (P sleep hygiene score between the ADHD-SOI (56.4 +/- 10.5) and ADHD-noSOI groups (53.0 +/- 10.6). We conclude that there were differences in sleep onset and sleep latency in ADHD children with chronic SOI and those without insomnia; however, sleep hygiene practices were similar and did not relate to sleep characteristics.

  8. 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.

  9. Treatments for Sleep Changes

    Science.gov (United States)

    ... use the bed only for sleep Discourage watching television during periods of wakefulness Medications for sleep changes In some cases, non-drug approaches fail to work or the sleep changes are accompanied by disruptive nighttime behaviors. For those individuals who do require medication, experts ...

  10. 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.

  11. Snoring and Sleep Apnea

    Science.gov (United States)

    ... relations staff at newsroom@entnet.org . Insight into sleeping disorders and sleep apnea Forty-five percent of normal adults snore ... Witnessed episodes of breath pauses or apnea during sleep • Daytime sleepiness or fatigue • High ... disease • History of a stroke What treatments are available? ...

  12. Sleep and Your Preschooler

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Sleep and Your Preschooler KidsHealth > For Parents > Sleep and Your Preschooler Print A A A What's ... Preschoolers need about 11 to 12 hours of sleep each day, which can include a nap. There's ...

  13. Neuroimaging and sleep medicine.

    Science.gov (United States)

    Nofzinger, Eric A

    2005-06-01

    In sleep medicine, patients with sleep disorders are evaluated and treated. The primary assessment tool of the field has traditionally been polysomnography. While polysomnography has been helpful in the evaluation of some sleep disorders, such as sleep apnea syndrome and periodic limb movement disorder, it has been less helpful in others, such as the insomnias, or sleep disorders secondary to mental disorders. These disorders are presumed to stem from some alteration in brain function that disrupts sleep. The development of functional neuroimaging methods provides a means to understand brain function in patients with sleep disorders in a manner not accessible to polysomnography. This paper summarizes functional neuroimaging findings during healthy sleep, then, reviews available studies in sleep disorders patients, and studies addressing the pharmacology of sleep and sleep disorders. Areas in which functional neuroimaging methods may be helpful in sleep medicine, and in which future development is advised, include: (1) clarification of pathophysiology; (2) aid in differential diagnosis; (3) assessment of treatment response; (4) guiding new drug development; and (5) monitoring treatment response.

  14. 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.

  15. What Is Sleep Apnea?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Is Sleep Apnea? Español Sleep apnea (AP-ne-ah) is ... many people. Rate This Content: NEXT >> Featured Video Sleep Apnea Research: The HeartBeat Study 06/07/2012 ...

  16. Human African trypanosomiasis in endemic populations and travellers.

    Science.gov (United States)

    Blum, J A; Neumayr, A L; Hatz, C F

    2012-06-01

    Human African trypanosomiasis (HAT) or sleeping sickness is caused by the protozoan parasites Trypanosoma brucei (T.b.) gambiense (West African form) and T.b. rhodesiense (East African form) that are transmitted by the bite of the tsetse fly, Glossina spp.. Whereas most patients in endemic populations are infected with T.b. gambiense, most tourists are infected with T.b. rhodesiense. In endemic populations, T.b. gambiense HAT is characterized by chronic and intermittent fever, headache, pruritus, and lymphadenopathy in the first stage and by sleep disturbances and neuro-psychiatric disorders in the second stage. Recent descriptions of the clinical presentation of T.b. rhodesiense in endemic populations show a high variability in different foci. The symptomatology of travellers is markedly different from the usual textbook descriptions of African HAT patients. The onset of both infections is almost invariably an acute and febrile disease. Diagnosis and treatment are difficult and rely mostly on old methods and drugs. However, new molecular diagnostic technologies are under development. A promising new drug combination is currently evaluated in a phase 3 b study and further new drugs are under evaluation.

  17. Sleep and sleep disorders in menopausal women.

    Science.gov (United States)

    Guidozzi, F

    2013-04-01

    Sleep disorders in the menopause are common. Although these disorders may be due to the menopause itself and/or the associated vasomotor symptoms, the etiology is multifactorial and includes a number of other associated conditions. They may simply arise as part of the aging process and not be specifically related to the decrease in estrogen levels or, alternatively, because of breathing or limb movement syndromes, depression, anxiety, co-morbid medical diseases, medication, pain and/or psychosocial factors. The most commonly encountered sleep disorders in menopausal women include insomnia, nocturnal breathing disturbances and the associated sleep disorders that accompany the restless leg syndrome, periodic leg movement syndrome, depression and anxiety. This review article addresses sleep and the sleep disorders associated with menopause and briefly the role that hormone therapy may play in alleviating these disorders.

  18. Menopause related sleep disorders.

    Science.gov (United States)

    Eichling, Philip S; Sahni, Jyotsna

    2005-07-15

    Sleep difficulty is one of the hallmarks of menopause. Following recent studies showing no cardiac benefit and increased breast cancer, the question of indications for hormonal therapy has become even more pertinent. Three sets of sleep disorders are associated with menopause: insomnia/depression, sleep disordered breathing and fibromyalgia. The primary predictor of disturbed sleep architecture is the presence of vasomotor symptoms. This subset of women has lower sleep efficiency and more sleep complaints. The same group is at higher risk of insomnia and depression. The "domino theory" of sleep disruption leading to insomnia followed by depression has the most scientific support. Estrogen itself may also have an antidepressant as well as a direct sleep effect. Treatment of insomnia in responsive individuals may be a major remaining indication for hormone therapy. Sleep disordered breathing (SDB) increases markedly at menopause for reasons that include both weight gain and unclear hormonal mechanisms. Due to the general under-recognition of SDB, health care providers should not assume sleep complaints are due to vasomotor related insomnia/depression without considering SDB. Fibromyalgia has gender, age and probably hormonal associations. Sleep complaints are almost universal in FM. There are associated polysomnogram (PSG) findings. FM patients have increased central nervous system levels of the nociceptive neuropeptide substance P (SP) and lower serotonin levels resulting in a lower pain threshold to normal stimuli. High SP and low serotonin have significant potential to affect sleep and mood. Treatment of sleep itself seems to improve, if not resolve FM. Menopausal sleep disruption can exacerbate other pre-existing sleep disorders including RLS and circadian disorders.

  19. 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.

  20. Analysis of the Trypanosoma brucei cell cycle by quantitative DAPI imaging.

    Science.gov (United States)

    Siegel, T Nicolai; Hekstra, Doeke R; Cross, George A M

    2008-08-01

    Trypanosoma brucei has two DNA compartments: the nucleus and the kinetoplast. DNA replication of these two compartments only partially coincides. Woodward and Gull [Woodward R, Gull K. Timing of nuclear and kinetoplast DNA replication and early morphological events in the cell cycle of Trypanosoma brucei. J Cell Sci 1990;95:49-57] comprehensively studied the relative timing of the replication and segregation of nuclear DNA (nDNA) and kinetoplast DNA (kDNA). Others have since assumed the consistency of morphological indicators of cell-cycle stage among strains and conditions. We report the use of quantitative DAPI imaging to determine the cell-cycle stage of individual procyclic cells. Using this approach, we found that kinetoplast elongation occurs mainly during nuclear S phase and not during G2, as previously assumed. We confirmed this finding by sorting cells by DNA content, followed by fluorescence microscopy. In addition, simultaneous quantitative imaging at two wavelengths can be used to determine the abundance of cell-cycle-regulated proteins during the cell cycle. We demonstrate this technique by co-staining for the non-acetylated state of lysine 4 of histone H4 (H4K4), which is enriched during nuclear S phase.

  1. 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.

  2. Trypanosoma Brucei Aquaglyceroporins Facilitate the Uptake of Arsenite and Antimonite in a pH Dependent Way

    Directory of Open Access Journals (Sweden)

    Néstor L. Uzcátegui

    2013-09-01

    Full Text Available Background: Trypanosoma brucei is a primitive parasitic protozoan that thrives in diverse environments such as the midgut of the tsetse fly and the blood of a mammalian host. For an adequate adaptation to these environments, the parasite´s aquaglyceroporins play an important role. Methods and Results: In order to test their ability to transport trivalent arsenic and antimony, we expressed the three known Trypanosoma brucei aquaglyceroporins (TbAQPs in the heterologous systems of yeast null aquaporin mutant and Xenopus laevis oocytes. For both expression systems, we found a pH dependent intracellular accumulation of As(III or Sb(III mediated by all of the three TbAQPs, with the exception of TbAQP1-As(III uptake. Additionally, we observed that Trypanosoma brucei aquaglyceroporins allow the passage of As(III in both directions. Conclusion: Taken together, these results demonstrated that T. brucei aquaglyceroporins can serve as entry routes for As(III and Sb(III into the parasitic cell, and that this uptake is pH sensitive. Therefore, aquaporins of protozoan parasites may be considered useful as a vehicle for drug delivery.

  3. 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...

  4. Screening North American plant extracts in vitro against Trypanosoma brucei, the causative agent for Human African Trypanosomiasis

    Science.gov (United States)

    Natural products extracts from 522 plants collected from different parts of the North America were screened in vitro against trypamastigote forms of Trypanosoma brucei. The active extracts(150)with >90% inhibition at 20ug/mL concentrations from the plants namely, Alnus rubra, Hoita macrostachya, S...

  5. [Sleep and sexuality].

    Science.gov (United States)

    Abraham, G; Vlatkovic, D

    2006-03-22

    Our knowledge about the multiple aspects of sleep functions are still insufficient. Concerning the relationship between sleep and sexuality there are four points of view to take into account. Two observations: a spontaneous sexual excitement during REM sleep and that some anxious dreams can produce also sexual arousal. Two hypotheses: the erotic pleasure could be easier to perceive in a sleeping or dreaming state than in a waking state and some sleeping troubles could have an important influence on the sexual life of a couple.

  6. The neurology of sleep.

    Science.gov (United States)

    Swick, Todd J

    2005-11-01

    Neurology, by virtue of its study of the brain, is the primary medical science for the elucidation of the anatomy, physiology, pathology and, ultimately, the function of sleep. There has been nothing short of a revolution in the science of sleep over the past 50 years. From the discovery of REM sleep to the identification of Hypocretin/Orexin the basic science and clinical field of sleep medicine has blossomed. This article will explore the anatomy, physiology, biochemistry and, to a limited extent, pathophysiology of the sleep/wake centers of the brain. The field of chronobiology will also be touched upon.

  7. Autism and sleep disorders

    Directory of Open Access Journals (Sweden)

    Preeti A Devnani

    2015-01-01

    Full Text Available “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 sleep which included decreased quantity, increased undifferentiated sleep, immature organization of eye movements into discrete bursts, decreased time in bed, total sleep time, REM sleep latency, and increased proportion of stage 1 sleep. Implementation of nonpharmacotherapeutic measures such as bedtime routines and sleep-wise approach is the mainstay of behavioral management. Treatment strategies along with limited regulated pharmacotherapy can help improve the quality of life in ASD children and have a beneficial impact on the family. PubMed search was performed for English language articles from January 1995 to January 2015. Following key words: Autism spectrum disorder, sleep disorders and autism, REM sleep and autism, cognitive behavioral therapy, sleep-wise approach, melatonin and ASD were used. Only articles reporting primary data relevant to the above questions were included.

  8. 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

  9. 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…

  10. 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…

  11. 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...

  12. 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.

  13. 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.

  14. Cardiovascular physiology and sleep.

    Science.gov (United States)

    Murali, Narayana S; Svatikova, Anna; Somers, Virend K

    2003-05-01

    Sleep is a natural periodic suspension of consciousness during which processes of rest and restoration occur. The cognitive, reparative and regenerative accompaniments of sleep appear to be essential for maintenance of health and homeostasis. This brief overview will examine the cardiovascular responses to normal and disordered sleep, and their physiologic and pathologic implications. In the past, sleep was believed to be a passive state. The tableau of sleep as it unfolds is anything but a passive process. The brain's activity is as complex as wakefulness, never "resting" during sleep. Following the demise of the 'passive theory of sleep' (the reticular activating system is fatigued during the waking day and hence becomes inactive), there arose the 'active theory of sleep' (sleep is due to an active general inhibition of the brain) (1). Hess demonstrated the active nature of sleep in cats, inducing "physiological sleep" with electrical stimulation of the diencephalon (2). Classical experiments of transection of the cat brainstem (3) at midpontine level inhibited sleep completely, implying that centers below this level were involved in the induction of sleep (1, 4). For the first time, measurement of sleep depth without awakening the sleeper using the electroencephalogram (EEG) was demonstrated in animals by Caton and in humans, by Berger (1). This was soon followed by discovery of the rapid eye movement sleep periods (REM) by Aserinski and Kleitman (5), demonstration of periodical sleep cycles and their association with REM sleep (6, 7). Multiple studies and steady discoveries (4) made polysomnography, with its ability to perform simultaneous whole night recordings of EEG, electromyogram (EMG), and electrooculogram (EOC), a major diagnostic tool in study of sleep disorders. This facility has been of further critical importance in allowing evaluation of the interaction between sleep and changes in hemodynamics and autonomic cardiovascular control. Consequently the

  15. 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.

  16. 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.

  17. Phylogeny of Trypanosoma brucei and Trypanosoma evansi in naturally infected cattle in Nigeria by analysis of repetitive and ribosomal DNA sequences.

    Science.gov (United States)

    Takeet, Michael I; Peters, Sunday O; Fagbemi, Benjamin O; De Donato, Marcos; Takeet, Vivian O; Wheto, Mathew; Imumorin, Ikhide G

    2016-08-01

    In continuing efforts to better understand the genetics of bovine trypanosomosis, we assessed genetic diversity of Trypanosoma brucei and Trypanosoma evansi in naturally infected Nigerian cattle using repetitive DNA and internal transcribed spacer 1 of rDNA sequences and compared these sequences to species from other countries. The length of repetitive DNA sequences in both species ranged from 161 to 244 bp and 239 to 240 bp for T. brucei and T. evansi, respectively, while the ITS1 rDNA sequences length range from 299 to 364 bp. The mean GC content of ITS1 rDNA sequences was 33.57 %, and that of repetitive sequences were 39.9 and 31.1 % for T. brucei and T. evansi, respectively. Result from sequence alignment revealed both T. brucei and T. evansi repetitive DNA sequences to be more polymorphic than ITS1 rDNA sequences, with moderate points of deletion and insertions. T. brucei separated into two clades when subjected to phylogenetic analysis. T. evansi repetitive DNA sequences clustered tightly within the T. brucei clade while the ITS1 rDNA sequences of T. brucei were clearly separated from T. theileri and T. vivax individually used as outgroups. This study suggest that ITS1 rDNA sequences may not be suitable for phylogenetic differentiation of the Trypanozoon group and also suggest that T. evansi may be a phenotypic variant of T. brucei which may have potential implications in designing prevention and therapeutic strategies.

  18. The contribution of chromosomal translocations to antigenic variation in Trypanosoma brucei.

    Science.gov (United States)

    Van der Ploeg, L H; Cornelissen, A W

    1984-11-13

    Genomic rearrangements influencing gene expression occur throughout nature. Several of these rearrangements disrupt normal gene expression, as exemplified by the genetic alterations caused by the mobile genetic elements of maize or Drosophila (see Shapiro 1983). Other rearrangements are part of the normal developmental programme of an organism. An understanding of the control of genomic rearrangements and their effects on gene expression should contribute to our insight into the mechanism of genetic programming and cellular development. The protozoan parasite Trypanosoma brucei exhibits a variety of genomic rearrangements that influence the expression of genes that code for versions of the variant surface glycoprotein (v.s.g.), which makes up the cell surface coat. V.s.g. genes are expressed in a mutually exclusive manner. Several v.s.g. genes are activated by duplicative transposition of the gene to a telomeric expression site where they are transcribed, while others can be activated without detectable genomic rearrangements. Recently we have been able to fractionate the chromosomes of T. brucei in agarose gels (Van der Ploeg et al. 1984 a). This led to the observations that duplicative transpositions occur inter-chromosomally and that the chromosomes of T. brucei are subject to frequent recombinations that displace hundreds of kilobase pairs. At least two and possibly more telomeric expression sites can be used for v.s.g. gene transcription. How these sites are activated and inactivated is still unsolved, but this does not depend on recombinations in the vicinity of the gene. Gross genomic rearrangements occur sometimes in correlation with antigenic switching and this suggests that such rearrangements have a function in regulating the mutually exclusive transcription of the different expression sites. V.s.g. genes consist of two exons. No physical linkage of the 35 nucleotide (n.t.) mini-exon to the v.s.g. gene main exon occurred within 15 kilobase pairs in

  19. SLEEP TIMING AND CIRCADIAN PHASE IN DELAYED SLEEP PHASE

    OpenAIRE

    2009-01-01

    Delayed sleep phase syndrome (DSPS) is a circadian rhythm sleep disorder in which the timing of the sleep episode occurs later than desired and is associated with difficulty falling asleep, problems awakening on time (e.g., to meet work or school obligations), and daytime sleepiness. The phase relationship between the timing of sleep and endogenous circadian rhythms is critical to the initiation and maintenance of sleep, and significant alteration leads to impairment of sleep quality and dura...

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

    OpenAIRE

    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...

  1. Sleep Hygiene and Sleep Quality in Italian and American Adolescents

    OpenAIRE

    2004-01-01

    This study investigated cross-cultural differences in adolescent sleep hygiene and sleep quality. Participants were 1348 students (655 males; 693 females) aged 12–17 years from public school systems in Rome, Italy (n = 776) and Southern Mississippi (n = 572). Participants completed the Adolescent Sleep-Wake Scale and the Adolescent Sleep Hygiene Scale. Reported sleep hygiene and sleep quality were significantly better for Italian than American adolescents. A moderate linear relationship was o...

  2. 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 (

  3. American Academy of Sleep Medicine

    Science.gov (United States)

    ... the field of sleep medicine. Join the American Academy of Sleep Medicine to further your career and ... MD Sept. 21 - As president of the American Academy of Sleep Medicine, I am keenly aware of ...

  4. Common Sleep Problems (For Teens)

    Science.gov (United States)

    ... sleep when a person has the most vivid dreams. Why Do Teens Have Trouble Sleeping? Research shows ... will look at your overall health and sleep habits. In addition to doing a physical examination, the ...

  5. Common Sleep Problems (For Teens)

    Science.gov (United States)

    ... Surgery? A Week of Healthy Breakfasts Shyness Common Sleep Problems KidsHealth > For Teens > Common Sleep Problems Print ... have emotional problems, like depression. What Happens During Sleep? You don't notice it, of course, but ...

  6. Sleep Changes in Older Adults

    Science.gov (United States)

    ... of the chemicals and hormones that help us sleep well (growth hormone and melatonin).Some lifestyle habits (such as smoking and drinking alcohol or caffeinated drinks) can cause sleep problems.Sleep problems may be caused by illness, ...

  7. Iii. Sleep assessment methods.

    Science.gov (United States)

    Sadeh, Avi

    2015-03-01

    Sleep is a complex phenomenon that could be understood and assessed at many levels. Sleep could be described at the behavioral level (relative lack of movements and awareness and responsiveness) and at the brain level (based on EEG activity). Sleep could be characterized by its duration, by its distribution during the 24-hr day period, and by its quality (e.g., consolidated versus fragmented). Different methods have been developed to assess various aspects of sleep. This chapter covers the most established and common methods used to assess sleep in infants and children. These methods include polysomnography, videosomnography, actigraphy, direct observations, sleep diaries, and questionnaires. The advantages and disadvantages of each method are highlighted.

  8. 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...

  9. Perspective on Sleep and Aging

    OpenAIRE

    Monjan, Andrew A.

    2010-01-01

    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 ar...

  10. Perspective on Sleep and Aging

    OpenAIRE

    Monjan, Andrew A.

    2010-01-01

    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 di...

  11. Sleep Deprivation and Neurobehavioral Dynamics

    OpenAIRE

    Basner, Mathias; Rao, Hengyi; Goel, Namni; David F. Dinges

    2013-01-01

    Lifestyles involving sleep deprivation are common, despite mounting evidence that both acute total sleep deprivation and chronically restricted sleep degrade neurobehavioral functions associated with arousal, attention, memory and state stability. Current research suggests dynamic differences in the way the central nervous system responds to acute versus chronic sleep restriction, which is reflected in new models of sleep-wake regulation. Chronic sleep restriction likely induces long-term neu...

  12. Stress, Sleep, and Allergy

    OpenAIRE

    Jernelöv, Susanna

    2010-01-01

    Allergic diseases have recently increased dramatically in the western world, now affecting about 30% of the Swedish population. The reasons for this increase are unclear, but some of the suspects are behavioral factors, such as stress and sleep. Problems with stress are also common today, and stress may change the set-points for the functioning of the body, for instance in the immune system. Sleep, on the other hand, is important for recuperation, and disturbed sleep acts a ...

  13. Isolated sleep paralysis

    OpenAIRE

    Sawant, Neena S.; Parkar, Shubhangi R.; Tambe, Ravindra

    2005-01-01

    Sleep paralysis (SP) is a cardinal symptom of narcolepsy. However, little is available in the literature about isolated sleep paralysis. This report discusses the case of a patient with isolated sleep paralysis who progressed from mild to severe SP over 8 years. He also restarted drinking alcohol to be able to fall asleep and allay his anxiety symptoms. The patient was taught relaxation techniques and he showed complete remission of the symptoms of SP on follow up after 8 months.

  14. Mapping replication dynamics in Trypanosoma brucei reveals a link with telomere transcription and antigenic variation.

    Science.gov (United States)

    Devlin, Rebecca; Marques, Catarina A; Paape, Daniel; Prorocic, Marko; Zurita-Leal, Andrea C; Campbell, Samantha J; Lapsley, Craig; Dickens, Nicholas; McCulloch, Richard

    2016-05-26

    Survival of Trypanosoma brucei depends upon switches in its protective Variant Surface Glycoprotein (VSG) coat by antigenic variation. VSG switching occurs by frequent homologous recombination, which is thought to require locus-specific initiation. Here, we show that a RecQ helicase, RECQ2, acts to repair DNA breaks, including in the telomeric site of VSG expression. Despite this, RECQ2 loss does not impair antigenic variation, but causes increased VSG switching by recombination, arguing against models for VSG switch initiation through direct generation of a DNA double strand break (DSB). Indeed, we show DSBs inefficiently direct recombination in the VSG expression site. By mapping genome replication dynamics, we reveal that the transcribed VSG expression site is the only telomeric site that is early replicating - a differential timing only seen in mammal-infective parasites. Specific association between VSG transcription and replication timing reveals a model for antigenic variation based on replication-derived DNA fragility.

  15. 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.

  16. Trypanosoma brucei Parasites Occupy and Functionally Adapt to the Adipose Tissue in Mice

    OpenAIRE

    Trindade, Sandra; Rijo-Ferreira, Filipa; Carvalho, Tânia; Pinto-Neves, Daniel; Guegan, Fabien; Aresta-Branco, Francisco; Bento, Fabio; Young, Simon A.; Pinto, Andreia; Van Den Abbeele, Jan; Ribeiro, Ruy M.; Dias, Sérgio; Smith, Terry K.; Figueiredo, Luisa M.

    2016-01-01

    This work was supported by 55007419 (HHMI) and 2151 (EMBO) to L.M.F., D.P.-N., F.B., and F.G.; FCT fellowships to S.T., F.R.-F., and F.A.-B. (SFRH/BPD/89833/2012, SFRH/BD/51286/2010, and SFRH/BD/80718/2011, respectively); Wellcome Trust grant (093228), MRC MR/M020118/1, and European Community Seventh Framework Programme under grant agreement No. 602773 (Project KINDRED) to S.A.Y. and T.K.S.; and PAI 7/41 (Belspo) and ERC-NANOSYM to J.V.D.A. Trypanosoma brucei is an extracellular parasite t...

  17. Contribution of Glucose Transport to the Control of the Glycolytic Flux in Trypanosoma brucei

    Science.gov (United States)

    Bakker, Barbara M.; Walsh, Michael C.; Ter Kuile, Benno H.; Mensonides, Femke I. C.; Michels, Paul A. M.; Opperdoes, Fred R.; Westerhoff, Hans V.

    1999-08-01

    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 transport activity independently of the glycolytic flux. Phloretin proved a competitive inhibitor. When the effect of the intracellular glucose concentration on the inhibition was taken into account, the flux control coefficient of the glucose transporter was between 0.3 and 0.5 at 5 mM glucose. Because the flux control coefficients of all steps in a metabolic pathway sum to 1, this result proves that glucose transport is not the rate-limiting step of trypanosome glycolysis. Under physiological conditions, transport shares the control with other steps. At glucose concentrations much lower than physiological, the glucose carrier assumed all control, in close agreement with model predictions.

  18. Nonepileptic paroxysmal sleep disorders.

    Science.gov (United States)

    Frenette, Eric; Guilleminault, Christian

    2013-01-01

    Events occurring during nighttime sleep in children can be easily mislabeled, as witnesses are usually not immediately available. Even when observers are present, description of the events can be sketchy, as these individuals are frequently aroused from their own sleep. Errors of perception are thus common and can lead to diagnosis of epilepsy where other sleep-related conditions are present, sometimes initiating unnecessary therapeutic interventions, especially with antiepileptic drugs. Often not acknowledged, paroxysmal nonepileptic behavioral and motor episodes in sleep are encountered much more frequently than their epileptic counterpart. The International Classification of Sleep Disorders (ICSD) 2nd edition displays an extensive list of such conditions that can be readily mistaken for epilepsy. The most prevalent ones are reviewed, such as nonrapid eye movement (NREM) sleep parasomnias, comprised of sleepwalking, confusional arousals and sleep terrors, periodic leg movements of sleep, repetitive movement disorders, benign neonatal myoclonus, and sleep starts. Apnea of prematurity is also briefly reviewed. Specific issues regarding management of these selected disorders, both for diagnostic consideration and for therapeutic intervention, are addressed.

  19. 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.

  20. Knockdown of Inner Arm Protein IC138 in Trypanosoma brucei Causes Defective Motility and Flagellar Detachment.

    Directory of Open Access Journals (Sweden)

    Corinne S Wilson

    Full Text Available Motility in the protozoan parasite Trypanosoma brucei is conferred by a single flagellum, attached alongside the cell, which moves the cell forward using a beat that is generated from tip-to-base. We are interested in characterizing components that regulate flagellar beating, in this study we extend the characterization of TbIC138, the ortholog of a dynein intermediate chain that regulates axonemal inner arm dynein f/I1. TbIC138 was tagged In situ-and shown to fractionate with the inner arm components of the flagellum. RNAi knockdown of TbIC138 resulted in significantly reduced protein levels, mild growth defect and significant motility defects. These cells tended to cluster, exhibited slow and abnormal motility and some cells had partially or fully detached flagella. Slight but significant increases were observed in the incidence of mis-localized or missing kinetoplasts. To document development of the TbIC138 knockdown phenotype over time, we performed a detailed analysis of flagellar detachment and motility changes over 108 hours following induction of RNAi. Abnormal motility, such as slow twitching or irregular beating, was observed early, and became progressively more severe such that by 72 hours-post-induction, approximately 80% of the cells were immotile. Progressively more cells exhibited flagellar detachment over time, but this phenotype was not as prevalent as immotility, affecting less than 60% of the population. Detached flagella had abnormal beating, but abnormal beating was also observed in cells with no flagellar detachment, suggesting that TbIC138 has a direct, or primary, effect on the flagellar beat, whereas detachment is a secondary phenotype of TbIC138 knockdown. Our results are consistent with the role of TbIC138 as a regulator of motility, and has a phenotype amenable to more extensive structure-function analyses to further elucidate its role in the control of flagellar beat in T. brucei.

  1. 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.

  2. Processing of the glycosomal matrix-protein import receptor PEX5 of Trypanosoma brucei

    Energy Technology Data Exchange (ETDEWEB)

    Gualdrón-López, Melisa [Research Unit for Tropical Diseases, de Duve Institute, Université catholique de Louvain, Brussels (Belgium); Michels, Paul A.M., E-mail: paul.michels@uclouvain.be [Research Unit for Tropical Diseases, de Duve Institute, Université catholique de Louvain, Brussels (Belgium)

    2013-02-01

    Highlights: ► Most eukaryotic cells have a single gene for the peroxin PEX5. ► PEX5 is sensitive to in vitro proteolysis in distantly related organisms. ► TbPEX5 undergoes N-terminal truncation in vitro and possibly in vivo. ► Truncated TbPEX5 is still capable of binding PTS1-containing proteins. ► PEX5 truncation is physiologically relevant or an evolutionary conserved artifact. -- Abstract: Glycolysis in kinetoplastid protists such as Trypanosoma brucei is compartmentalized in peroxisome-like organelles called glycosomes. Glycosomal matrix-protein import involves a cytosolic receptor, PEX5, which recognizes the peroxisomal-targeting signal type 1 (PTS1) present at the C-terminus of the majority of matrix proteins. PEX5 appears generally susceptible to in vitro proteolytic processing. On western blots of T. brucei, two PEX5 forms are detected with apparent M{sub r} of 100 kDa and 72 kDa. 5′-RACE-PCR showed that TbPEX5 is encoded by a unique transcript that can be translated into a protein of maximally 72 kDa. However, recombinant PEX5 migrates aberrantly in SDS–PAGE with an apparent M{sub r} of 100 kDa, similarly as observed for the native peroxin. In vitro protease susceptibility analysis of native and {sup 35}S-labelled PEX5 showed truncation of the 100 kDa form at the N-terminal side by unknown parasite proteases, giving rise to the 72 kDa form which remains functional for PTS1 binding. The relevance of these observations is discussed.

  3. Association between sleep hygiene and sleep quality in medical students.

    Science.gov (United States)

    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 demographics, sleep hygiene behaviors, and sleep quality. As hypothesized, medical students' sleep quality was significantly worse than a healthy adult normative sample (t = 5.13, p sleep quality in medical students was predicted by several demographic and sleep hygiene variables, and future research directions are proposed.

  4. 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...

  5. 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

  6. 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

    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

  7. Scanning and three-dimensional electron microscopy methods for the study of Trypanosoma brucei and Leishmania mexicana flagella.

    Science.gov (United States)

    Gluenz, Eva; Wheeler, Richard John; Hughes, Louise; Vaughan, Sue

    2015-01-01

    Three-dimensional electron microscopy tools have revolutionized our understanding of cell structure and molecular complexes in biology. Here, we describe methods for studying flagellar ultrastructure and biogenesis in two unicellular parasites-Trypanosoma brucei and Leishmania mexicana. We describe methods for the preparation of these parasites for scanning electron microscopy cellular electron tomography, and serial block face scanning electron microscopy (SBFSEM). These parasites have a highly ordered cell shape and form, with a defined positioning of internal cytoskeletal structures and organelles. We show how knowledge of these can be used to dissect cell cycles in both parasites and identify the old flagellum from the new in T. brucei. Finally, we demonstrate the use of SBFSEM three-dimensional models for analysis of individual whole cells, demonstrating the excellent potential this technique has for future studies of mutant cell lines.

  8. Inhibitors of the mitochondrial cytochrome b-c1 complex inhibit the cyanide-insensitive respiration of Trypanosoma brucei.

    Science.gov (United States)

    Turrens, J F; Bickar, D; Lehninger, A L

    1986-06-01

    The cyanide-insensitive respiration of bloodstream trypomastigote forms of Trypanosoma brucei (75 +/- 8 nmol O2 min-1(mg protein)-1) is completely inhibited by the mitochondrial ubiquinone-like inhibitors 2-hydroxy-3-undecyl-1,4-naphthoquinone (UHNQ) and 5-n-undecyl-6-hydroxy-4,7-dioxobenzothiazole (UHDBT). The Ki values for UHDBT (30 nM) and UHNQ (2 microM) are much lower than the reported Ki for salicylhydroxamic acid (SHAM) (5 microM), a widely used inhibitor of the cyanide-insensitive oxidase. UHNQ also stimulated the glycerol-3-phosphate-dependent reduction of phenazine methosulfate, demonstrating that the site of UHNQ inhibition is on the terminal oxidase of the cyanide-insensitive respiration of T. brucei. These results suggest that a ubiquinone-like compound may act as an electron carrier between the two enzymatic components of the cyanide-insensitive glycerol-3-phosphate oxidase.

  9. TbFlabarin, a flagellar protein of Trypanosoma brucei, highlights differences between Leishmania and Trypanosoma flagellar-targeting signals.

    Science.gov (United States)

    Tetaud, Emmanuel; Lefebvre, Michèle; M'Bang-Benet, Diane-Ethna; Crobu, Lucien; Blancard, Corinne; Sterkers, Yvon; Pages, Michel; Bastien, Patrick; Merlin, Gilles

    2016-07-01

    TbFlabarin is the Trypanosoma brucei orthologue of the Leishmania flagellar protein LdFlabarin but its sequence is 33% shorter than LdFlabarin, as it lacks a C-terminal domain that is indispensable for LdFlabarin to localize to the Leishmania flagellum. TbFlabarin is mainly expressed in the procyclic forms of the parasite and localized to the flagellum, but only when two palmitoylable cysteines at positions 3 and 4 are present. TbFlabarin is more strongly attached to the membrane fraction than its Leishmania counterpart, as it resists complete solubilization with as much as 0.5% NP-40. Expression ablation by RNA interference did not change parasite growth in culture, its morphology or apparent motility. Heterologous expression showed that neither TbFlabarin in L. amazonensis nor LdFlabarin in T. brucei localized to the flagellum, revealing non-cross-reacting targeting signals between the two species.

  10. 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). PMID:27471418

  11. 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.

  12. [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

  13. Comparative genomics reveals two novel RNAi factors in Trypanosoma brucei and provides insight into the core machinery.

    Directory of Open Access Journals (Sweden)

    Rebecca L Barnes

    Full Text Available The introduction ten years ago of RNA interference (RNAi as a tool for molecular exploration in Trypanosoma brucei has led to a surge in our understanding of the pathogenesis and biology of this human parasite. In particular, a genome-wide RNAi screen has recently been combined with next-generation Illumina sequencing to expose catalogues of genes associated with loss of fitness in distinct developmental stages. At present, this technology is restricted to RNAi-positive protozoan parasites, which excludes T. cruzi, Leishmania major, and Plasmodium falciparum. Therefore, elucidating the mechanism of RNAi and identifying the essential components of the pathway is fundamental for improving RNAi efficiency in T. brucei and for transferring the RNAi tool to RNAi-deficient pathogens. Here we used comparative genomics of RNAi-positive and -negative trypanosomatid protozoans to identify the repertoire of factors in T. brucei. In addition to the previously characterized Argonaute 1 (AGO1 protein and the cytoplasmic and nuclear Dicers, TbDCL1 and TbDCL2, respectively, we identified the RNA Interference Factors 4 and 5 (TbRIF4 and TbRIF5. TbRIF4 is a 3'-5' exonuclease of the DnaQ superfamily and plays a critical role in the conversion of duplex siRNAs to the single-stranded form, thus generating a TbAGO1-siRNA complex required for target-specific cleavage. TbRIF5 is essential for cytoplasmic RNAi and appears to act as a TbDCL1 cofactor. The availability of the core RNAi machinery in T. brucei provides a platform to gain mechanistic insights in this ancient eukaryote and to identify the minimal set of components required to reconstitute RNAi in RNAi-deficient parasites.

  14. 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.

  15. Trypanosoma brucei rhodesiense infection in a German traveller returning from the Masai Mara area, Kenya, January 2012.

    Science.gov (United States)

    Wolf, T; Wichelhaus, T; Gottig, S; Kleine, C; Brodt, H R; Just-Nuebling, G

    2012-03-08

    In January 2012, a case of Human African Trypanosomiasis (HAT) has been identified in Germany in a traveller returning from the Masai Mara area in Kenya. The 62-year-old man had travelled to the Masai Mara game park from 18 to 19 January 2012 and developed fever on 28 January. The infection with Trypanosoma brucei rhodesiense was confirmed by laboratory testing three days hereafter.

  16. 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

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: The novel chemotypes identified here could represent leads for future therapeutic development against the African trypanosome.

  17. Evolutionary consequences of a large duplication event in Trypanosoma brucei: Chromosomes 4 and 8 are partial duplicons

    Directory of Open Access Journals (Sweden)

    Jackson Andrew P

    2007-11-01

    Full Text Available Abstract Background Gene order along the genome sequence of the human parasite Trypanosoma brucei provides evidence for a 0.5 Mb duplication, comprising the 3' regions of chromosomes 4 and 8. Here, the principal aim was to examine the contribution made by this duplication event to the T. brucei genome sequence, emphasising the consequences for gene content and the evolutionary change subsequently experienced by paralogous gene copies. The duplicated region may be browsed online at http://www.genedb.org/genedb/tryp/48dup_image.jsp Results Comparisons of trypanosomatid genomes demonstrated widespread gene loss from each duplicon, but also showed that 47% of duplicated genes were retained on both chromosomes as paralogous loci. Secreted and surface-expressed genes were over-represented among retained paralogs, reflecting a bias towards important factors at the host-parasite interface, and consistent with a dosage-balance hypothesis. Genetic divergence in both coding and regulatory regions of retained paralogs was bimodal, with a deficit in moderately divergent paralogs; in particular, non-coding sequences were either conserved or entirely remodelled. The conserved paralogs included examples of remarkable sequence conservation, but also considerable divergence of both coding and regulatory regions. Sequence divergence typically displayed strong negative selection; but several features, such as asymmetric evolutionary rates, positively-selected codons and other non-neutral substitutions, suggested that divergence of some paralogs was driven by functional change. The absence of orthologs to retained paralogs in T. congolense indicated that the duplication event was specific to T. brucei. Conclusion The duplication of this chromosomal region doubled the dosage of many genes. Rather than creating 'more of the same', these results show that paralogs were structurally modified according to various evolutionary trajectories. The retention of paralogs, and

  18. Brain Basics: Understanding Sleep

    Science.gov (United States)

    ... their dreams – a rare, dangerous problem called REM sleep behavior disorder . A person dreaming about a ball game, ... bed awake : If you can't get to sleep, don't just lie in bed. Do something else, like reading, watching television, or listening to music, until you feel tired. ...

  19. 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…

  20. 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.

  1. 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.

    2008-01-01

    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

  2. Adenosine and sleep

    Energy Technology Data Exchange (ETDEWEB)

    Yanik, G.M. Jr.

    1987-01-01

    Behavioral and biochemical approaches have been used to determine the relative contribution of endogenous adenosine and adenosine receptors to the sleep-wake cycle in the rat. Adenosine concentrations in specific areas of the rat brain were not affected by 24 hours of total sleep deprivation, or by 24 or 48 hours of REM sleep deprivation. In order to assess the effect of REM sleep deprivation on adenosine A/sub 1/ receptors, /sup 3/H-L-PIA binding was measured. The Bmax values for /sup 3/H-L-PIA binding to membrane preparations of the cortices and corpus striata from 48 hour REM sleep-deprived animals were increased 14.8% and 23%, respectively. These increases were not maintained following the cessation of sleep deprivation and recovered within 2 hours. The results of a 96 hour REM deprivation experiment were similar to those of the 48 hour REM sleep deprivation experiment. However, these increases were not evident in similar structures taken from stress control animals, and conclusively demonstrated that the changes in /sup 3/H-L-PIA binding resulted from REM sleep deprivation and not from stress.

  3. 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

  4. 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 antidepressan

  5. Total sleep deprivation study in delayed sleep-phase syndrome

    Directory of Open Access Journals (Sweden)

    Md Dilshad Manzar

    2011-01-01

    Full Text Available Delayed sleep-phase syndrome (DSPS is characterized by delayed sleep onset against the desired clock time. It often presents with symptoms of sleep-onset insomnia or difficulty in awakening at the desired time. We report the finding of sleep studies after 24 h total sleep deprivation (TSD in a 28-year-old DSPS male patient. He had characteristics of mild chronic DSPS, which may have been precipitated by his frequent night shift assignments. The TSD improved the patients sleep latency and efficiency but all other sleep variables showed marked differences.

  6. 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.

  7. Circadian Rhythm Sleep Disorders

    Directory of Open Access Journals (Sweden)

    Erhan Akinci

    2016-06-01

    Full Text Available The circadian rhythm sleep disorders define the clinical conditions where sleep and ndash;wake rhythm is disrupted despite optimum environmental and social conditions. They occur as a result of the changes in endogenous circadian hours or non-compatibility of environmental factors or social life with endogenous circadian rhythm. The sleep and ndash;wake rhythm is disrupted continuously or in repeating phases depending on lack of balance between internal and external cycles. This condition leads to functional impairments which cause insomnia, excessive sleepiness or both in people. Application of detailed sleep anamnesis and sleep diary with actigraphy record, if possible, will be sufficient for diagnosis. The treatment aims to align endogenous circadian rhythm with environmental conditions. The purpose of this article is to review pathology, clinical characteristics, diagnosis and treatment of circadian rhythm disorder. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2016; 8(2: 178-189

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

    Directory of Open Access Journals (Sweden)

    Temidayo O Omobowale

    2015-01-01

    Full Text Available Introduction: The medicinal properties of Azadirachta indica have been harnessed for many years in the treatment of many diseases in both humans and animals. Materials and Methods: 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. Results: 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 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. Conclusion: From this study, MEAI showed significant ability to attenuate oxidative stress and inflammation during experimental T. brucei infection.

  9. 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.

  10. 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

  11. 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.

  12. Human African trypanosomiasis with 7-year incubation period: clinical, laboratory and neuroimaging findings.

    Science.gov (United States)

    Wengert, Oliver; Kopp, Marcel; Siebert, Eberhard; Stenzel, Werner; Hegasy, Guido; Suttorp, Norbert; Stich, August; Zoller, Thomas

    2014-06-01

    Human African trypanosomiasis (HAT), also referred to as "sleeping sickness", is caused by the parasite Trypanosoma brucei. Diagnosing imported HAT outside endemic areas is difficult and diagnosis is often delayed. We report a case of imported human African trypanosomiasis caused by Trypanosoma brucei gambiense with an unusually long incubation period of at least 7 years. A 33 year old male African patient, a former resident of Cameroon, presented with a 4-month history of progressive personality changes. A few weeks before presentation the patient had first been admitted to a psychiatric ward and received antidepressant treatment, until a lumbar puncture showed pleocytosis and then antibiotic treatment for suspected neuroborreliosis was initiated. The patient continued to deteriorate during antibiotic treatment and became increasingly lethargic. Under antiparasitic and anti-inflammatory treatment, the condition of the patient gradually improved over the following months and he recovered completely after 24 months of follow-up. This well-documented case illustrates typical difficulties in establishing the correct diagnosis outside endemic areas and provides an overview of typical clinical, neuropathological and neuroimaging findings in T. b. gambiense trypanosomiasis, guiding the clinician in establishing the correct diagnosis in this rare disease.

  13. Functional neuroimaging of sleep disorders.

    Science.gov (United States)

    Nofzinger, Eric A

    2008-01-01

    Functional neuroimaging methods provide a means to understand brain function in patients with sleep disorders. This paper summarizes functional neuroimaging findings in sleep disorders patients, and studies addressing the pharmacology of sleep and sleep disorders. Areas in which functional neuroimaging methods may be helpful in sleep medicine, and in which future development is advised, include: 1) clarification of pathophysiology; 2) aid in differential diagnosis; 3) assessment of treatment response; 4) guiding new drug development; and 5) monitoring treatment response.

  14. [Sleep disorders and their treatment].

    Science.gov (United States)

    Holsboer-Trachsler, E

    1995-04-11

    Disturbed or inadequate sleep is a frequent complaint, often with a chronic course, requiring adequate treatment. To choose an appropriate therapy it is necessary to develop a useful, reliable valid and specific diagnostic procedure. Primary care physicians can recognize and treat most sleep disorders. For special diagnostic cases sleep centers are recommended. Sleep disorders may be managed by adequate pharmacological as well as nonpharmacological treatments. Besides specific pharmacological interventions, education in sleep/wake hygiene and several psychotherapeutic strategies may be valuable.

  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.

  16. [Circadian rhythm sleep disorder].

    Science.gov (United States)

    Mishima, Kazuo

    2013-12-01

    Primary pathophysiology of circadian rhythm sleep disorders(CRSDs) is a misalignment between the endogenous circadian rhythm phase and the desired or socially required sleep-wake schedule, or dysfunction of the circadian pacemaker and its afferent/efferent pathways. CRSDs consist of delayed sleep phase type, advanced sleep phase type, free-running type, irregular sleep-wake type, shift work type and jet lag type. Chronotherapy using strong zeitgebers (time cues), such as bright light and melatonin/ melatonin type 2 receptor agonist, is effective when administered with proper timing. Bright light is the strongest entraining agent of circadian rhythms. Bright light therapy (appropriately-timed exposure to bright light) for CRSDs is an effective treatment option, and can shift the sleep-wake cycle to earlier or later times, in order to correct for misalignment between the circadian system and the desired sleep-wake schedule. Timed administration of melatonin, either alone or in combination with light therapy has also been shown to be useful in the treatment of CRSDs.

  17. Sleep, vigilance, and thermosensitivity.

    Science.gov (United States)

    Romeijn, Nico; Raymann, Roy J E M; Møst, Els; Te Lindert, Bart; Van Der Meijden, Wisse P; Fronczek, Rolf; Gomez-Herrero, German; Van Someren, Eus J W

    2012-01-01

    The regulation of sleep and wakefulness is well modeled with two underlying processes: a circadian and a homeostatic one. So far, the parameters and mechanisms of additional sleep-permissive and wake-promoting conditions have been largely overlooked. The present overview focuses on one of these conditions: the effect of skin temperature on the onset and maintenance of sleep, and alertness. Skin temperature is quite well suited to provide the brain with information on sleep-permissive and wake-promoting conditions because it changes with most if not all of them. Skin temperature changes with environmental heat and cold, but also with posture, environmental light, danger, nutritional status, pain, and stress. Its effect on the brain may thus moderate the efficacy by which the clock and homeostat manage to initiate or maintain sleep or wakefulness. The review provides a brief overview of the neuroanatomical pathways and physiological mechanisms by which skin temperature can affect the regulation of sleep and vigilance. In addition, current pitfalls and possibilities of practical applications for sleep enhancement are discussed, including the recent finding of impaired thermal comfort perception in insomniacs.

  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. Changes in blood sugar levels of rats experimentally infected withTrypanosoma brucei and treated with imidocarb dipropionate and diminazene aceturate

    Institute of Scientific and Technical Information of China (English)

    Nwoha Rosemary Ijeoma Ogechi; Omamegbe Joseph Omalathebu

    2016-01-01

    Objective:To determine the effect ofTrypanosoma brucei (T. brucei) on blood sugar level of infected rats. Methods: The experiment was done with 42 albino rats grouped into 3 groups of 14 members each. Group A was uninfected (control group), Group B was infected withT. brucei and treated with diminazene aceturate, and Group C was infected withT. brucei and treated with imidocarb dipropionate. Blood samples were collected from the media canthus of the experimental rats on Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 for the assessment of change in blood sugar levels. The blood sugar levels were determined with a glucometer (Accu-chek active serialNo.GN:10023338). Results: By 4 to 5 days post infection, there was a significant increase (P 0.05) was observed in the groups when compared with the control group till Day 12 of the experiment. Conclusions:T. brucei caused a significant increase in blood sugar of infected rats.

  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. Obstructive Sleep Apnea

    OpenAIRE

    Brass, Steven D.; Ho, Matthew L.

    2006-01-01

    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 o...

  2. 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.

  3. 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...

  4. National Sleep Foundation

    Science.gov (United States)

    ... Hebrew Hindi Hungarian Icelandic Indonesian Irish Italian Japanese Korean Latvian Lithuanian Macedonian Malay Maltese Norwegian Persian Polish ... Test your knowledge, take our symptom screener, and learn more about narcolepsy. Sleep and Melatonin It can ...

  5. 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...

  6. Sleep and Aging: Insomnia

    Science.gov (United States)

    ... Aging Insomnia Insomnia is the most common sleep complaint at any age. It affects almost half of ... A-Z | videos A-Z | training | about us | Customer Support | site map National Institute on Aging | U.S. ...

  7. 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.

  8. Do Fish Sleep?

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    Most fish can’t shut their eyes, so it’s easy to think they don’t sleep. But that’s like assuming humans don’t sleep because we can’t shut our ears to drown out sound. In fact, many species of fish take time out during the day or (more often) at night to enter a sleeplike stage. Some of these fish float in place, others lie on the bottom。

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Identification and characterization of an unusual class I myosin involved in vesicle traffic in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Diana Spitznagel

    Full Text Available Myosins are a multimember family of motor proteins with diverse functions in eukaryotic cells. African trypanosomes possess only two candidate myosins and thus represent a useful system for functional analysis of these motors. One of these candidates is an unusual class I myosin (TbMyo1 that is expressed at similar levels but organized differently during the life cycle of Trypanosoma brucei. This myosin localizes to the polarized endocytic pathway in bloodstream forms of the parasite. This organization is actin dependent. Knock down of TbMyo1 results in a significant reduction in endocytic activity, a cessation in cell division and eventually cell death. A striking morphological feature in these cells is an enlargement of the flagellar pocket, which is consistent with an imbalance in traffic to and from the surface. In contrast TbMyo1 is distributed throughout procyclic forms of the tsetse vector and a loss of approximately 90% of the protein has no obvious effects on growth or morphology. These results reveal a life cycle stage specific requirement for this myosin in essential endocytic traffic and represent the first description of the involvement of a motor protein in vesicle traffic in these parasites.

  14. Identification and characterization of an unusual class I myosin involved in vesicle traffic in Trypanosoma brucei.

    Science.gov (United States)

    Spitznagel, Diana; O'Rourke, John F; Leddy, Neal; Hanrahan, Orla; Nolan, Derek P

    2010-01-01

    Myosins are a multimember family of motor proteins with diverse functions in eukaryotic cells. African trypanosomes possess only two candidate myosins and thus represent a useful system for functional analysis of these motors. One of these candidates is an unusual class I myosin (TbMyo1) that is expressed at similar levels but organized differently during the life cycle of Trypanosoma brucei. This myosin localizes to the polarized endocytic pathway in bloodstream forms of the parasite. This organization is actin dependent. Knock down of TbMyo1 results in a significant reduction in endocytic activity, a cessation in cell division and eventually cell death. A striking morphological feature in these cells is an enlargement of the flagellar pocket, which is consistent with an imbalance in traffic to and from the surface. In contrast TbMyo1 is distributed throughout procyclic forms of the tsetse vector and a loss of approximately 90% of the protein has no obvious effects on growth or morphology. These results reveal a life cycle stage specific requirement for this myosin in essential endocytic traffic and represent the first description of the involvement of a motor protein in vesicle traffic in these parasites.

  15. The Role of Folate Transport in Antifolate Drug Action in Trypanosoma brucei*

    Science.gov (United States)

    Dewar, Simon; Sienkiewicz, Natasha; Ong, Han B.; Wall, Richard J.; Horn, David

    2016-01-01

    The aim of this study was to identify and characterize mechanisms of resistance to antifolate drugs in African trypanosomes. Genome-wide RNAi library screens were undertaken in bloodstream form Trypanosoma brucei exposed to the antifolates methotrexate and raltitrexed. In conjunction with drug susceptibility and folate transport studies, RNAi knockdown was used to validate the functions of the putative folate transporters. The transport kinetics of folate and methotrexate were further characterized in whole cells. RNA interference target sequencing experiments identified a tandem array of genes encoding a folate transporter family, TbFT1–3, as major contributors to antifolate drug uptake. RNAi knockdown of TbFT1–3 substantially reduced folate transport into trypanosomes and reduced the parasite's susceptibly to the classical antifolates methotrexate and raltitrexed. In contrast, knockdown of TbFT1–3 increased susceptibly to the non-classical antifolates pyrimethamine and nolatrexed. Both folate and methotrexate transport were inhibited by classical antifolates but not by non-classical antifolates or biopterin. Thus, TbFT1–3 mediates the uptake of folate and classical antifolates in trypanosomes, and TbFT1–3 loss-of-function is a mechanism of antifolate drug resistance. PMID:27703008

  16. Crystal structures and inhibition of Trypanosoma brucei hypoxanthine–guanine phosphoribosyltransferase

    Science.gov (United States)

    Terán, David; Hocková, Dana; Česnek, Michal; Zíková, Alena; Naesens, Lieve; Keough, Dianne T.; Guddat, Luke W.

    2016-01-01

    Human African Trypanosomiasis (HAT) is a life-threatening infectious disease caused by the protozoan parasite, Trypanosoma brucei (Tbr). Due to the debilitating side effects of the current therapeutics and the emergence of resistance to these drugs, new medications for this disease need to be developed. One potential new drug target is 6-oxopurine phosphoribosyltransferase (PRT), an enzyme central to the purine salvage pathway and whose activity is critical for the production of the nucleotides (GMP and IMP) required for DNA/RNA synthesis within this protozoan parasite. Here, the first crystal structures of this enzyme have been determined, these in complex with GMP and IMP and with three acyclic nucleoside phosphonate (ANP) inhibitors. The Ki values for GMP and IMP are 30.5 μM and 77 μM, respectively. Two of the ANPs have Ki values considerably lower than for the nucleotides, 2.3 μM (with guanine as base) and 15.8 μM (with hypoxanthine as base). The crystal structures show that when two of the ANPs bind, they induce an unusual conformation change to the loop where the reaction product, pyrophosphate, is expected to bind. This and other structural differences between the Tbr and human enzymes suggest selective inhibitors for the Tbr enzyme can be designed. PMID:27786284

  17. Melarsoprol- and pentamidine-resistant Trypanosoma brucei rhodesiense populations and their cross-resistance.

    Science.gov (United States)

    Bernhard, Sonja C; Nerima, Barbara; Mäser, Pascal; Brun, Reto

    2007-11-01

    Resistance to melarsoprol and pentamidine was induced in bloodstream-form Trypanosoma brucei rhodesiense STIB 900 in vitro, and drug sensitivity was determined for melarsoprol, pentamidine and furamidine. The resistant populations were also inoculated into immunosuppressed mice to verify infectivity and to monitor whether rodent passage selects for clones with altered drug sensitivity. After proliferation in the mouse, trypanosomes were isolated and their IC(50) values to the three drugs were determined. To assess the stability of drug-induced resistance, drug pressure was ceased for 2 months and the drug sensitivity was determined again. Resistance was stable, with a few exceptions that are discussed. Drug IC(50)s indicated cross-resistance among all drugs, but to varying extents: resistance of the melarsoprol-selected and pentamidine-selected trypanosomes to pentamidine was the same, but the pentamidine-selected trypanosome population showed lower resistance to melarsoprol than the melarsoprol-selected trypanosomes. Interestingly, both resistant populations revealed the same intermediate cross-resistance to furamidine. Resistant trypanosome populations were characterised by molecular means, referring to the status of the TbAT1 gene. The melarsoprol-selected population apparently had lost TbAT1, whereas in the pentamidine-selected trypanosome population it was still present.

  18. Association of a novel preribosomal complex in Trypanosoma brucei determined by fluorescence resonance energy transfer.

    Science.gov (United States)

    Wang, Lei; Ciganda, Martin; Williams, Noreen

    2013-02-01

    We have previously reported that the trypanosome-specific proteins P34 and P37 form a unique preribosomal complex with ribosomal protein L5 and 5S rRNA in the nucleoplasm. We hypothesize that this novel trimolecular complex is necessary for stabilizing 5S rRNA in Trypanosoma brucei and is essential for the survival of the parasite. In vitro quantitative analysis of the association between the proteins L5 and P34 is fundamental to our understanding of this novel complex and thus our ability to exploit its unique characteristics. Here we used in vitro fluorescence resonance energy transfer (FRET) to analyze the association between L5 and P34. First, we demonstrated that FRET can be used to confirm the association between L5 and P34. We then determined that the binding constant for L5 and P34 is 0.60 ± 0.03 μM, which is in the range of protein-protein binding constants for RNA binding proteins. In addition, we used FRET to identify the critical regions of L5 and P34 involved in the protein-protein association. We found that the N-terminal APK-rich domain and RNA recognition motif (RRM) of P34 and the L18 domain of L5 are important for the association of the two proteins with each other. These results provide us with the framework for the discovery of ways to disrupt this essential complex.

  19. Parasite development and host responses during the establishment of Trypanosoma brucei infection transmitted by tsetse fly.

    Science.gov (United States)

    Barry, J D; Emergy, D L

    1984-02-01

    Following inoculation of Trypanosoma brucei into large mammals by the tsetse fly a local skin reaction, the 'chancre', develops due to trypanosome proliferation. We have cannulated the afferent and efferent lymphatics of the draining lymph node in goats and examined the onset of a cellular reaction, the emigration of the parasite from the chancre and the development of both antigenic variation and the specific immune response. The chancre first became detectable by day 3 post-infection, peaked by day 6 and then subsided. Lymphocyte output increased 6- to 8-fold by day 10 and the number of lymphoblasts increased 50-fold in this period. Both then declined. Trypanosomes were detected in lymph 1-2 days before the chancre, peaked by days 5-6, declined during development of the chancre and then peaked again. The bloodstream population appeared by days 4-5 and displayed different kinetics from that in lymph. Recirculation of parasites through the lymphatics ensued. Lymph-borne trypanosome populations were highly pleomorphic. Parasites in lymph expressed firstly a mixture of the Variable Antigen Types (VATs) which are found characteristically in the tsetse fly, this being followed by a mixture of other VATs. The two groups overlapped in appearance. In the bloodstream the same sequence of events occurred although 2 or 3 days later. The specific antibody response, as measured by radioimmunoassay and agglutination, arose within a few days of the first detection of each VAT. Activities appeared first in the lymph and then in plasma.

  20. Synchronous expression of individual metacyclic variant surface glycoprotein genes in Trypanosoma brucei.

    Science.gov (United States)

    Ramey-Butler, Kiantra; Ullu, Elisabetta; Kolev, Nikolay G; Tschudi, Christian

    2015-01-01

    One distinctive feature of the Trypanosoma brucei life cycle is the presence of two discrete populations that are based on differential expression of variant surface glycoproteins (VSGs). Both are adapted to the environmental pressures they face and more importantly, both contribute directly to transmission. Metacyclics in the tsetse fly enable transmission to a new mammalian host, whereas bloodstream trypanosomes must avoid immune destruction to the extent that sufficient numbers are available for transmission, when the insect vector takes a blood meal. At present, there are few investigations on the molecular aspects of parasite biology in the tsetse vector and specifically about the activation of metacyclic VSG gene expression. Here we used an established in vitro differentiation system based on the overexpression of the RNA-binding protein 6 (RBP6), to monitor two metacyclic VSGs (VSG 397 and VSG 653) during development from procyclics to infectious metacyclic forms. We observed that activation of these two mVSGs was simultaneous both at the transcript and protein level, and manifested by the appearance of only one of the mVSGs in individual cells.

  1. Identification of a new EF-hand superfamily member from Trypanosoma brucei

    Science.gov (United States)

    Wong, S.; Kretsinger, R. H.; Campbell, D. A.

    1992-01-01

    We identified several open reading frames between the regions encoding calmodulin and ubiquitin-EP52/1 in the genome of Trypanosoma brucei. One of these, EFH5, encodes a protein 192 amino acids long. The EFH5 transcript is present in poly(A)+ mRNA and is present at similar levels in the mammalian bloodstream form and the insect procyclic form. EFH5 contains four EF-hand homolog domains, two of which are inferred to bind Ca2+ ions. We expressed EFH5 as a fusion protein in Escherichia coli and demonstrated calcium-binding activity of the fusion protein using the 45Ca-overlay technique. The function of EFH5 remains unknown; however, as the fourth EF-hand homolog identified in trypanosomes, it attests to the broad range of functions assumed by calcium functioning as a second messenger. EFH5, which is most closely related to LAV1-2 from Physarum, represents a distinct subfamily among the EF-hand-containing proteins.

  2. Rediscovery of Trypanosoma (Pycnomonas) suis, a tsetse-transmitted trypanosome closely related to T. brucei.

    Science.gov (United States)

    Hutchinson, Rachel; Gibson, Wendy

    2015-12-01

    The African tsetse-transmitted trypanosomes are considered to be a well-known group of parasitic protozoa, but in 2008 a novel and distinctive trypanosome related to Trypanosoma brucei was discovered among tsetse isolates from Msubugwe in Tanzania. The host range, distribution and potential pathogenicity of this new trypanosome remain to be elucidated; such studies would be facilitated by a sensitive and specific identification method. Here, we identified two highly repetitive elements in the genome of the new trypanosome: a 177 bp repeat, which was located predominantly on the highly abundant minichromosomes, and a 138 bp repeat, which was widely dispersed in the genome. A PCR test based on each repeat was specific for the new trypanosome and sensitive to Trypanosoma (Pycnomonas) suis. We also present data on the molecular karyotype and spliced leader (SL, miniexon) repeat of the new trypanosome, both of which distinguish T. suis from other, better-known African tsetse-transmitted trypanosomes. The rediscovery of T. suis opens new lines of research into the evolution and biology of the African trypanosomes.

  3. Sleep Patterns in Children with Cystic Fibrosis

    OpenAIRE

    Meltzer, Lisa J.; Beck, Suzanne E.

    2012-01-01

    This study examined sleep patterns and the association between sleep and perceived health for children with and without CF. Ninety families (45 CF) completed questionnaires about the child’s sleep and health. Significant group differences were found for sleep patterns (bedtime, wake time, total sleep time), symptoms of sleep disordered breathing, and sleep disturbances. Poorer perceived health was associated with sleep disturbances among children with CF, but not for children without CF. This...

  4. 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.

  5. Obstructive sleep apnea.

    Science.gov (United States)

    Ho, Matthew L; Brass, Steven D

    2011-11-29

    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.

  6. 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.

  7. Obstructive sleep apnea alters sleep stage transition dynamics.

    Directory of Open Access Journals (Sweden)

    Matt T Bianchi

    Full Text Available INTRODUCTION: 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. METHODS AND PRINCIPAL FINDINGS: 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. CONCLUSION AND SIGNIFICANCE: 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.

  8. 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.

  9. Adenosine, Energy Metabolism, and Sleep

    Directory of Open Access Journals (Sweden)

    Tarja Porkka-Heiskanen

    2003-01-01

    Full Text Available While the exact function of sleep remains unknown, it is evident that sleep was developed early in phylogenesis and represents an ancient and vital strategy for survival. Several pieces of evidence suggest that the function of sleep is associated with energy metabolism, saving of energy, and replenishment of energy stores. Prolonged wakefulness induces signs of energy depletion in the brain, while experimentally induced, local energy depletion induces increase in sleep, similarly as would a period of prolonged wakefulness. The key molecule in the induction of sleep appears to be adenosine, which induces sleep locally in the basal forebrain.

  10. Decrease in monocular sleep after sleep deprivation in the domestic chicken

    NARCIS (Netherlands)

    Boerema, AS; Riedstra, B; Strijkstra, AM

    2003-01-01

    We investigated the trade-off between sleep need and alertness, by challenging chickens to modify their monocular sleep. We sleep deprived domestic chickens (Gallus domesticus) to increase their sleep need. We found that in response to sleep deprivation the fraction of monocular sleep within sleep d

  11. Altered sleep composition after traumatic brain injury does not affect declarative sleep-dependent memory consolidation

    OpenAIRE

    Janna eMantua; Keenan M Mahan; Owen S Henry; Rebecca M. C. Spencer

    2015-01-01

    Individuals with a history of traumatic brain injury (TBI) often report sleep disturbances, which may be caused by changes in sleep architecture or reduced sleep quality (greater time awake after sleep onset, poorer sleep efficiency, and sleep stage proportion alterations). Sleep is beneficial for memory formation, and herein we examine whether altered sleep physiology following TBI has deleterious effects on sleep-dependent declarative memory consolidation. Participants learned a list of wor...

  12. 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.

  13. Sleep timing and circadian phase in delayed sleep phase syndrome.

    Science.gov (United States)

    Chang, Anne-Marie; Reid, Kathryn J; Gourineni, Ramadevi; Zee, Phyllis C

    2009-08-01

    Delayed sleep phase syndrome (DSPS) is a circadian rhythm sleep disorder in which the timing of the sleep episode occurs later than desired and is associated with difficulty falling asleep, problems awakening on time (e.g., to meet work or school obligations), and daytime sleepiness. The phase relationship between the timing of sleep and endogenous circadian rhythms is critical to the initiation and maintenance of sleep, and significant alteration leads to impairment of sleep quality and duration. The aim of this retrospective study was to determine the phase relationship between sleep-wake times and physiological markers of circadian timing in clinic patients with DSPS. Objective and subjective measures of sleep timing and circadian phase markers (core body temperature and melatonin) were measured in patients with DSPS and compared with age-matched controls. As expected, significant delays in the timing of the major sleep episode and circadian phase of body temperature and melatonin rhythms were seen in the DSPS group when allowed to sleep at their own habitual schedules, but the phase relationship between sleep-wake times and circadian phase was similar between the 2 groups. These results suggest that the symptoms of insomnia and excessive daytime sleepiness in DSPS patients living under entrained real-life conditions cannot be explained by an alteration in the phase relationship between sleep-wake patterns and other physiological circadian rhythms.

  14. Introduction to modern sleep technology

    CERN Document Server

    Chiang, Rayleigh Ping-Ying

    2012-01-01

    This book offers a wide range of up-to-date insight on current research in sleep technology, covering advances in sleep medicine, clinical psychology, engineering, industrial design and technology management, all with the aim of improving people's daily lives.

  15. Sleep deprivation and false memories.

    Science.gov (United States)

    Frenda, Steven J; Patihis, Lawrence; Loftus, Elizabeth F; Lewis, Holly C; Fenn, Kimberly M

    2014-09-01

    Many studies have investigated factors that affect susceptibility to false memories. However, few have investigated the role of sleep deprivation in the formation of false memories, despite overwhelming evidence that sleep deprivation impairs cognitive function. We examined the relationship between self-reported sleep duration and false memories and the effect of 24 hr of total sleep deprivation on susceptibility to false memories. We found that under certain conditions, sleep deprivation can increase the risk of developing false memories. Specifically, sleep deprivation increased false memories in a misinformation task when participants were sleep deprived during event encoding, but did not have a significant effect when the deprivation occurred after event encoding. These experiments are the first to investigate the effect of sleep deprivation on susceptibility to false memories, which can have dire consequences.

  16. Rodent models of sleep apnea.

    Science.gov (United States)

    Davis, Eric M; O'Donnell, Christopher P

    2013-09-15

    Rodent models of sleep apnea have long been used to provide novel insight into the generation and predisposition to apneas as well as to characterize the impact of sleep apnea on cardiovascular, metabolic, and psychological health in humans. Given the significant body of work utilizing rodent models in the field of sleep apnea, the aims of this review are three-fold: first, to review the use of rodents as natural models of sleep apnea; second, to provide an overview of the experimental interventions employed in rodents to simulate sleep apnea; third, to discuss the refinement of rodent models to further our understanding of breathing abnormalities that occur during sleep. Given mounting evidence that sleep apnea impairs cognitive function, reduces quality of life, and exacerbates the course of multiple chronic diseases, rodent models will remain a high priority as a tool to interrogate both the pathophysiology and sequelae of breathing related abnormalities during sleep and to improve approaches to diagnosis and therapy.

  17. Sleep in High Stress Occupations

    Science.gov (United States)

    Flynn-Evans, Erin

    2014-01-01

    High stress occupations are associated with sleep restriction, circadian misalignment and demanding workload. This presentation will provide an overview of sleep duration, circadian misalignment and fatigue countermeasures and performance outcomes during spaceflight and commercial aviation.

  18. Sleep stages, memory and learning.

    OpenAIRE

    Dotto, L

    1996-01-01

    Learning and memory can be impaired by sleep loss during specific vulnerable "windows" for several days after new tasks have been learned. Different types of tasks are differentially vulnerable to the loss of different stages of sleep. Memory required to perform cognitive procedural tasks is affected by the loss of rapid-eye-movement (REM) sleep on the first night after learning occurs and again on the third night after learning. REM-sleep deprivation on the second night after learning does n...

  19. Sleep in thyrotoxicosis

    Directory of Open Access Journals (Sweden)

    G R Sridhar

    2011-01-01

    Full Text Available Objective: Pattern of sleep in hyperthyroid state / thyrotoxicosis has not been systematically studied. It is being characterized as poor without further elaboration. We analyzed the pattern of sleep in a large sample of individuals with thyrotoxicosis who came to our endocrine center in southern India. Materials and Methods: We identified individuals with the diagnosis of ′thyrotoxicosis′ from our electronic medical record database, and evaluated clinical parameters and pattern of their sleep: difficulty in falling asleep (DFA, difficulty in maintaining sleep (DMS, excess daytime sleepiness. In the first phase, univariate analysis with logistic regression was performed. Multivariate logistic regression was performed in the next phase on variables with a P-value < 0.1: these were considered as potential categories/ variables. Results: In model response variable with DFA, multivariate logistic regression predicted that subjects with abnormal appetite (more 1.7 or less 2.2, change in bowel motion (loose 1.5 or constipation 2.8, in mood (easy loss of temper 3.4, change of voice -- hoarse 7.4 or moderately hoarse 3.1, tended to have higher chances of difficulty in falling asleep (DFA. Patients with tremor (yes = 5.4 had greater likelihood of difficulty in maintaining sleep (DMS. Conclusions: Individuals with hyperthyroidism/thyrotoxicosis principally had difficulty in falling asleep DFA, which was related to hyperkinetic features.

  20. [Sleep related eating disorder].

    Science.gov (United States)

    Inoue, Yuichi; Komada, Yoko

    2010-01-01

    Nighttime eating is categorized as either sleep-related eating disorder (SRED) or night eating syndrome (NES). Critical reviews of the literature on both disorders have suggested that they are situated at opposite poles of a disordered eating spectrum. The feeding behavior in SRED is characterized by recurrent episodes of eating after an arousal from nighttime sleep with amnesia. Conversely, NES could be considered as an abnormality in the circadian rhythm of meal timing with a normal circadian timing of sleep onset. Both conditions clearly concentrate to occur during young adulthood, and are often relentless and chronic. Misunderstanding and low awareness of SRED and NES have limited our ability to determine the exact prevalence of the two disorders. SRED is frequently associated with other sleep disorders, in particular parasomnias such as sleep walking. Cognitive-behavioral therapy is ineffective, but pharmacotherapy is very effective in controlling SRED. Especially, studies have shown that the anti-seizure medication topiramate may be an effective treatment for SRED.

  1. Starting a sleep center.

    Science.gov (United States)

    Epstein, Lawrence J; Valentine, Paul S

    2010-05-01

    The demand for sleep medicine services has grown tremendously during the last decade and will likely continue. To date, growth in demand has been met by growth in the number of new sleep centers. The need for more new centers will be dependent on market drivers that include increasing regulatory requirements, personnel shortages, integration of home sleep testing, changes in reimbursement, a shift in emphasis from diagnostics to treatment, and an increased consumer focus on sleep. The decision to open a new center should be based on understanding the market dynamics, completing a market analysis, and developing a business plan. The business plan should include an overview of the facility, a personnel and organizational structure, an evaluation of the business environment, a financial plan, a description of services provided, and a strategy for obtaining, managing, and extending a referral base. Implementation of the business plan and successful operation require ongoing planning and monitoring of operational parameters. The need for new sleep centers will likely continue, but the shifting market dynamics indicate a greater need for understanding the marketplace and careful planning.

  2. Sustained sleep fragmentation induces sleep homeostasis in mice

    KAUST Repository

    Baud, Maxime O.

    2015-04-01

    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.

  3. [Evaluation of sleep apnea syndromes].

    Science.gov (United States)

    Poirrier, R

    1993-01-01

    The evaluation of sleep apnea syndrome is based on polysomnography. Different sensor and recording techniques are reported. Some widely used neurophysiological and cardiorespiratory analysis criteria are proposed. Many sleep laboratories develop ambulatory and automatized methods for screening breathing disorders associated with sleep. The main principles of these approaches are briefly reviewed.

  4. Type 1 Diabetes and Sleep.

    Science.gov (United States)

    Farabi, Sarah S

    2016-02-01

    IN BRIEF In people with type 1 diabetes, sleep may be disrupted as a result of both behavioral and physiological aspects of diabetes and its management. This sleep disruption may negatively affect disease progression and development of complications. This review highlights key research findings regarding sleep in people with type 1 diabetes.

  5. Cutaneous warming promotes sleep onset.

    NARCIS (Netherlands)

    Raymann, R.J.E.M.; Swaab, D.F.; Someren, E.J.W. van

    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. This decline is mainly due to an increase in skin blood flow and consequently skin warmi

  6. Sleep disturbances and glucose homeostasis

    NARCIS (Netherlands)

    Barf, R. Paulien; Scheurink, Anton J.W.

    2011-01-01

    Sleep disturbances, induced by either lifestyle, shift work or sleeping disorders, have become more prevalent in our 24/7 Western society. Sleep disturbances are associated with impaired health including metabolic diseases such as obesity and type 2 diabetes. The question remains whether there is a

  7. Sleep Disorders, Epilepsy, and Autism

    Science.gov (United States)

    Malow, Beth A.

    2004-01-01

    The purpose of this review article is to describe the clinical data linking autism with sleep and epilepsy and to discuss the impact of treating sleep disorders in children with autism either with or without coexisting epileptic seizures. Studies are presented to support the view that sleep is abnormal in individuals with autistic spectrum…

  8. All about Sleep (For Parents)

    Science.gov (United States)

    ... is very important to kids' well-being. The link between a lack of sleep and a child's behavior isn't always obvious. ... 8- to 12-Month-Old Obstructive Sleep Apnea Sleep Problems in Teens Separation Anxiety Sleepwalking Nightmares Time for Bed? Taking the Bite ...

  9. Sleep-patterns, co-sleeping and parent's perception of sleep among school children: Comparison of domicile and gender

    OpenAIRE

    Ravi Gupta; Sunil Dutt Kandpal; Deepak Goel; Nidhi Mittal; Mohan Dhyani; Manish Mittal

    2016-01-01

    This study was aimed at assessment of sleep schedule, pre-sleep behavior, co-sleeping and parent’s perception of sleep of school going children. Method: Four schools each, from urban and rural area were included. Sleep patterns were assessed using the validated Hindi version of Childhood-Sleep-Habit-Questionnaire. Comparison was made between urban and rural group and between boys and girls. Interaction of gender, domicile and school-type was examined on the sleep patterns. Results: This...

  10. Structure and reactivity of Trypanosoma brucei pteridine reductase: inhibition by the archetypal antifolate methotrexate.

    Science.gov (United States)

    Dawson, Alice; Gibellini, Federica; Sienkiewicz, Natasha; Tulloch, Lindsay B; Fyfe, Paul K; McLuskey, Karen; Fairlamb, Alan H; Hunter, William N

    2006-09-01

    The protozoan Trypanosoma brucei has a functional pteridine reductase (TbPTR1), an NADPH-dependent short-chain reductase that participates in the salvage of pterins, which are essential for parasite growth. PTR1 displays broad-spectrum activity with pterins and folates, provides a metabolic bypass for inhibition of the trypanosomatid dihydrofolate reductase and therefore compromises the use of antifolates for treatment of trypanosomiasis. Catalytic properties of recombinant TbPTR1 and inhibition by the archetypal antifolate methotrexate have been characterized and the crystal structure of the ternary complex with cofactor NADP+ and the inhibitor determined at 2.2 A resolution. This enzyme shares 50% amino acid sequence identity with Leishmania major PTR1 (LmPTR1) and comparisons show that the architecture of the cofactor binding site, and the catalytic centre are highly conserved, as are most interactions with the inhibitor. However, specific amino acid differences, in particular the placement of Trp221 at the side of the active site, and adjustment of the beta6-alpha6 loop and alpha6 helix at one side of the substrate-binding cleft significantly reduce the size of the substrate binding site of TbPTR1 and alter the chemical properties compared with LmPTR1. A reactive Cys168, within the active site cleft, in conjunction with the C-terminus carboxyl group and His267 of a partner subunit forms a triad similar to the catalytic component of cysteine proteases. TbPTR1 therefore offers novel structural features to exploit in the search for inhibitors of therapeutic value against African trypanosomiasis.

  11. 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.

  12. Genome-wide dissection of the quorum sensing signalling pathway in Trypanosoma brucei.

    Science.gov (United States)

    Mony, Binny M; MacGregor, Paula; Ivens, Alasdair; Rojas, Federico; Cowton, Andrew; Young, Julie; Horn, David; Matthews, Keith

    2014-01-30

    The protozoan parasites Trypanosoma brucei spp. cause important human and livestock diseases in sub-Saharan Africa. In mammalian blood, two developmental forms of the parasite exist: proliferative 'slender' forms and arrested 'stumpy' forms that are responsible for transmission to tsetse flies. The slender to stumpy differentiation is a density-dependent response that resembles quorum sensing in microbial systems and is crucial for the parasite life cycle, ensuring both infection chronicity and disease transmission. This response is triggered by an elusive 'stumpy induction factor' (SIF) whose intracellular signalling pathway is also uncharacterized. Laboratory-adapted (monomorphic) trypanosome strains respond inefficiently to SIF but can generate forms with stumpy characteristics when exposed to cell-permeable cAMP and AMP analogues. Exploiting this, we have used a genome-wide RNA interference library screen to identify the signalling components driving stumpy formation. In separate screens, monomorphic parasites were exposed to 8-(4-chlorophenylthio)-cAMP (pCPT-cAMP) or 8-pCPT-2'-O-methyl-5'-AMP to select cells that were unresponsive to these signals and hence remained proliferative. Genome-wide Ion Torrent based RNAi target sequencing identified cohorts of genes implicated in each step of the signalling pathway, from purine metabolism, through signal transducers (kinases, phosphatases) to gene expression regulators. Genes at each step were independently validated in cells naturally capable of stumpy formation, confirming their role in density sensing in vivo. The putative RNA-binding protein, RBP7, was required for normal quorum sensing and promoted cell-cycle arrest and transmission competence when overexpressed. This study reveals that quorum sensing signalling in trypanosomes shares similarities to fundamental quiescence pathways in eukaryotic cells, its components providing targets for quorum-sensing interference-based therapeutics.

  13. A monoclonal antibody marker for the exclusion-zone filaments of Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Decossas Marion

    2008-07-01

    Full Text Available Abstract Background Trypanosoma brucei is a haemoflagellate pathogen of man, wild animals and domesticated livestock in central and southern Africa. In all life cycle stages this parasite has a single mitochondrion that contains a uniquely organised genome that is condensed into a flat disk-like structure called the kinetoplast. The kinetoplast is essential for insect form procyclic cells and therefore is a potential drug target. The kinetoplast is unique in nature because it consists of novel structural proteins and thousands of circular, interlocking, DNA molecules (kDNA. Secondly, kDNA replication is critically timed to coincide with nuclear S phase and new flagellum biogenesis. Thirdly, the kinetoplast is physically attached to the flagellum basal bodies via a structure called the tripartite attachment complex (TAC. The TAC consists of unilateral filaments (within the mitochondrion matrix, differentiated mitochondrial membranes and exclusion-zone filaments that extend from the distal end of the basal bodies. To date only one protein, p166, has been identified to be a component of the TAC. Results In the work presented here we provide data based on a novel EM technique developed to label and characterise cytoskeleton structures in permeabilised cells without extraction of mitochondrion membranes. We use this protocol to provide data on a new monoclonal antibody reagent (Mab 22 and illustrate the precise localisation of basal body-mitochondrial linker proteins. Mab 22 binds to these linker proteins (exclusion-zone filaments and provides a new tool for the characterisation of cytoskeleton mediated kinetoplast segregation. Conclusion The antigen(s recognised by Mab 22 are cytoskeletal, insensitive to extraction by high concentrations of non-ionic detergent, extend from the proximal region of basal bodies and bind to the outer mitochondrial membrane. This protein(s is the first component of the TAC exclusion-zone fibres to be identified. Mab 22

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

    Science.gov (United States)

    Yang, Lei; Lübeck, Mette; Ahring, Birgitte K; Lübeck, Peter S

    2016-02-01

    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 of the enzymes, pyruvate carboxylase (PYC), malate dehydrogenase (MDH), and fumarase (FUM), involved in the reductive tricarboxylic acid (rTCA) branch, were examined and compared in cells harvested from the acid production medium and a complete medium. The results showed that ambient pH had a significant impact 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 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 to an enhanced production of succinic acid in frd transformants compared with the wild-type in both pH buffered and pH non-buffered conditions with highest amount produced in the pH buffered condition (16.2 ± 0.5 g/L). This study demonstrates the feasibility of increasing succinic acid production through the cytosolic reductive pathway by genetic engineering in A. saccharolyticus.

  15. Psoriasis and Sleep Apnea

    DEFF Research Database (Denmark)

    Egeberg, Alexander; Khalid, Usman; Gislason, Gunnar Hilmar

    2015-01-01

    STUDY OBJECTIVES: Psoriasis and sleep apnea are associated with significant morbidity and mortality. Although both diseases have been linked with systemic inflammation, studies on their potential bidirectional association are lacking. We investigate the potential association between psoriasis...... and sleep apnea. METHODS: All Danish citizens age 18 y or older between January 1, 1997 and December 31, 2011 (n = 5,522,190) were linked at individual level in nationwide registries. Incidence rates (IRs) per 10,000 person-years were calculated and incidence rate ratios (IRRs) adjusted for age, sex......, socioeconomic status, smoking history, alcohol abuse, medication, and comorbidity were estimated by Poisson regression. RESULTS: There were 53,290, 6,885, 6,348, and 39,908 incident cases of mild psoriasis, severe psoriasis, psoriatic arthritis, and sleep apnea, respectively. IRRs (95% confidence interval...

  16. Psoriasis and Sleep Apnea

    DEFF Research Database (Denmark)

    Egeberg, Alexander; Khalid, Usman; Gislason, Gunnar Hilmar

    2016-01-01

    STUDY OBJECTIVES: Psoriasis and sleep apnea are associated with significant morbidity and mortality. Although both diseases have been linked with systemic inflammation, studies on their potential bidirectional association are lacking. We investigate the potential association between psoriasis...... and sleep apnea. METHODS: All Danish citizens age 18 y or older between January 1, 1997 and December 31, 2011 (n = 5,522,190) were linked at individual level in nationwide registries. Incidence rates (IRs) per 10,000 person-years were calculated and incidence rate ratios (IRRs) adjusted for age, sex......, socioeconomic status, smoking history, alcohol abuse, medication, and comorbidity were estimated by Poisson regression. RESULTS: There were 53,290, 6,885, 6,348, and 39,908 incident cases of mild psoriasis, severe psoriasis, psoriatic arthritis, and sleep apnea, respectively. IRRs (95% confidence interval...

  17. Sleep-related laryngospasm

    Directory of Open Access Journals (Sweden)

    Flavio S. Aloe

    1995-03-01

    Full Text Available Seven patients (mean age 46.6; range 33-58; 6M.1F presented with sleep-related choking episodes and were found to have features in common that distinguished them from other known causes of choking episodes during sleep. The characteristic features include: an awakening from sleep with an acute choking sensation, stridor, panic, tachycardia, short duration of episode Gess than 60 seconds, infrequent episodes (typically less than 1 per month, and absence of any known etiology. The disorder most commonly occurs in middle-aged males who are otherwise healthy. In one patient an episode of laryngospasm was polysomnographically documented to occur during stage 3. The clinical features and the polysomnographic findings suggest spasm of the vocal cords of unknown etiology.

  18. Optimizing sleep/wake schedules in space: Sleep during chronic nocturnal sleep restriction with and without diurnal naps

    Science.gov (United States)

    Mollicone, Daniel J.; Van Dongen, Hans P. A.; Dinges, David F.

    2007-02-01

    Effective sleep/wake schedules for space operations must balance severe time constraints with allocating sufficient time for sleep in order to sustain high levels of neurobehavioral performance. Developing such schedules requires knowledge about the relationship between scheduled "time in bed" (TIB) and actual physiological sleep obtained. A ground-based laboratory study in N=93 healthy adult subjects was conducted to investigate physiological sleep obtained in a range of restricted sleep schedules. Eighteen different conditions with restricted nocturnal anchor sleep, with and without diurnal naps, were examined in a response surface mapping paradigm. Sleep efficiency was found to be a function of total TIB per 24 h regardless of how the sleep was divided among nocturnal anchor sleep and diurnal nap sleep periods. The amounts of sleep stages 1+2 and REM showed more complex relationships with the durations of the anchor and nap sleep periods, while slow-wave sleep was essentially preserved among the different conditions of the experiment. The results of the study indicated that when sleep was chronically restricted, sleep duration was largely unaffected by whether the sleep was placed nocturnally or split between nocturnal anchor sleep periods and daytime naps. Having thus assessed that split-sleep schedules are feasible in terms of obtaining physiological sleep, further research will reveal whether these schedules and the associated variations in the distribution of sleep stages may be advantageous in mitigating neurobehavioral performance impairment in the face of limited time for sleep.

  19. Immediate postarousal sleep dynamics: an important determinant of sleep stability in obstructive sleep apnea.

    Science.gov (United States)

    Younes, Magdy; Hanly, Patrick J

    2016-04-01

    Arousability from sleep is increasingly recognized as an important determinant of the clinical spectrum of sleep disordered breathing (SDB). Patients with SDB display a wide range of arousability. The reason for these differences is not known. We hypothesized that differences in the speed with which sleep deepens following arousals/awakenings (postarousal sleep dynamics) is a major determinant of these differences in arousability in patients with SDB. We analyzed 40 preexisting clinical polysomnography records from patients with a range of SDB severity (apnea-hypopnea index 5-135/h). Sleep depth was determined every 3 s using the odds ratio product (ORP) method, a continuous index of sleep depth (0 = deep sleep, 2.5 = full wakefulness) that correlates strongly (r = 0.98) with arousability (Younes M, Ostrowski M, Soiferman M, Younes H, Younes M, Raneri J, and Hanly P. Sleep 38: 641-654, 2015). Time course of ORP was determined from end of arousal until the next arousal. All arousals were analyzed (142 ± 65/polysomnogram). ORP increased from 0.58 ± 0.32 during sleep to 1.67 ± 0.35 during arousals. ORP immediately (first 9 s) following arousals/awakenings (ORP-9) ranged from 0.21(very deep sleep) to 1.71 (highly arousable state) in different patients. In patients with high ORP-9, sleep deepened slowly (over minutes) beyond 9 s but only if no arousals/awakenings recurred. ORP-9 correlated strongly with average non-rapid eye movement sleep depth (r = 0.87, P sleep architecture. We conclude that postarousal sleep dynamics are highly variable among patients with sleep-disordered breathing and largely determine average sleep depth and continuity.

  20. Cetacean sleep: an unusual form of mammalian sleep.

    Science.gov (United States)

    Lyamin, Oleg I; Manger, Paul R; Ridgway, Sam H; Mukhametov, Lev M; Siegel, Jerome M

    2008-10-01

    Our knowledge of the form of lateralized sleep behavior, known as unihemispheric slow wave sleep (USWS), seen in all members of the order Cetacea examined to date, is described. We trace the discovery of this phenotypically unusual form of mammalian sleep and highlight specific aspects that are different from sleep in terrestrial mammals. We find that for cetaceans sleep is characterized by USWS, a negligible amount or complete absence of rapid eye movement (REM) sleep, and a varying degree of movement during sleep associated with body size, and an asymmetrical eye state. We then compare the anatomy of the mammalian somnogenic system with what is known in cetaceans, highlighting areas where additional knowledge is needed to understand cetacean sleep. Three suggested functions of USWS (facilitation of movement, more efficient sensory processing and control of breathing) are discussed. Lastly, the possible selection pressures leading to this form of sleep are examined, leading us to the suggestion that the selection pressure necessitating the evolution of cetacean sleep was most likely the need to offset heat loss to the water from birth and throughout life. Aspects such as sentinel functions and breathing are likely to be proximate evolutionary phenomenon of this form of sleep.

  1. Sleep and respiratory sleep disorders in idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Milioli, Giulia; Bosi, Marcello; Poletti, Venerino; Tomassetti, Sara; Grassi, Andrea; Riccardi, Silvia; Terzano, Mario Giovanni; Parrino, Liborio

    2016-04-01

    Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease (ILD) characterized by inflammation and progressive scarring of the lung parenchyma. IPF profoundly affects the quality of life (QoL) and fatigue is a frequently disabling symptom. The cause of fatigue is not well understood but patients with IPF often report extremely poor sleep quality and sleep-related breathing disorders (SRBD) that correlate with QoL. IPF patients present alterations in sleep architecture, including decreased sleep efficiency, slow wave sleep and rapid eye movement (REM) sleep, and increased sleep fragmentation. Moreover, sleep related hypoventilation during the vulnerable REM sleep period and obstructive sleep apnea-hypopnea syndrome (OSAHS) are frequent, but remain usually underdiagnosed. These SRBD in IPF are associated with alterations of the sleep structure, reduction of QoL and increased risk of mortality. In the absence of an effective therapy for IPF, optimizing the QoL could become the primary therapeutic goal. In this perspective the diagnosis and treatment of SRBD could significantly improve the QoL of IPF patients.

  2. Sleep paralysis and folklore.

    Science.gov (United States)

    Cox, Ann M

    2015-07-01

    Sleep paralysis is a relatively new term to describe what for hundreds of years many believed to be a visitation by a malevolent creature which attacked its victims as they slept. The first clinical description of sleep paralysis was published in 1664 in a Dutch physician's case histories, where it was referred to as, 'Incubus or the Night-Mare [sic]'. In 1977, it was discovered more than 100 previously healthy people from various South East Asian communities had died mysteriously in their sleep. The individuals affected were dying at a rate of 92/100,000 from Sudden Unexplained Nocturnal Death Syndrome. No underlying cause was ever found, only that subsequent studies revealed a high rate of sleep paralysis and belief in the dab tsog (nightmare spirit) amongst members of the community. The nightmare/succubus is descended from Lilith. The earliest reference to Lilith is found in the Sumerian King list of 2400 BC known as Lilitu or she-demon, she bore children from her nocturnal unions with men. In other derivations, she was Adam's first wife who rather than 'obey' became a demon that preyed on women during childbirth. In modern Middle Eastern maternity wards, some women still wear amulets for protection. Today, clinical cause of these disturbances is sleep paralysis due to the unsuitable timing of REM sleep. During the 'Nightmare' episode, the sleeper becomes partially conscious during REM cycle, leaving the individual in a state between dream and wakefulness. For some, culture and the tradition of the nightmare is explanation enough.

  3. Update of sleep alterations in depression

    OpenAIRE

    Andrés Barrera Medina; DeboraYoaly Arana Lechuga; Oscar Sánchez Escandón; Javier Velázquez Moctezuma

    2014-01-01

    Sleep disturbances in depression are up to 70%. Patients frequently have difficulty in falling asleep, frequent awakenings during the night and non-restorative sleep. Sleep abnormalities in depression are mainly characterized by increased rapid eye movement (REM) sleep and reduced slow wave sleep. Among the mechanisms of sleep disturbances in depression are hyperactivation of the hypothalamic-pituitary-adrenal axis, CLOCK gene polymorphism and primary sleep disorders. The habenula is a struct...

  4. Sleep disorders in cerebellar ataxias

    Directory of Open Access Journals (Sweden)

    José L. Pedroso

    2011-04-01

    Full Text Available Cerebellar ataxias comprise a wide range of etiologies leading to central nervous system-related motor and non-motor symptoms. Recently, a large body of evidence has demonstrated a high frequency of non-motor manifestations in cerebellar ataxias, specially in autosomal dominant spinocerebellar ataxias (SCA. Among these non-motor dysfunctions, sleep disorders have been recognized, although still under or even misdiagnosed. In this review, we highlight the main sleep disorders related to cerebellar ataxias focusing on REM sleep behavior disorder (RBD, restless legs syndrome (RLS, periodic limb movement in sleep (PLMS, excessive daytime sleepiness (EDS, insomnia and sleep apnea.

  5. [Sleep disorders: diagnosis and treatment].

    Science.gov (United States)

    Holsboer-Trachsler, E; Kocher, R

    1995-12-02

    Disturbed or inadequate sleep is a frequent complaint with a great impact on daily functions and an often chronic course requiring adequate treatment. To choose an appropriate therapy it is necessary to develop a useful, reliable, valid and specific diagnostic procedure. Primary care physicians can recognize and treat most sleep disorders. For special diagnostic cases sleep centers are recommended. Sleep disorders may be managed by adequate pharmacological as well as nonpharmacological treatment. Besides specific pharmacological means, education in sleep/wake physiology and hygiene and several psychotherapeutic strategies may be valuable.

  6. The F(0F(1-ATP synthase complex contains novel subunits and is essential for procyclic Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Alena Zíková

    2009-05-01

    Full Text Available The mitochondrial F(0F(1 ATP synthase is an essential multi-subunit protein complex in the vast majority of eukaryotes but little is known about its composition and role in Trypanosoma brucei, an early diverged eukaryotic pathogen. We purified the F(0F(1 ATP synthase by a combination of affinity purification, immunoprecipitation and blue-native gel electrophoresis and characterized its composition and function. We identified 22 proteins of which five are related to F(1 subunits, three to F(0 subunits, and 14 which have no obvious homology to proteins outside the kinetoplastids. RNAi silencing of expression of the F(1 alpha subunit or either of the two novel proteins showed that they are each essential for the viability of procyclic (insect stage cells and are important for the structural integrity of the F(0F(1-ATP synthase complex. We also observed a dramatic decrease in ATP production by oxidative phosphorylation after silencing expression of each of these proteins while substrate phosphorylation was not severely affected. Our procyclic T. brucei cells were sensitive to the ATP synthase inhibitor oligomycin even in the presence of glucose contrary to earlier reports. Hence, the two novel proteins appear essential for the structural organization of the functional complex and regulation of mitochondrial energy generation in these organisms is more complicated than previously thought.

  7. Complete coding sequence, sequence analysis and transmembrane topology modelling of Trypanosoma brucei rhodesiense putative oligosaccharyl transferase (TbOST II).

    Science.gov (United States)

    Baticados, Waren N; Inoue, Noboru; Sugimoto, Chihiro; Nagasawa, Hideyuki; Baticados, Abigail M

    2011-01-01

    The partial nucleotide sequence of putative Trypanosoma brucei rhodesiense oligosaccharyl transferase gene was previously reported. Here, we describe the determination of its full-length nucleotide sequence by Inverse PCR (IPCR), subsequent biological sequence analysis and transmembrane topology modelling. The full-length DNA sequence has an Open Reading Frame (ORF) of 2406 bp and encodes a polypeptide of 801 amino acid residues. Protein and DNA sequence analyses revealed that homologues within the genome of other kinetoplastid and various origins exist. Protein topology analysis predicted that Trypanosoma brucei rhodesiense putative oligosaccharyl transferase clone II (TbOST II) is a transmembrane protein with transmembrane helices in probably an N(cytosol)-C(cytosol) orientation. Data from the GenBank database assembly and sequence analyses in general clearly state that TbOST II is the STT3 subunit of OST in T.b. rhodesiense that necessitates further characterisation and functional studies with RNAi. TbOST II sequence had been deposited in the GenBank (accession number GU245937).

  8. 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.

  9. SAS-4 Protein in Trypanosoma brucei Controls Life Cycle Transitions by Modulating the Length of the Flagellum Attachment Zone Filament.

    Science.gov (United States)

    Hu, Huiqing; Zhou, Qing; Li, Ziyin

    2015-12-18

    The evolutionarily conserved centriole/basal body protein SAS-4 regulates centriole duplication in metazoa and basal body duplication in flagellated and ciliated organisms. Here, we report that the SAS-4 homolog in the flagellated protozoan Trypanosoma brucei, TbSAS-4, plays an unusual role in controlling life cycle transitions by regulating the length of the flagellum attachment zone (FAZ) filament, a specialized cytoskeletal structure required for flagellum adhesion and cell morphogenesis. TbSAS-4 is concentrated at the distal tip of the FAZ filament, and depletion of TbSAS-4 in the trypomastigote form disrupts the elongation of the new FAZ filament, generating cells with a shorter FAZ associated with a longer unattached flagellum and repositioned kinetoplast and basal body, reminiscent of epimastigote-like morphology. Further, we show that TbSAS-4 associates with six additional FAZ tip proteins, and depletion of TbSAS-4 disrupts the enrichment of these FAZ tip proteins at the new FAZ tip, suggesting a role of TbSAS-4 in maintaining the integrity of this FAZ tip protein complex. Together, these results uncover a novel function of TbSAS-4 in regulating the length of the FAZ filament to control basal body positioning and life cycle transitions in T. brucei.

  10. Deviating the level of proliferating cell nuclear antigen in Trypanosoma brucei elicits distinct mechanisms for inhibiting proliferation and cell cycle progression.

    Science.gov (United States)

    Valenciano, Ana L; Ramsey, Aaron C; Mackey, Zachary B

    2015-01-01

    The DNA replication machinery is spatially and temporally coordinated in all cells to reproduce a single exact copy of the genome per division, but its regulation in the protozoan parasite Trypanosoma brucei is not well characterized. We characterized the effects of altering the levels of proliferating cell nuclear antigen, a key component of the DNA replication machinery, in bloodstream form T. brucei. This study demonstrated that tight regulation of TbPCNA levels was critical for normal proliferation and DNA replication in the parasite. Depleting TbPCNA mRNA reduced proliferation, severely diminished DNA replication, arrested the synthesis of new DNA and caused the parasites to accumulated in G2/M. Attenuating the parasite by downregulating TbPCNA caused it to become hypersensitive to hydroxyurea. Overexpressing TbPCNA in T. brucei arrested proliferation, inhibited DNA replication and prevented the parasite from exiting G2/M. These results indicate that distinct mechanisms of cell cycle arrest are associated with upregulating or downregulating TbPCNA. The findings of this study validate deregulating intra-parasite levels of TbPCNA as a potential strategy for therapeutically exploiting this target in bloodstream form T. brucei.

  11. A proteomics approach reveals molecular manipulators of distinct cellular processes in the salivary glands of Glossina m. morsitans in response to Trypanosoma b. brucei infections

    NARCIS (Netherlands)

    Kariithi, Henry M.; Boeren, Sjef; Murungi, Edwin K.; Vlak, Just M.; Abd-Alla, Adly M.M.

    2016-01-01

    Background: Glossina m. morsitans is the primary vector of the Trypanosoma brucei group, one of the causative agents of African trypanosomoses. The parasites undergo metacyclogenesis, i.e. transformation into the mammalian-infective metacyclic trypomastigote (MT) parasites, in the salivary glands

  12. Identification and characterization of hundreds of potent and selective inhibitors of Trypanosoma brucei growth from a kinase-targeted library screening campaign.

    Directory of Open Access Journals (Sweden)

    Rosario Diaz

    2014-10-01

    Full Text Available In the interest of identification of new kinase-targeting chemotypes for target and pathway analysis and drug discovery in Trypanosomal brucei, a high-throughput screen of 42,444 focused inhibitors from the GlaxoSmithKline screening collection was performed against parasite cell cultures and counter-screened against human hepatocarcinoma (HepG2 cells. In this way, we have identified 797 sub-micromolar inhibitors of T. brucei growth that are at least 100-fold selective over HepG2 cells. Importantly, 242 of these hit compounds acted rapidly in inhibiting cellular growth, 137 showed rapid cidality. A variety of in silico and in vitro physicochemical and drug metabolism properties were assessed, and human kinase selectivity data were obtained, and, based on these data, we prioritized three compounds for pharmacokinetic assessment and demonstrated parasitological cure of a murine bloodstream infection of T. brucei rhodesiense with one of these compounds (NEU-1053. This work represents a successful implementation of a unique industrial-academic collaboration model aimed at identification of high quality inhibitors that will provide the parasitology community with chemical matter that can be utilized to develop kinase-targeting tool compounds. Furthermore these results are expected to provide rich starting points for discovery of kinase-targeting tool compounds for T. brucei, and new HAT therapeutics discovery programs.

  13. Identification and characterization of hundreds of potent and selective inhibitors of Trypanosoma brucei growth from a kinase-targeted library screening campaign.

    Science.gov (United States)

    Diaz, Rosario; Luengo-Arratta, Sandra A; Seixas, João D; Amata, Emanuele; Devine, William; Cordon-Obras, Carlos; Rojas-Barros, Domingo I; Jimenez, Elena; Ortega, Fatima; Crouch, Sabrinia; Colmenarejo, Gonzalo; Fiandor, Jose Maria; Martin, Jose Julio; Berlanga, Manuela; Gonzalez, Silvia; Manzano, Pilar; Navarro, Miguel; Pollastri, Michael P

    2014-10-01

    In the interest of identification of new kinase-targeting chemotypes for target and pathway analysis and drug discovery in Trypanosomal brucei, a high-throughput screen of 42,444 focused inhibitors from the GlaxoSmithKline screening collection was performed against parasite cell cultures and counter-screened against human hepatocarcinoma (HepG2) cells. In this way, we have identified 797 sub-micromolar inhibitors of T. brucei growth that are at least 100-fold selective over HepG2 cells. Importantly, 242 of these hit compounds acted rapidly in inhibiting cellular growth, 137 showed rapid cidality. A variety of in silico and in vitro physicochemical and drug metabolism properties were assessed, and human kinase selectivity data were obtained, and, based on these data, we prioritized three compounds for pharmacokinetic assessment and demonstrated parasitological cure of a murine bloodstream infection of T. brucei rhodesiense with one of these compounds (NEU-1053). This work represents a successful implementation of a unique industrial-academic collaboration model aimed at identification of high quality inhibitors that will provide the parasitology community with chemical matter that can be utilized to develop kinase-targeting tool compounds. Furthermore these results are expected to provide rich starting points for discovery of kinase-targeting tool compounds for T. brucei, and new HAT therapeutics discovery programs.

  14. 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 expres

  15. Memory consolidation in sleep disorders.

    Science.gov (United States)

    Cellini, Nicola

    2016-09-25

    In recent years sleep-related memory consolidation has become a central topic in the sleep research field. Several studies have shown that in healthy individuals sleep promotes memory consolidation. Notwithstanding this, the consequences of sleep disorders on offline memory consolidation remain poorly investigated. Research studies indicate that patients with insomnia, obstructive sleep apnea, and narcolepsy often exhibit sleep-related impairment in the consolidation of declarative and procedural information. On the other hand, patients with parasomnias, such as sleep-walking, night terrors and rapid eye movement (REM) behavior disorder, do not present any memory impairment. These studies suggest that only sleep disorders characterized by increased post-learning arousal and disrupted sleep architecture seem to be associated with offline memory consolidation issues. Such impairments, arising already in childhood, may potentially affect the development and maintenance of an individual's cognitive abilities, reducing their quality of life and increasing the risk of accidents. However, promising findings suggest that successfully treating sleep symptoms can result in the restoration of memory functions and marked reduction of direct and indirect societal costs of sleep disorders.

  16. Objective and subjective sleep quality

    DEFF Research Database (Denmark)

    Baandrup, Lone; Glenthøj, Birte Yding; Jennum, Poul Jørgen

    2016-01-01

    and subjective sleep quality during benzodiazepine discontinuation and whether sleep variables were associated with benzodiazepine withdrawal. Eligible patients included adults with a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder and long-term use of benzodiazepines in combination...... with antipsychotics. All participants gradually tapered the use of benzodiazepines after randomization to add-on treatment with melatonin versus placebo. Here we report a subsample of 23 patients undergoing sleep recordings (one-night polysomnography) and 55 patients participating in subjective sleep quality ratings....... Melatonin had no effect on objective sleep efficiency, but significantly improved self-reported sleep quality. Reduced benzodiazepine dosage at the 24-week follow-up was associated with a significantly decreased proportion of stage 2 sleep. These results indicate that prolonged-release melatonin has some...

  17. Sleep in trigeminal autonomic cephalagias

    DEFF Research Database (Denmark)

    Barløse, Mads; Lund, Nunu; Jensen, Rigmor Højland

    2014-01-01

    PURPOSE OF REVIEW: Sleep and cluster headache (CH) are believed to be interconnected but the precise relation to the other trigeminal autonomic cephalalgias (TACs) is uncertain and complex. A better understanding of these relations may eventually lead to a clarification of the underlying mechanisms...... and eventually to more effective therapeutic regimens. This review aims to evaluate the existing literature on the subject of TACs and sleep. An association between episodic CH and distinct macrostructural sleep phases, especially the relation to rapid eye movement (REM) sleep, has been described in some older...... studies but could not be confirmed in other, more recent studies. Investigations into the microstructure of sleep in these patients are lacking. Only a few case reports exist on the relation between sleep and other TACs. SUMMARY: Recent studies do not find an association between CH and REM sleep. One...

  18. Leo Tolstoy's theory of sleep.

    Science.gov (United States)

    Vein, Alla A

    2008-03-01

    Throughout his life, Leo Tolstoy was fascinated by the phenomena of sleep and dreams. He composed a series of observations and judgements that were brought together under "my theory of sleep". Tolstoy was constantly preoccupied with the basic principles of "the theory". It is hard to name a work by him where a description of sleep and/or a dream does not play a vital role in the unfolding of the plot. They testify to Tolstoy's interest in the mechanism of sleep and in the processes of falling asleep and waking up. Tolstoy viewed sleep as a specific state of consciousness, and he subsequently linked the concept of sleep with the concept of death. For him sleep and awakening were experiences emblematic of life and death.

  19. Interactions between sleep disorders and oral diseases.

    Science.gov (United States)

    Huynh, N T; Emami, E; Helman, J I; Chervin, R D

    2014-04-01

    Dental sleep medicine is a rapidly growing field that is in close and direct interaction with sleep medicine and comprises many aspects of human health. As a result, dentists who encounter sleep health and sleep disorders may work with clinicians from many other disciplines and specialties. The main sleep and oral health issues that are covered in this review are obstructive sleep apnea, chronic mouth breathing, sleep-related gastroesophageal reflux, and sleep bruxism. In addition, edentulism and its impact on sleep disorders are discussed. Improving sleep quality and sleep characteristics, oral health, and oral function involves both pathophysiology and disease management. The multiple interactions between oral health and sleep underscore the need for an interdisciplinary clinical team to manage oral health-related sleep disorders that are commonly seen in dental practice.

  20. Sleep on manned space flights: Zero gravity reduces sleep duration.

    Science.gov (United States)

    Gonfalone, Alain

    2016-12-01

    The success of a manned space mission depends on the well-being of the crew. Sleep in space has been the concern of researchers from the earliest days of manned space flight. In the new frontier of space exploration one of the great problems to be solved relates to sleep. Although many reports indicate that sleep in space differs only in minor ways from terrestrial sleep, such as being somewhat less comfortable, a consistent finding has been that sleep duration in space is shorter than that on the ground. This review considers the accumulating evidence that the main reason for the shorter duration of sleep in space is the absence of gravity. This evidence shows that, similar to the effect of many other environmental variables like light, sound and cold, gravity has a measurable impact on sleep structure. As opposed to ground, in zero gravity conditions the innate, permanent, and almost unconscious effort to maintain posture and equilibrium is reduced while simultaneously the vigilance against gravity or "the fear of falling" diminishes. These phenomena may potentially explain research findings that REM sleep latency and duration are shorter in space. This assumption also implies that sleep on ground is due in part to the effort to compensate for the presence of gravity and its effects on the posture and motion of the human body: an ignored and unsuspected contribution to sleep.

  1. Information processing during NREM sleep and sleep quality in insomnia.

    Science.gov (United States)

    Ceklic, Tijana; Bastien, Célyne H

    2015-12-01

    Insomnia sufferers (INS) are cortically hyperaroused during sleep, which seems to translate into altered information processing during nighttime. While information processing, as measured by event-related potentials (ERPs), during wake appears to be associated with sleep quality of the preceding night, the existence of such an association during nighttime has never been investigated. This study aims to investigate nighttime information processing among good sleepers (GS) and INS while considering concomitant sleep quality. Following a multistep clinical evaluation, INS and GS participants underwent 4 consecutive nights of PSG recordings in the sleep laboratory. Thirty nine GS (mean age 34.56±9.02) and twenty nine INS (mean age 43.03±9.12) were included in the study. ERPs (N1, P2, N350) were recorded all night on Night 4 (oddball paradigm) during NREM sleep. Regardless of sleep quality, INS presented a larger N350 amplitude during SWS (p=0.042) while GS showed a larger N350 amplitude during late-night stage 2 sleep (p=0.004). Regardless of diagnosis, those who slept objectively well showed a smaller N350 amplitude (p=0.020) while those who slept subjectively well showed a smaller P2 (pInformation processing seems to be associated with concomitant subjective and objective sleep quality for both GS and INS. However, INS show an alteration in information processing during sleep, especially for inhibition processes, regardless of their sleep quality.

  2. Genetics of human sleep behavioral phenotypes.

    Science.gov (United States)

    Hsu, Pei-Ken; Ptáček, Louis J; Fu, Ying-Hui

    2015-01-01

    Quality sleep is critical for daily functions of human beings and thus the timing and duration of sleep are tightly controlled. However, rare genetic variants affecting sleep regulatory mechanisms can result in sleep phenotypes of extremely deviated sleep/wake onset time or duration. Using genetic analyses in families with multiple members expressing particular sleep phenotypes, these sleep-associated genetic variants can be identified. Deciphering the nature of these genetic variants using animal models or biochemical methods helps further our understanding of sleep processes. In this chapter, we describe the methods for studying genetics of human sleep behavioral phenotypes.

  3. Sleep Disorders in Children

    Institute of Scientific and Technical Information of China (English)

    王迪秋

    2002-01-01

    All the parents want their children to go to bed by themselves and sleep through the night. Unluckily, over 30% of today--s parents do not have such children. Instead, their kids are awake at night crying or resist going to bed in the evening.

  4. Complex Sleep Apnea Syndrome

    Directory of Open Access Journals (Sweden)

    Muhammad Talha Khan

    2014-01-01

    Full Text Available Complex sleep apnea is the term used to describe a form of sleep disordered breathing in which repeated central apneas (>5/hour persist or emerge when obstructive events are extinguished with positive airway pressure (PAP and for which there is not a clear cause for the central apneas such as narcotics or systolic heart failure. The driving forces in the pathophysiology are felt to be ventilator instability associated oscillation in PaCO2 arterial partial pressure of Carbon Dioxide, continuous cositive airway pressure (CPAP related increased CO2 carbon dioxide elimination, and activation of airway and pulmonary stretch receptors triggering these central apneas. The prevalence ranges from 0.56% to 18% with no clear predictive characteristics as compared to simple obstructive sleep apnea. Prognosis is similar to obstructive sleep apnea. The central apnea component in most patients on followup using CPAP therap, has resolved. For those with continued central apneas on simple CPAP therapy, other treatment options include bilevel PAP, adaptive servoventilation, permissive flow limitation and/or drugs.

  5. Depression and poor sleep

    DEFF Research Database (Denmark)

    Sánchez, Connie; Brennum, Lise T; Stórustovu, Signe í

    2007-01-01

    The effects of five antidepressants (escitalopram, paroxetine, duloxetine, venlafaxine, and reboxetine) on the sleep architecture were investigated in freely moving rats in the light phase of a 12:12 h light:dark cycle following a single i.p. dose of antidepressant. Overall, paroxetine and escita...

  6. Sleep No More

    Institute of Scientific and Technical Information of China (English)

    陈平

    1994-01-01

    It’s the weekend, and you’re looking forward to sleeping in. But when 7 a. m. rolls around, your eyes pop open. The reason, researchers are now saying, is that you have an alarm clock in your brain.

  7. Changing your sleep habits

    Science.gov (United States)

    ... supplements, ask your health care provider about the effects they may have on your sleep. Find ways to manage stress. Learn about relaxation techniques, such as guided imagery, listening to music, or practicing yoga or meditation. Listen to your body when it ...

  8. Sleep in obese patients

    Directory of Open Access Journals (Sweden)

    Natalya Victorova Strueva

    2014-08-01

    Full Text Available Objectives: The aim of the study was to investigate the influence of duration and individual characteristics of sleep and chronotype on body weight, eating behavior, anxiety, depression, life quality, metabolic and hormonal parameters of obese patients. Materials and methods: 200 patients with primary obesity were studied: 83 men and 117 women at age from 18 to 61 years old, median age 41,5 years [31,0; 50,0]; body weight 107 kg [94; 128,5], waist circumference 112 cm [102; 124]; neck circumference 41 cm [38; 46], body mass index (BMI 36,9 [32,8; 42,3]. Results: We found an association between sleep duration, chronotype and the emotional eating. Significant sleep reduction (to less than 6 hours was associated with high level of anxiety, depression, emotional eating and insomnia. Younger age, early onset and shorter duration of obesity and brisk weight gain during last is connected to the evening chronotype. The emotional eating associated with hypersomnolence in the absence of statistically significant increase of anxiety and depression in individuals with evening chronotype. Sleep duration and chronotype have no significant effect on the body weight, metabolic, hormonal parameters and the dynamics of body. weight after 7±1 months of treatment of obesity.

  9. Gifted Students and Sleep

    Science.gov (United States)

    Harsh, John; Karnes, Frances; Eiers, Patrick

    2012-01-01

    In this article, the authors emphasize that good sleep health is essential if gifted children are to gain the greatest benefit from opportunities to grow intellectually, socially, and spiritually while maintaining good psychological and physical health. The outstanding abilities that characterize these children and enable high levels of…

  10. Aging changes in sleep

    Science.gov (United States)

    ... if any of the medicines you take may affect your sleep. If you cannot fall asleep after 20 minutes, get out of bed and do a quiet activity, such as reading or listening to music. When you feel sleepy, get back in bed ...

  11. Nap sleep spindle correlates of intelligence

    NARCIS (Netherlands)

    Ujma, P.P.; Bodizs, R.; Gombos, F.; Stintzing, J.; Konrad, B.N.; Genzel, L.; Steiger, A.; Dresler, M.

    2015-01-01

    Sleep spindles are thalamocortical oscillations in non-rapid eye movement (NREM) sleep, that play an important role in sleep-related neuroplasticity and offline information processing. Several studies with full-night sleep recordings have reported a positive association between sleep spindles and fl

  12. Can non-REM sleep be depressogenic?

    NARCIS (Netherlands)

    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 c

  13. CAN NON-REM SLEEP BE DEPRESSOGENIC

    NARCIS (Netherlands)

    BEERSMA, DGM; VANDENHOOFDAKKER, RH

    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 c

  14. To sleep or not to sleep: the ecology of sleep in artificial organisms

    Directory of Open Access Journals (Sweden)

    Nunn Charles L

    2008-05-01

    Full Text Available 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. Agents acquire food and sleep energy based on an internal circadian clock coded by 24 traits (one for each hour of the day that correspond to "genes" that evolve by means of a genetic algorithm. These traits can assume three different values that specify the agents' behavior: sleep (or search for a sleep site, eat (or search for a food site, or flexibly decide action based on relative levels of sleep energy and food energy. Individuals with higher fitness scores leave more offspring in the next generation of the simulation, and the model can therefore be used to identify evolutionarily adaptive circadian clock parameters under different ecological conditions. Results We systematically varied input parameters related to the number of food and sleep sites, the degree to which food and sleep sites overlap, and the rate at which food patches were depleted. Our results reveal that: (1 the increased costs of traveling between more spatially separated food and sleep clusters select for monophasic sleep, (2 more rapid food patch depletion reduces sleep times, and (3 agents spend more time attempting to acquire the "rarer" resource, that is, the average time spent sleeping is positively correlated with the number of food patches and negatively correlated with the number of sleep patches. "Flexible" genes, in general, do not appear to be advantageous, though their arrangements in the agents' genome show characteristic patterns that suggest that selection acts on their

  15. 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

  16. Sleep disorders in kidney disease.

    Science.gov (United States)

    De Santo, R M; Perna, A; Di Iorio, B R; Cirillo, M

    2010-03-01

    Sleep disorders are common in patients with end stage renal disease receiving hemodialysis or peritoneal dialysis. However also a well functioning renal graft does not cure the poor sleep pattern which now emerges as a problem even in early chronic kidney disease (CKD). When patients are made aware for the first time of a disease such as CKD, which may brink to dialysis or at the best to a renal transplant patients begin to experience a disordered sleep. Sleeping disorders include insomnia (I), sleep apnoea (SAS), restless legs syndrome (RLS), periodic limb movement disorder (PLMD), excessive daily sleeping (EDS), sleepwalking, nightmares, and narcolepsy. Disordered sleep did not meet the clinical and scientific interest it deserves, in addition and we do not have a well defined solution for sleeping complaints. However, awareness that a poor sleep is associated with poor quality of life and carries an increase in mortality risk has recently stimulated interest in the field. There are many putative causes for a disordered sleep in chronic kidney disease and in end-stage renal disease. For a unifying hypothesis demographic factors, lifestyles, disease related factors, psychological factors, treatment related factors, and social factor must be taken into consideration.

  17. Caffeine: sleep and daytime sleepiness.

    Science.gov (United States)

    Roehrs, Timothy; Roth, Thomas

    2008-04-01

    Caffeine is one of the most widely consumed psychoactive substances and it has profound effects on sleep and wake function. Laboratory studies have documented its sleep-disruptive effects. It clearly enhances alertness and performance in studies with explicit sleep deprivation, restriction, or circadian sleep schedule reversals. But, under conditions of habitual sleep the evidence indicates that caffeine, rather then enhancing performance, is merely restoring performance degraded by sleepiness. The sleepiness and degraded function may be due to basal sleep insufficiency, circadian sleep schedule reversals, rebound sleepiness, and/or a withdrawal syndrome after the acute, over-night, caffeine discontinuation typical of most studies. Studies have shown that caffeine dependence develops at relatively low daily doses and after short periods of regular daily use. Large sample and population-based studies indicate that regular daily dietary caffeine intake is associated with disturbed sleep and associated daytime sleepiness. Further, children and adolescents, while reporting lower daily, weight-corrected caffeine intake, similarly experience sleep disturbance and daytime sleepiness associated with their caffeine use. The risks to sleep and alertness of regular caffeine use are greatly underestimated by both the general population and physicians.

  18. Sleep can reduce proactive interference.

    Science.gov (United States)

    Abel, Magdalena; Bäuml, Karl-Heinz T

    2014-01-01

    Sleep has repeatedly been connected to processes of memory consolidation. While extensive research indeed documents beneficial effects of sleep on memory, little is yet known about the role of sleep for interference effects in episodic memory. Although two prior studies reported sleep to reduce retroactive interference, no sleep effect has previously been found for proactive interference. Here we applied a study format differing from that employed by the prior studies to induce a high degree of proactive interference, and asked participants to encode a single list or two interfering lists of paired associates via pure study cycles. Testing occurred after 12 hours of diurnal wakefulness or nocturnal sleep. Consistent with the prior work, we found sleep in comparison to wake did not affect memory for the single list, but reduced retroactive interference. In addition we found sleep reduced proactive interference, and reduced retroactive and proactive interference to the same extent. The finding is consistent with the view that arising benefits of sleep are caused by the reactivation of memory contents during sleep, which has been suggested to strengthen and stabilise memories. Such stabilisation may make memories less susceptible to competition from interfering memories at test and thus reduce interference effects.

  19. Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis

    OpenAIRE

    2006-01-01

    Objective To conduct a systematic review of the efficacy and safety of exogenous melatonin in managing secondary sleep disorders and sleep disorders accompanying sleep restriction, such as jet lag and shiftwork disorder.

  20. Long-term subjective and objective sleep analysis of total sleep time and sleep quality in real life settings.

    Science.gov (United States)

    Merilahti, Juho; Saarinen, Ari; Parkka, Juha; Antila, Kari; Mattila, Elina; Korhonen, Ilkka

    2007-01-01

    Sleep quality is one of the key elements of the human health status. By observing sleep patterns we can gain information about personal wellbeing. Consumer electronic sleep analysis solutions are now available for use in long-term conditions. In this study we compare different measures for total sleep time and sleep quality. We analyzed visually long- term sleep data collected with actigraphy, sleep logs and ambient sensors to gain more reliable results and compared these results to each single method's output. Correlations of visually analyzed total sleep time between actigraphy total sleep time (correlation coefficient (r) = 0.662, p <0.01) and sleep log total sleep time (r = 0.787, p <0.01) were high. Also comparison between subjective and objective sleep quality was analyzed and small, but significant correlation was found (r = 0.270, p < 0.01).

  1. 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.

  2. Cutaneous warming promotes sleep onset.

    Science.gov (United States)

    Raymann, Roy J E M; Swaab, Dick F; Van Someren, Eus J W

    2005-06-01

    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. This decline is mainly due to an increase in skin blood flow and consequently skin warming and heat loss. We have proposed that these intrinsically occurring changes in core and skin temperatures could modulate neuronal activity in sleep-regulating brain areas (Van Someren EJW, Chronobiol Int 17: 313-54, 2000). We here provide results compatible with this hypothesis. We obtained 144 sleep-onset latencies while directly manipulating core and skin temperatures within the comfortable range in eight healthy subjects under controlled conditions. The induction of a proximal skin temperature difference of only 0.78 +/- 0.03 degrees C (mean +/- SE) around a mean of 35.13 +/- 0.11 degrees C changed sleep-onset latency by 26%, i.e., by 3.09 minutes [95% confidence interval (CI), 1.91 to 4.28] around a mean of 11.85 min (CI, 9.74 to 14.41), with faster sleep onsets when the proximal skin was warmed. The reduction in sleep-onset latency occurred despite a small but significant decrease in subjective comfort during proximal skin warming. The induction of changes in core temperature (delta = 0.20 +/- 0.02 degrees C) and distal skin temperature (delta = 0.74 +/- 0.05 degrees C) were ineffective. Previous studies have demonstrated correlations between skin temperature and sleep-onset latency. Also, sleep disruption by ambient temperatures that activate thermoregulatory defense mechanisms has been shown. The present study is the first to experimentally demonstrate a causal contribution to sleep-onset latency of skin temperature manipulations within the normal nocturnal fluctuation range. Circadian and sleep-appetitive behavior-induced variations in skin temperature might act as an input signal to sleep-regulating systems.

  3. Sleep, sleep deprivation, autonomic nervous system and cardiovascular diseases.

    Science.gov (United States)

    Tobaldini, Eleonora; Costantino, Giorgio; Solbiati, Monica; Cogliati, Chiara; Kara, Tomas; Nobili, Lino; Montano, Nicola

    2017-03-01

    Sleep deprivation (SD) has become a relevant health problem in modern societies. We can be sleep deprived due to lifestyle habits or due to sleep disorders, such as insomnia, obstructive sleep apnea (OSA) and neurological disorders. One of the common element of sleep disorders is the condition of chronic SD, which has complex biological consequences. SD is capable of inducing different biological effects, such as neural autonomic control changes, increased oxidative stress, altered inflammatory and coagulatory responses and accelerated atherosclerosis. All these mechanisms links SD and cardiovascular and metabolic disorders. Epidemiological studies have shown that short sleep duration is associated with increased incidence of cardiovascular diseases, such as coronary artery disease, hypertension, arrhythmias, diabetes and obesity, after adjustment for socioeconomic and demographic risk factors and comorbidities. Thus, an early assessment of a condition of SD and its treatment is clinically relevant to prevent the harmful consequences of a very common condition in adult population.

  4. Sleep habits and sleep problems among Palestinian students

    Directory of Open Access Journals (Sweden)

    Zyoud Sa'ed H

    2011-07-01

    Full Text Available Abstract Aim The aim of this study was to describe sleep habits and sleep problems in a population of undergraduates in Palestine. Association between self-reported sleep quality and self-reported academic achievement was also investigated. Methods Sleep habits and problems were investigated using a convenience sample of students from An-Najah National University, Palestine. The study was carried out during spring semester, 2009. A self-administered questionnaire developed based on The Diagnostic and Statistical Manual of Mental Disorders IV criteria and Pittsburgh Sleep Quality Index was used. Results 400 students with a mean age of 20.2 ± 1.3 were studied. Reported mean duration of night sleep in the study sample was 6.4 ± 1.1 hours. The majority (58.3% of students went to bed before midnight and 18% of the total sample woke up before 6 am. Sleep latency of more than one hour was present in 19.3% of the students. Two thirds (64.8% of the students reported having at least one nocturnal awakening per night. Nightmares were the most common parasomnia reported by students. Daytime naps were common and reported in 74.5% of the study sample. Sleep quality was reported as "poor" in only 9.8% and was significantly associated with sleep latency, frequency of nocturnal awakenings, time of going to bed, nightmares but not with academic achievement. Conclusion Sleep habits among Palestinian undergraduates were comparable to those reported in European studies. Sleep problems were common and there was no significant association between sleep quality and academic achievement.

  5. Role of corticosterone on sleep homeostasis induced by REM sleep deprivation in rats.

    Science.gov (United States)

    Machado, Ricardo Borges; Tufik, Sergio; Suchecki, Deborah

    2013-01-01

    Sleep is regulated by humoral and homeostatic processes. If on one hand chronic elevation of stress hormones impair sleep, on the other hand, rapid eye movement (REM) sleep deprivation induces elevation of glucocorticoids and time of REM sleep during the recovery period. In the present study we sought to examine whether manipulations of corticosterone levels during REM sleep deprivation would alter the subsequent sleep rebound. Adult male Wistar rats were fit with electrodes for sleep monitoring and submitted to four days of REM sleep deprivation under repeated corticosterone or metyrapone (an inhibitor of corticosterone synthesis) administration. Sleep parameters were continuously recorded throughout the sleep deprivation period and during 3 days of sleep recovery. Plasma levels of adrenocorticotropic hormone and corticosterone were also evaluated. Metyrapone treatment prevented the elevation of corticosterone plasma levels induced by REM sleep deprivation, whereas corticosterone administration to REM sleep-deprived rats resulted in lower corticosterone levels than in non-sleep deprived rats. Nonetheless, both corticosterone and metyrapone administration led to several alterations on sleep homeostasis, including reductions in the amount of non-REM and REM sleep during the recovery period, although corticosterone increased delta activity (1.0-4.0 Hz) during REM sleep deprivation. Metyrapone treatment of REM sleep-deprived rats reduced the number of REM sleep episodes. In conclusion, reduction of corticosterone levels during REM sleep deprivation resulted in impairment of sleep rebound, suggesting that physiological elevation of corticosterone levels resulting from REM sleep deprivation is necessary for plentiful recovery of sleep after this stressful event.

  6. 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

  7. The Aurora Kinase in Trypanosoma brucei plays distinctive roles in metaphase-anaphase transition and cytokinetic initiation.

    Directory of Open Access Journals (Sweden)

    Ziyin Li

    2009-09-01

    Full Text Available Aurora B kinase is an essential regulator of chromosome segregation with the action well characterized in eukaryotes. It is also implicated in cytokinesis, but the detailed mechanism remains less clear, partly due to the difficulty in separating the latter from the former function in a growing cell. A chemical genetic approach with an inhibitor of the enzyme added to a synchronized cell population at different stages of the cell cycle would probably solve this problem. In the deeply branched parasitic protozoan Trypanosoma brucei, an Aurora B homolog, TbAUK1, was found to control both chromosome segregation and cytokinetic initiation by evidence from RNAi and dominant negative mutation. To clearly separate these two functions, VX-680, an inhibitor of TbAUK1, was added to a synchronized T. brucei procyclic cell population at different cell cycle stages. The unique trans-localization pattern of the chromosomal passenger complex (CPC, consisting of TbAUK1 and two novel proteins TbCPC1 and TbCPC2, was monitored during mitosis and cytokinesis by following the migration of the proteins tagged with enhanced yellow fluorescence protein in live cells with time-lapse video microscopy. Inhibition of TbAUK1 function in S-phase, prophase or metaphase invariably arrests the cells in the metaphase, suggesting an action of TbAUK1 in promoting metaphase-anaphase transition. TbAUK1 inhibition in anaphase does not affect mitotic exit, but prevents trans-localization of the CPC from the spindle midzone to the anterior tip of the new flagellum attachment zone for cytokinetic initiation. The CPC in the midzone is dispersed back to the two segregated nuclei, while cytokinesis is inhibited. In and beyond telophase, TbAUK1 inhibition has no effect on the progression of cytokinesis or the subsequent G1, S and G2 phases until a new metaphase is attained. There are thus two clearly distinct points of TbAUK1 action in T. brucei: the metaphase-anaphase transition and

  8. Are You Sleep Deprived? | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Sleep Disorders Are You Sleep Deprived? Past Issues / Summer 2015 ... ve had enough sleep? You might have a sleep disorder. There are many treatments for sleep disorders and ...

  9. [Treatment of depression with sleep deprivation and sleep phase advancement].

    Science.gov (United States)

    Riemann, D; Vollmann, J; Hohagen, F; Lohner, H; König, A; Faller, C; Edali, N; Berger, M

    1995-07-01

    Total sleep deprivation (TSD) exerts beneficial but only transient effects on mood in approximately 60% of the patients with a major depressive disorder (MDD). The positive effect of TSD is generally reversed after the next night of sleep. A pilot study of our group indicated that a consecutive one week phase advance of the sleep phase stabilized mood in more than half of the patients who responded to TSD. However, the majority of patients in our pilot study had been treated concomitantly with antidepressive medication. To exclude a possible synergistic effect of simultaneous antidepressive medication and the sleep-wake manipulation in the present study eleven medicated and sixteen drug-free depressed patients were investigated. In two thirds of the patients relapse into depression after successful TSD could be prevented. This effect seemed to be independent of adjunct antidepressant pharmacotherapy. Ten of these patients were studied polysomnographically prior to and during the treatment. Data analysis revealed that during the advance of the sleep phase no prolonged partial sleep deprivation took place. At the end of the study REM % had even increased and REM latency was still short in spite of clinical improvement, thus contradicting the assumption that REM sleep suppression is a necessary prerequisite for antidepressive therapy. The results support the hypothesis of a "critical phase" in the morning hours during which sleep can reinduce depressive mood and, vice versa, prevention of sleep during this time may act antidepressively.

  10. Sleep Problems in Asthma and COPD

    Science.gov (United States)

    ... Mini Series #5 Sleep Problems in Asthma and COPD NORMAL AIRWAY Good quality sleep is important for ... with asthma and/or Chronic Obstructive Pulmonary Disease (COPD) may have sleep issues that can lead to ...

  11. Globetrotting to a Good Night's Sleep

    Science.gov (United States)

    ... is one of the most common and troubling sleep disorders. At least 1 in 10 older adults, and ... have sleep apnea. To Find Out More MedlinePlus Sleep Disorders medlineplus.gov/sleepdisorders.html NHLBI Your Guide to ...

  12. National Center on Sleep Disorders Research

    Science.gov (United States)

    ... Resources Register for Updates The National Center on Sleep Disorders Research (NCSDR) Located within the National Heart, Lung, ... 60 percent have a chronic disorder. Each year, sleep disorders, sleep deprivation, and sleepiness add an estimated $15. ...

  13. At-a-Glance: Healthy Sleep

    Science.gov (United States)

    ... insomnia, sleep apnea, rest- less legs syndrome, or narcolepsy. Learn More More information on healthy sleep and ... Conditions Index (DCI) has fact sheets on insomnia, narcolepsy, restless legs syndrome, and sleep apnea, as well ...

  14. PHYSIOLOGICAL RESPONSES OF MEN DURING SLEEP DEPRIVATION,

    Science.gov (United States)

    The effects of 84 hours of sleep deprivation were examined in a group of six young men and compared with a group of six controls. Subjects were... sleep deprivation , physiological regulating systems are relatively unaffected by sleep loss. (Author)

  15. Infant Sleep Positioners Pose Suffocation Risk

    Science.gov (United States)

    ... For Consumers Home For Consumers Consumer Updates Infant Sleep Positioners Pose Suffocation Risk Share Tweet Linkedin Pin ... sharing options Linkedin Pin it Email Print Infant Sleep Positioner Example See more images of Infant Sleep ...

  16. Insufficient Sleep Is a Public Health Epidemic

    Science.gov (United States)

    ... this? Submit Button Past Emails CDC Features Insufficient Sleep Is a Public Health Problem Language: English Español ( ... insufficient sleep is an important public health concern. Sleep-Related Unhealthy Behaviors The Behavioral Risk Factor Surveillance ...

  17. Endothelial function and sleep: associations of flow-mediated dilation with perceived sleep quality and rapid eye movement (REM) sleep.

    Science.gov (United States)

    Cooper, Denise C; Ziegler, Michael G; Milic, Milos S; Ancoli-Israel, Sonia; Mills, Paul J; Loredo, José S; Von Känel, Roland; Dimsdale, Joel E

    2014-02-01

    Endothelial function typically precedes clinical manifestations of cardiovascular disease and provides a potential mechanism for the associations observed between cardiovascular disease and sleep quality. This study examined how subjective and objective indicators of sleep quality relate to endothelial function, as measured by brachial artery flow-mediated dilation (FMD). In a clinical research centre, 100 non-shift working adults (mean age: 36 years) completed FMD testing and the Pittsburgh Sleep Quality Index, along with a polysomnography assessment to obtain the following measures: slow wave sleep, percentage rapid eye movement (REM) sleep, REM sleep latency, total arousal index, total sleep time, wake after sleep onset, sleep efficiency and apnea-hypopnea index. Bivariate correlations and follow-up multiple regressions examined how FMD related to subjective (i.e., Pittsburgh Sleep Quality Index scores) and objective (i.e., polysomnography-derived) indicators of sleep quality. After FMD showed bivariate correlations with Pittsburgh Sleep Quality Index scores, percentage REM sleep and REM latency, further examination with separate regression models indicated that these associations remained significant after adjustments for sex, age, race, hypertension, body mass index, apnea-hypopnea index, smoking and income (Ps Quality Index increased (indicating decreased subjective sleep quality) and percentage REM sleep decreased, while REM sleep latency increased (Ps quality and adverse changes in REM sleep were associated with diminished vasodilation, which could link sleep disturbances to cardiovascular disease.

  18. Managing Sleep Disturbances in Cirrhosis

    Directory of Open Access Journals (Sweden)

    Xun Zhao

    2016-01-01

    Full Text Available Sleep disturbances, particularly daytime sleepiness and insomnia, are common problems reported by patients suffering from liver cirrhosis. Poor sleep negatively impacts patients’ quality of life and cognitive functions and increases mortality. Although sleep disturbances can be an early sign of hepatic encephalopathy (HE, many patients without HE still complain of poor quality sleep. The pathophysiology of these disturbances is not fully understood but is believed to be linked to impaired hepatic melatonin metabolism. This paper provides an overview for the clinician of common comorbidities contributing to poor sleep in patients with liver disease, mainly restless leg syndrome and obstructive sleep apnea. It discusses nondrug and pharmacologic treatment options in these patients, such as the use of light therapy and histamine (H1 blockers.

  19. Sleep stages, memory and learning.

    Science.gov (United States)

    Dotto, L

    1996-04-15

    Learning and memory can be impaired by sleep loss during specific vulnerable "windows" for several days after new tasks have been learned. Different types of tasks are differentially vulnerable to the loss of different stages of sleep. Memory required to perform cognitive procedural tasks is affected by the loss of rapid-eye-movement (REM) sleep on the first night after learning occurs and again on the third night after learning. REM-sleep deprivation on the second night after learning does not produce memory deficits. Declarative memory, which is used for the recall of specific facts, is not similarly affected by REM-sleep loss. The learning of procedural motor tasks, including those required in many sports, is impaired by the loss of stage 2 sleep, which occurs primarily in the early hours of the morning. These findings have implications for the academic and athletic performance of students and for anyone whose work involves ongoing learning and demands high standards of performance.

  20. Maternal and infant sleep postpartum.

    Science.gov (United States)

    McGuire, Elizabeth

    2013-07-01

    New parents should be aware that infants' sleep is unlike that of adults and that meeting their infant's needs is likely to disrupt their own sleep. They will need to adjust their routine to manage their own sleep needs. Parental sleep patterns in the postpartum period are tied to the infant's development of a circadian sleep-wake rhythm, and the infant's feeds. Close contact with the mother and exposure to light/dark cues appear to assist in the development of the infant's circadian rhythm. The composition of breastmilk varies over the course of 24 hours and some components produced at night are likely to contribute to the infant's day/night entrainment. There is no clear evidence that using artificial feeds improves maternal sleep. Most infants need night feeds but requirements for nighttime feeds vary with the individual.

  1. Effects of supplementing Erythrina brucei leaf as a substitute for cotton seed meal on growth performance and carcass characteristics of Sidama goats fed basal diet of natural grass hay.

    Science.gov (United States)

    Yinnesu, Asmamaw; Nurfeta, Ajebu

    2012-03-01

    The replacement value of dried Erythrina brucei leaf for cotton seed meal (CSM) on growth performance and carcass characteristics was evaluated. Twenty-five yearling buck goats (15.8 ± 1.4 kg) were assigned into five treatments in a randomized complete block design: natural grass hay alone (T1) or supplemented with 100% CSM (T2), 67% CSM + 33% E. brucei (T3), 33% CSM + 67% E. brucei (T4), and 100% E. brucei (T5) on dry matter (DM) basis. Supplemented goats consumed more (P  0.05) by the proportion of the supplements. The highest (P goats supplemented with CSM alone, whereas the lowest intake was observed in the non-supplemented group. Total CP intake decreased (P goats gained more (P goats than in the non-supplemented ones, but similar (P > 0.05) among the supplemented group. The digestibility of CP was higher (P goats, except in those goats fed E. brucei alone, than the non-supplemented group. Slaughter weight, empty body weight, hot carcass weight, dressing percentage, rib eye muscle area, and total edible offals were higher (P goats than for the non-supplemented ones. It could be concluded that E. brucei could be used as a substitute to CSM under smallholder production systems.

  2. SLEEP HABITS AMONG FIRST YEAR MEDICAL STUDENTS

    OpenAIRE

    Neera; Varun; Yogesh

    2016-01-01

    Sleep is part of the rhythm of life; without a good sleep the mind is less adaptive, mood is altered and the body loses the ability to refresh. The sleep-wake cycle of medical students is quite different and sleep deprivation, poor sleep quality, occurrence of napping episodes during the day. This study was designed to assess sleep habits in first year medical students. MATERIAL AND METHODS Participants of this study were healthy medical students of first year MBBS course of S...

  3. Inter-Hemispheric Oscillations in Human Sleep

    OpenAIRE

    Imbach, Lukas L.; Esther Werth; Ulf Kallweit; Johannes Sarnthein; Scammell, Thomas E.; Baumann, Christian R.

    2012-01-01

    Sleep is generally categorized into discrete stages based on characteristic electroencephalogram (EEG) patterns. This traditional approach represents sleep architecture in a static way, but it cannot reflect variations in sleep across time and across the cortex. To investigate these dynamic aspects of sleep, we analyzed sleep recordings in 14 healthy volunteers with a novel, frequency-based EEG analysis. This approach enabled comparison of sleep patterns with low inter-individual variability....

  4. Inter-hemispheric oscillations in human sleep

    OpenAIRE

    Imbach, L L; Werth, E; Kallweit, U; Sarnthein, J.; SCAMMELL, T. E.; Baumann, C R

    2012-01-01

    Sleep is generally categorized into discrete stages based on characteristic electroencephalogram (EEG) patterns. This traditional approach represents sleep architecture in a static way, but it cannot reflect variations in sleep across time and across the cortex. To investigate these dynamic aspects of sleep, we analyzed sleep recordings in 14 healthy volunteers with a novel, frequency-based EEG analysis. This approach enabled comparison of sleep patterns with low inter-individual variability....

  5. Polyphasic Sleep and Napping Strategies

    Science.gov (United States)

    2000-03-01

    UNCLASSIFIED Defense Technical Information Center Compilation Part Notice ADPO10471 TITLE: Polyphasic Sleep and Napping Strategies DISTRIBUTION...report. UNCLASSIFIED hfollowing comonent part numbers A cnprie the 0com ilation report- ADP010453 thru. ADP010473 20-1 Polyphasic Sleep and Napping ... Strategies Per Kristian OPSTAD Norwegian Defence Research Establishment P 0 Box 25 2027 Kjeller Norway Sleep deprivation is the most detrimental The

  6. Health Effects of Sleep Deprivation,

    Science.gov (United States)

    1990-06-01

    excretion. Excretion of vanillylmandelic acid , a major me- tabolite of NE, did not change during a total of 205 hours of sleep deprivation.102 From these...sleep, and immobility on the levels of EP, NE, metanephrine, normetanephrine, and vanillylmandelic acid under a strictly controlled diet. They found...metanephrine, normetanephrine, and vanillylmandelic acid . They observed a significant increase of normetanephrine during sleep deprivation days

  7. Sleep EEG in growth disorders.

    OpenAIRE

    Taylor, B. J.; Brook, C. G.

    1986-01-01

    The sleep of 30 children with disorders of growth and development was studied because of the known association between sleep and the secretion of hormones. Thirty three normal children were studied for comparison. The sleep of two consecutive nights was monitored at home using a small portable electroencephalogram and electro-oculogram recorder. Within the normal group there were no significant differences between sexes nor between the first and second nights of recording. There was a signifi...

  8. Sleep and Stroke

    Directory of Open Access Journals (Sweden)

    M V Padma Srivastav

    2014-03-01

    Full Text Available Circadian variations in conjunction with sleep-related heart rhythm changes and sleepdisordered breathing (SDB are contributing risk factors for stroke. Strong scientificevidence now exists indicating that SDB contributes to systemic hypertension, aprominent risk factor for stroke, and compelling circumstantial evidence is presentsuggesting that SDB raises the risk for development of stroke through other circulatorymechanisms as well. Preliminary evidence indicates that post-stroke patients have ahigher prevalence of SDB, which is likely to compromise their rehabilitation outcomes.Since SDB is modifiable with the application of CPAP and other treatment modalities,there is practical value in investigating patients at risk of stroke or post stroke forpresence of SDB. Successful application of CPAP or BiPAP therapy may improve theoutcome in both instances.Key words : Sleep, Stroke, SDB, CPAP

  9. Pentamidine for the treatment of Pneumocystis carinii pneumonia and other protozoal diseases.

    Science.gov (United States)

    Pearson, R D; Hewlett, E L

    1985-11-01

    Pentamidine isethionate, discovered to have antiprotozoal activity in 1938, has recently been approved in the United States for the treatment of Pneumocystis carinii pneumonia. Despite frequent adverse reactions, which are at times life-threatening, pentamidine remains an important alternative to trimethoprim-sulfamethoxazole for the treatment of P. carinii pneumonia in patients with a history of allergy to sulfonamides or who have severe reactions or a lack of response to treatment with trimethoprim-sulfamethoxazole. Although not approved for other indications, pentamidine has been shown to be effective when used prophylactically against Trypanosoma brucei gambiense, the cause of West African sleeping sickness, as well as for treatment of the early hemolymphatic stage of that disease, and for treatment of some forms of leishmaniasis.

  10. Sleep disorders in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Marina Romanovna Nodel'

    2011-01-01

    PD-cognition (SCOPA-Cog, and the PD quality of life scale (PDQ-39 were used. Results. Sleep fragmentation and early morning awakenings are the most common sleep disorders in PD. Pramipexole therapy resulted in a significant improvement in sleep quality, a reduction in the frequency of falling asleep and nocturnal awakenings. The improved characteristics of sleep were favored by a therapy-induced decrease in the severity of motor (hypokinesis, rigidity, tremor, nocturnal and morning dystonia and nonmotor (restless legs syndrome/acathisia, sensory disorders, nocturia PD manifestations.

  11. Steroid hormones and sleep regulation.

    Science.gov (United States)

    Terán-Pérez, G; Arana-Lechuga, Y; Esqueda-León, E; Santana-Miranda, R; Rojas-Zamorano, J Á; Velázquez Moctezuma, J

    2012-10-01

    In the search of the sleep substance, many studies have been addressed for different hormones, responsible for sleep-wake cycle regulation. In this article we mentioned the participation of steroid hormones, besides its role regulating sexual behavior, they influence importantly in the sleep process. One of the clearest relationships are that estrogen and progesterone have, that causing changes in sleep patterns associated with the hormonal cycles of women throughout life, from puberty to menopause and specific periods such as pregnancy and the menstrual cycle, including being responsible for some sleep disorders such as hypersomnia and insomnia. Another studied hormone is cortisol, a hormone released in stressful situations, when an individual must react to an extraordinary demand that threatens their survival, but also known as the hormone of awakening because the release peak occurs in the morning, although this may be altered in some sleep disorders like insomnia and mood disorders. Furthermore neurosteroids such as pregnanolone, allopregnanolone and pregnenolone are involved in the generation of slow wave sleep, the effect has been demonstrated in experimental animal studies. Thus we see that the sleep and the endocrine system saved a bidirectional relationship in which depends on each other to regulate different physiological processes including sleep.

  12. [Sleep disturbance in the elderly].

    Science.gov (United States)

    Mori, A

    1990-01-01

    Sleep structure is qualitatively and quantitatively changed by aging. The elderly usually go to bed in early evening and wake up in early morning, and they also take several naps in the day time. The polyphasic sleep is one of the typical sleep patterns found in the elderly. Comparing the sleep of the elderly with that of young adults by the method of polysomnography, the characteristics of the sleep of the elderly are in the prolongation of sleep latency, shortening of total sleep time, increase of Stage W and Stage 1, decrease of Stage 3 and 4, and also decrease of Stage REM and the advance of REM phase. Insomnia is a frequently observed symptom in the elderly. The so-called psychophysiological insomnia due to transient psychological or situational stress is common in the elderly. However, insomnia following the mental disturbance (depression), chronic use of drug or alcohol, dementia (vascular or Alzheimer type) are also important in the elderly. Sleep apnea syndrome is recently found as an important cause of insomnia. Concerning the treatment and prevention of insomnia, it is necessary to exclude the causes of insomnia, to improve the environmental conditions and to keep the regular rhythm of sleep-wake cycle. It is also important to carefully select and use the adequate hypnotics considering the pharmacokinetics and adverse effects of the drugs in the elderly.

  13. [Sleep disorders in neurological diseases].

    Science.gov (United States)

    Kotterba, S

    2015-06-01

    Sleep disorders can be diagnosed in approximately 15 % of the population and have been shown to increase with age. The relationship between sleep disorders and neurological disorders, however, is still insufficiently considered in the clinical practice. Sleep disorders can be an early symptom of the disease, such as the presence of rapid eye movement (REM) sleep behavior disorder (RBD) as an early indicator of neurodegeneration. Sleep disorders have also been shown to be a main symptom of various neurological syndromes, such as in restless legs syndrome (RLS), periodic limb movement disorder (PLMD) and narcolepsy. The international classification of sleep disorders 2nd edition (ICSD 2) describes the main diagnoses, insomnia, circadian rhythm sleep disorders, sleep-related breathing disorders and hypersomnia but all of these can also appear as symptoms in various neurological diseases. Parasomnias are largely considered a differential diagnosis to nocturnal epilepsy. In this review, the main sleep disorders are described with a particular focus on how they relate to neurological diseases; in particular, how they influence disease-related symptoms and how they affect the course of the disease.

  14. Sleeping through class to success

    DEFF Research Database (Denmark)

    Holm, Claus

    2015-01-01

    The Japanese believe in a healthy eight hours of nocturnal sleep, but they believe even more strongly that the more hours ambitious high-school students spend studying the better. This works only because they sleep less at night and a napping culture is tolerated in schools.......The Japanese believe in a healthy eight hours of nocturnal sleep, but they believe even more strongly that the more hours ambitious high-school students spend studying the better. This works only because they sleep less at night and a napping culture is tolerated in schools....

  15. Sleep loss produces false memories.

    Directory of Open Access Journals (Sweden)

    Susanne Diekelmann

    Full Text Available People sometimes claim with high confidence to remember events that in fact never happened, typically due to strong semantic associations with actually encoded events. Sleep is known to provide optimal neurobiological conditions for consolidation of memories for long-term storage, whereas sleep deprivation acutely impairs retrieval of stored memories. Here, focusing on the role of sleep-related memory processes, we tested whether false memories can be created (a as enduring memory representations due to a consolidation-associated reorganization of new memory representations during post-learning sleep and/or (b as an acute retrieval-related phenomenon induced by sleep deprivation at memory testing. According to the Deese, Roediger, McDermott (DRM false memory paradigm, subjects learned lists of semantically associated words (e.g., "night", "dark", "coal",..., lacking the strongest common associate or theme word (here: "black". Subjects either slept or stayed awake immediately after learning, and they were either sleep deprived or not at recognition testing 9, 33, or 44 hours after learning. Sleep deprivation at retrieval, but not sleep following learning, critically enhanced false memories of theme words. This effect was abolished by caffeine administration prior to retrieval, indicating that adenosinergic mechanisms can contribute to the generation of false memories associated with sleep loss.

  16. [Obstructive sleep apnea syndromes].

    Science.gov (United States)

    Poirrier, R

    1993-01-01

    Snoring and excessive sleepiness are the hallmarks of obstructive sleep apnea syndrome but other clinical manifestations are present and a precise assessment of the disease involves clear definitions of the various kinds of apnea. Several pathogenetic factors (functional, anatomical, neurological, genetical) are still being discussed. However new insights of the pathophysiology of apneas allow more reliable treatments. Central nervous and cardiovascular complications as well as the traumatic morbidity, associated with excessive daytime sleepiness, make it a major public health problem.

  17. Find a Sleep Center Near You

    Science.gov (United States)

    ... Overview Testing Process & Results CPAP Overview Benefits Side Effects Variations Tips Healthy Sleep Habits Sleep Disorders by Category Insomnias Insomnia Child Insomnia Short Sleeper Hypersomnias Narcolepsy Insufficient ...

  18. REM sleep Behaviour Disorder.

    Science.gov (United States)

    Ferini-Strambi, Luigi; Rinaldi, Fabrizio; Giora, Enrico; Marelli, Sara; Galbiati, Andrea

    2016-01-01

    Rapid Eye Movement (REM) sleep Behaviour Disorder (RBD) is a REM sleep parasomnia characterized by loss of the muscle atonia that typically occurs during REM sleep, therefore allowing patients to act out their dreams. RBD manifests itself clinically as a violent behaviour occurring during the night, and is detected at the polysomnography by phasic and/or tonic muscle activity on the electromyography channel. In absence of neurological signs or central nervous system lesions, RBD is defined as idiopathic. Nevertheless, in a large number of cases the development of neurodegenerative diseases in RBD patients has been described, with the duration of the follow-up representing a fundamental aspect. A growing number of clinical, neurophysiologic and neuropsychological studies aimed to detect early markers of neurodegenerative dysfunction in RBD patients. Anyway, the evidence of impaired cortical activity, subtle neurocognitive dysfunction, olfactory and autonomic impairment and neuroimaging brain changes in RBD patients is challenging the concept of an idiopathic form of RBD, supporting the idea of RBD as an early manifestation of a more complex neurodegenerative process.

  19. Functional characterization of two paralogs that are novel RNA binding proteins influencing mitochondrial transcripts of Trypanosoma brucei.

    Science.gov (United States)

    Kafková, Lucie; Ammerman, Michelle L; Faktorová, Drahomíra; Fisk, John C; Zimmer, Sara L; Sobotka, Roman; Read, Laurie K; Lukes, Julius; Hashimi, Hassan

    2012-10-01

    A majority of Trypanosoma brucei proteins have unknown functions, a consequence of its independent evolutionary history within the order Kinetoplastida that allowed for the emergence of several unique biological properties. Among these is RNA editing, needed for expression of mitochondrial-encoded genes. The recently discovered mitochondrial RNA binding complex 1 (MRB1) is composed of proteins with several functions in processing organellar RNA. We characterize two MRB1 subunits, referred to herein as MRB8170 and MRB4160, which are paralogs arisen from a large chromosome duplication occurring only in T. brucei. As with many other MRB1 proteins, both have no recognizable domains, motifs, or orthologs outside the order. We show that they are both novel RNA binding proteins, possibly representing a new class of these proteins. They associate with a similar subset of MRB1 subunits but not directly with each other. We generated cell lines that either individually or simultaneously target the mRNAs encoding both proteins using RNAi. Their dual silencing results in a differential effect on moderately and pan-edited RNAs, suggesting a possible functional separation of the two proteins. Cell growth persists upon RNAi silencing of each protein individually in contrast to the dual knockdown. Yet, their apparent redundancy in terms of cell viability is at odds with the finding that only one of these knockdowns results in the general degradation of pan-edited RNAs. While MRB8170 and MRB4160 share a considerable degree of conservation, our results suggest that their recent sequence divergence has led to them influencing mitochondrial mRNAs to differing degrees.

  20. Mathematical modelling of polyamine metabolism in bloodstream-form Trypanosoma brucei: an application to drug target identification.

    Directory of Open Access Journals (Sweden)

    Xu Gu

    Full Text Available We present the first computational kinetic model of polyamine metabolism in bloodstream-form Trypanosoma brucei, the causative agent of human African trypanosomiasis. We systematically extracted the polyamine pathway from the complete metabolic network while still maintaining the predictive capability of the pathway. The kinetic model is constructed on the basis of information gleaned from the experimental biology literature and defined as a set of ordinary differential equations. We applied Michaelis-Menten kinetics featuring regulatory factors to describe enzymatic activities that are well defined. Uncharacterised enzyme kinetics were approximated and justified with available physiological properties of the system. Optimisation-based dynamic simulations were performed to train the model with experimental data and inconsistent predictions prompted an iterative procedure of model refinement. Good agreement between simulation results and measured data reported in various experimental conditions shows that the model has good applicability in spite of there being gaps in the required data. With this kinetic model, the relative importance of the individual pathway enzymes was assessed. We observed that, at low-to-moderate levels of inhibition, enzymes catalysing reactions of de novo AdoMet (MAT and ornithine production (OrnPt have more efficient inhibitory effect on total trypanothione content in comparison to other enzymes in the pathway. In our model, prozyme and TSHSyn (the production catalyst of total trypanothione were also found to exhibit potent control on total trypanothione content but only when they were strongly inhibited. Different chemotherapeutic strategies against T. brucei were investigated using this model and interruption of polyamine synthesis via joint inhibition of MAT or OrnPt together with other polyamine enzymes was identified as an optimal therapeutic strategy.

  1. 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.

  2. The orthologue of Sjogren's syndrome nuclear autoantigen 1 (SSNA1 in Trypanosoma brucei is an immunogenic self-assembling molecule.

    Directory of Open Access Journals (Sweden)

    Helen P Price

    Full Text Available Primary Sjögren's Syndrome (PSS is a highly prevalent autoimmune disease, typically manifesting as lymphocytic infiltration of the exocrine glands leading to chronically impaired lacrimal and salivary secretion. Sjögren's Syndrome nuclear autoantigen 1 (SSNA1 or NA14 is a major specific target for autoantibodies in PSS but the precise function and clinical relevance of this protein are largely unknown. Orthologues of the gene are absent from many of the commonly used model organisms but are present in Chlamyodomonas reinhardtii (in which it has been termed DIP13 and most protozoa. We report the functional characterisation of the orthologue of SSNA1 in the kinetoplastid parasite, Trypanosoma brucei. Both TbDIP13 and human SSNA1 are small coiled-coil proteins which are predicted to be remote homologues of the actin-binding protein tropomyosin. We use comparative proteomic methods to identify potential interacting partners of TbDIP13. We also show evidence that TbDIP13 is able to self-assemble into fibril-like structures both in vitro and in vivo, a property which may contribute to its immunogenicity. Endogenous TbDIP13 partially co-localises with acetylated α-tubulin in the insect procyclic stage of the parasite. However, deletion of the DIP13 gene in cultured bloodstream and procyclic stages of T. brucei has little effect on parasite growth or morphology, indicating either a degree of functional redundancy or a function in an alternative stage of the parasite life cycle.

  3. 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

    Full Text Available BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.

  4. Trypanosoma brucei PUF9 regulates mRNAs for proteins involved in replicative processes over the cell cycle.

    Directory of Open Access Journals (Sweden)

    Stuart K Archer

    2009-08-01

    Full Text Available Many genes that are required at specific points in the cell cycle exhibit cell cycle-dependent expression. In the early-diverging model eukaryote and important human pathogen Trypanosoma brucei, regulation of gene expression in the cell cycle and other processes is almost entirely post-transcriptional. Here, we show that the T. brucei RNA-binding protein PUF9 stabilizes certain transcripts during S-phase. Target transcripts of PUF9--LIGKA, PNT1 and PNT2--were identified by affinity purification with TAP-tagged PUF9. RNAi against PUF9 caused an accumulation of cells in G2/M phase and unexpectedly destabilized the PUF9 target mRNAs, despite the fact that most known Puf-domain proteins promote degradation of their target mRNAs. The levels of the PUF9-regulated transcripts were cell cycle dependent, peaking in mid- to late- S-phase, and this effect was abolished when PUF9 was targeted by RNAi. The sequence UUGUACC was over-represented in the 3' UTRs of PUF9 targets; a point mutation in this motif abolished PUF9-dependent stabilization of a reporter transcript carrying the PNT1 3' UTR. LIGKA is involved in replication of the kinetoplast, and here we show that PNT1 is also kinetoplast-associated and its over-expression causes kinetoplast-related defects, while PNT2 is localized to the nucleus in G1 phase and redistributes to the mitotic spindle during mitosis. PUF9 targets may constitute a post-transcriptional regulon, encoding proteins involved in temporally coordinated replicative processes in early G2 phase.

  5. The effects of sleep deprivation and quality of sleep on cognitive performance and mental wellbeing

    OpenAIRE

    María Ósk Stefánsdóttir 1991

    2015-01-01

    Studies in the field of sleep have shown that sleep deprivation can affect mental wellbeing and furthermore that sleep is necessary for cognitive abilities. Few studies have examined the effect from both sleep duration and quality of sleep so the purpose of this study was to analyze the impact from both sleep duration and quality of sleep on mental health and cognitive performance. The present study used data from an ongoing research, monitoring cognitive workload using speech analysis. A tot...

  6. Effect of Physical Work and Sleep Loss on Recovery Sleep

    Science.gov (United States)

    1984-08-01

    Trinder, Paxton, Montgomery, Bowling and Bruck (1979), Bonnet (1980), Buguet, Roussel, Angus, Sabiston and Radomaky (1980), Browman and Cartwright (1980...483-493. Browman, C.R. and Cartwright, R.D. (1980). Exercise and sleep. Sleep Research, 9. 144. Buguet, A., Roussel, B., Angus, R., Sabiston , B. and

  7. Role of sleep endoscopy in obstructive sleep apnea syndrome

    Directory of Open Access Journals (Sweden)

    Suzan Salama

    2013-07-01

    Conclusion: Sleep endoscopy is a useful tool for the assessment of level, degree and shape of the upper airway obstruction during sleep in OSAS and this could be helpful in preoperative evaluation. Presence of obstruction at hypopharyngeal level or tongue base obstruction is an indicator of OSAS severity.

  8. Inter-hemispheric oscillations in human sleep.

    Directory of Open Access Journals (Sweden)

    Lukas L Imbach

    Full Text Available Sleep is generally categorized into discrete stages based on characteristic electroencephalogram (EEG patterns. This traditional approach represents sleep architecture in a static way, but it cannot reflect variations in sleep across time and across the cortex. To investigate these dynamic aspects of sleep, we analyzed sleep recordings in 14 healthy volunteers with a novel, frequency-based EEG analysis. This approach enabled comparison of sleep patterns with low inter-individual variability. We then implemented a new probability dependent, automatic classification of sleep states that agreed closely with conventional manual scoring during consolidated sleep. Furthermore, this analysis revealed a previously unrecognized, interhemispheric oscillation during rapid eye movement (REM sleep. This quantitative approach provides a new way of examining the dynamic aspects of sleep, shedding new light on the physiology of human sleep.

  9. Inter-hemispheric oscillations in human sleep.

    Science.gov (United States)

    Imbach, Lukas L; Werth, Esther; Kallweit, Ulf; Sarnthein, Johannes; Scammell, Thomas E; Baumann, Christian R

    2012-01-01

    Sleep is generally categorized into discrete stages based on characteristic electroencephalogram (EEG) patterns. This traditional approach represents sleep architecture in a static way, but it cannot reflect variations in sleep across time and across the cortex. To investigate these dynamic aspects of sleep, we analyzed sleep recordings in 14 healthy volunteers with a novel, frequency-based EEG analysis. This approach enabled comparison of sleep patterns with low inter-individual variability. We then implemented a new probability dependent, automatic classification of sleep states that agreed closely with conventional manual scoring during consolidated sleep. Furthermore, this analysis revealed a previously unrecognized, interhemispheric oscillation during rapid eye movement (REM) sleep. This quantitative approach provides a new way of examining the dynamic aspects of sleep, shedding new light on the physiology of human sleep.

  10. [Sleep disorders and sleep medicine in demented patients].

    Science.gov (United States)

    Mishima, Kazuo

    2012-01-01

    Demented elderly people often show severely fragmented sleep-waking patterns and are associated with disorganized circadian rhythm. Frequent nocturnal awakening and associated behavioral and psychological symptoms in demented people place a heavy burden on their families and care givers, and the development of an effective therapy is an important concern to health care practitioner and researchers. Although sleep disturbances in demented people could be classified into not only insomnia type but also irregular pattern type, differentiation has not yet been sufficiently practiced in a clinical setting. Demented people with irregular sleep pattern increase with progressive stage and are often insensitive to the usual pharmacotherapies for insomnia using benzodiazepines or antipsychotics. From the viewpoint of risk-benefit balance, chronotherapies such as artificial bright light or improvement of sleep hygiene could be useful and safety tools for sleep and behavioral problems in the demented elderly.

  11. Influence of smoking on sleep and obstructive sleep apnea syndrome.

    Science.gov (United States)

    Deleanu, Oana-Claudia; Pocora, Diana; Mihălcuţă, Stefan; Ulmeanu, Ruxandra; Zaharie, Ana-Maria; Mihălţan, Florin Dumitru

    2016-01-01

    The various ill effects that tobacco smoking has on health have been largely studied, particularly on vascular, neoplastic, and respiratory diseases. Lately, the discussion about the negative impact of cigarette smoking moved towards sleep medicine. Tobacco consumption has been associated with sleep disordered architecture, both during regular intake and after withdrawal. Its effects on sleep disordered breathing (SDB) and especially obstructive sleep apnea syndrome (OSAS) still remain a matter of debate. It is unclear whether smoking represents a risk factor for OSAS or whether smoking cessation has any beneficial effects on OSAS and its therapy. There seems to be a synergistic effect between smoking and OSAS, both causing an increase in cardiovascular morbidity. Future studies are needed in order to establish the strength of this association. We aim to review the literature regarding the consequences of smoking on sleep architecture and SDB, adding emphasis on OSAS clinical implications and treatment.

  12. Bisphosphonates inhibit the growth of Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum: a potential route to chemotherapy.

    Science.gov (United States)

    Martin, M B; Grimley, J S; Lewis, J C; Heath, H T; Bailey, B N; Kendrick, H; Yardley, V; Caldera, A; Lira, R; Urbina, J A; Moreno, S N; Docampo, R; Croft, S L; Oldfield, E

    2001-03-15

    We have investigated the effects in vitro of a series of bisphosphonates on the proliferation of Trypanosoma cruzi, Trypanosoma brucei rhodesiense, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum. The results show that nitrogen-containing bisphosphonates of the type used in bone resorption therapy have significant activity against parasites, with the aromatic species having in some cases nanomolar or low-micromolar IC(50) activity values against parasite replication (e.g. o-risedronate, IC(50) = 220 nM for T. brucei rhodesiense; risedronate, IC(50) = 490 nM for T. gondii). In T. cruzi, the nitrogen-containing bisphosphonate risedronate is shown to inhibit sterol biosynthesis at a pre-squalene level, most likely by inhibiting farnesylpyrophosphate synthase. Bisphosphonates therefore appear to have potential in treating parasitic protozoan diseases.

  13. Reduced False Memory after Sleep

    Science.gov (United States)

    Fenn, Kimberly M.; Gallo, David A.; Margoliash, Daniel; Roediger, Henry L., III; Nusbaum, Howard C.

    2009-01-01

    Several studies have shown that sleep contributes to the successful maintenance of previously encoded information. This research has focused exclusively on memory for studied events, as opposed to false memories. Here we report three experiments showing that sleep reduces false memories in the Deese-Roediger-McDermott (DRM) memory illusion. False…

  14. All about Sleep (For Parents)

    Science.gov (United States)

    ... stretches at night. At 3 months, a baby averages about 14 hours of sleep total, with 8 to 9 hours at night ( ... Months At 6 months, babies still need an average of 14 hours of sleep a day, with 2 to 3 daytime naps, ...

  15. Sleep in acute care units.

    Science.gov (United States)

    BaHammam, Ahmed

    2006-03-01

    Patients in the acute care units (ACU) are usually critically ill, making them more susceptible to the unfavorable atmosphere in the hospital. One of these unfavorable factors is sleep disruption and deprivation. Many factors may affect sleep in the ACU, including therapeutic interventions, diagnostic procedures, medications, the underlying disease process, and noise generated in the ACU environment. Many detrimental physiological effects can occur secondary to noise and sleep deprivation, including cardiovascular stimulation, increased gastric secretion, pituitary and adrenal stimulation, suppression of the immune system and wound healing, and possible contribution to delirium. Over the past few years, many studies have endeavored to objectively assess sleep in the ACUs, as well as the effect of mechanical ventilation and circadian rhythm changes critically ill patients. At this time, therefore, it is important to review published data regarding sleep in ACUs, in order to improve the knowledge and recognition of this problem by health care professionals. We have therefore reviewed the methods used to assess sleep in ACUs, factors that may affect sleep in the ACU environment, and the clinical implications of sleep disruption in the ACU.

  16. Workplace bullying and sleep difficulties

    DEFF Research Database (Denmark)

    Hansen, Åse Marie; Hogh, Annie; Garde, Anne Helene

    2014-01-01

    PURPOSE: The aims of the present study were to investigate whether being subjected to bullying and witnessing bullying at the workplace was associated with concurrent sleep difficulties, whether frequently bullied/witnesses have more sleep difficulties than occasionally bullied/witnesses, and whe......PURPOSE: The aims of the present study were to investigate whether being subjected to bullying and witnessing bullying at the workplace was associated with concurrent sleep difficulties, whether frequently bullied/witnesses have more sleep difficulties than occasionally bullied....../witnesses, and whether there were associations between being subjected to bullying or witnessing bullying at the workplace and subsequent sleep difficulties. METHODS: A total of 3,382 respondents (67 % women and 33 % men) completed a baseline questionnaire about their psychosocial work environment and health....... The overall response rate was 46 %. At follow-up 2 years later, 1671 of those responded to a second questionnaire (49 % of the 3,382 respondents at baseline). Sleep difficulties were measured in terms of disturbed sleep, awakening problems, and poor quality of sleep. RESULTS: Bullied persons and witnesses...

  17. How Sleep Activates Epileptic Networks?

    Directory of Open Access Journals (Sweden)

    Peter Halász

    2013-01-01

    Full Text Available Background. The relationship between sleep and epilepsy has been long ago studied, and several excellent reviews are available. However, recent development in sleep research, the network concept in epilepsy, and the recognition of high frequency oscillations in epilepsy and more new results may put this matter in a new light. Aim. The review address the multifold interrelationships between sleep and epilepsy networks and with networks of cognitive functions. Material and Methods. The work is a conceptual update of the available clinical data and relevant studies. Results and Conclusions. Studies exploring dynamic microstructure of sleep have found important gating mechanisms for epileptic activation. As a general rule interictal epileptic manifestations seem to be linked to the slow oscillations of sleep and especially to the reactive delta bouts characterized by A1 subtype in the CAP system. Important link between epilepsy and sleep is the interference of epileptiform discharges with the plastic functions in NREM sleep. This is the main reason of cognitive impairment in different forms of early epileptic encephalopathies affecting the brain in a special developmental window. The impairment of cognitive functions via sleep is present especially in epileptic networks involving the thalamocortical system and the hippocampocortical memory encoding system.

  18. [Relationships between sleep and addiction].

    Science.gov (United States)

    Cañellas, Francesca; de Lecea, Luis

    2012-01-01

    While it is well known that there is an interaction between sleep disorders and substance abuse, it is certainly more complex than was previously thought. There is a positive relationship both between having a substance use disorder and suffering from a sleep disorder, and vice versa. The effects on sleep depend on the substance used, but it has been shown that both during use and in withdrawal periods consumers have various sleep problems, and basically more fragmented sleep. We know that sleep problems must be taken into account to prevent addiction relapses. Recent research shows that the hypocretinergic system defined by neuropeptide hypocretin / orexin (Hcrt / ox), located in the lateral hypothalamus and involved in, among other things, the regulation of the sleep-wake cycle, may play an important role in addictive behaviors. Different studies have demonstrated interactions between the hypocretinergic system, acute response to stress circuits and reward systems. We also know that selective optogenetic activation of the hypocretinergic system increases the probability of transition from sleep to wakefulness, and is sufficient for initiating an addictive compulsive behavior relapse. Hypocretinergic system activation could explain the hyperarousal associated with stress and addiction. Improved knowledge of this interaction would help us to understand better the mechanisms of addiction and find new strategies for the treatment of addictions.

  19. Sleep and Performance Research Center

    Science.gov (United States)

    2012-05-01

    Jiang P, Striz M, Wisor JP and O’Hara BF (2011) Behavioral and genetic dissection of a mouse model for advanced sleep phase syndrome, Sleep 34:39-48... Chronobiology Society, Melbourne, Australia, 2011: 11–16. Romeo, R.D. and Karatsoreos, I.N. (2011) “Adolescence and Stress: From HPA function to Brain

  20. Sleep-patterns, co-sleeping and parent's perception of sleep among school children: Comparison of domicile and gender

    Directory of Open Access Journals (Sweden)

    Ravi Gupta

    2016-07-01

    Conclusion: Television watching before bedtime was more common among urban school children and they had shorter total sleep time. They had signs of sleep deprivation. Room sharing was more common among rural children. Despite longer sleep time, parents of rural children felt the need for more sleep.

  1. Effect of experimental single Ancylostoma caninum and mixed infections of Trypanosoma brucei and Trypanosoma congolense on the humoural immune response to anti-rabies vaccination in dogs

    Institute of Scientific and Technical Information of China (English)

    Nwoha Rosemary Ijeoma Ogechi; Anene Boniface Maduka

    2015-01-01

    Objective:To determine the effect of Ancylostoma caninum (A. caninum) and trypanosome parasites on the immune response to vaccination in dogs in endemic environments. Methods:Sixteen dogs for the experiment were grouped into 4 of 4 members each. Group I was the uninfected control one, and GPII was infected with A. caninum; GPIII was infected with A. caninum/Trypanosoma congolense (T. congolense), and GPIV was infected with Trypanosoma brucei (T. brucei)/A. caninum. The dogs were first vaccinated with antirabies vaccine before infecting GPII, GPIII and GPIV with A. caninum which were done 4 weeks after vaccination. By 2-week post-vaccination, trypanosome parasites were superimposed on both GPIII and GPIV. A secondary vaccination was given to GPI, GPII, GPIII, and GPIV by Week 12 of the experiment (4 weeks post treatment). Results:The prepatent period was (3.00 ± 1.40) days, in the conjunct infection of T. brucei/A. caninum. It was (9.00 ± 1.10) days, in conjunct T. congolense/A. caninum. The prepatent period of A. caninum was (14.0 ± 2.0) days in the single A. caninum group and (13.0 ± 1.0) days in the conjunct trypanosome/A. caninum. At the 1st week after vaccination, the antibody titer in all the vaccinated groups (GPI, GPII, GPIII, and GPIV) significantly increased (P Conclusions:It was therefore concluded that A. caninum, T. brucei and T. congolense induced immunosuppression in antirabies vaccination in dogs.

  2. Sleep in intensive care unit

    DEFF Research Database (Denmark)

    Boyko, Yuliya; Jennum, Poul; Nikolic, Miki

    2017-01-01

    PURPOSE: To determine if improving intensive care unit (ICU) environment would enhance sleep quality, assessed by polysomnography (PSG), in critically ill mechanically ventilated patients. MATERIALS AND METHODS: Randomized controlled trial, crossover design. The night intervention "quiet routine......" protocol was directed toward improving ICU environment between 10pm and 6am. Noise levels during control and intervention nights were recorded. Patients on mechanical ventilation and able to give consent were eligible for the study. We monitored sleep by PSG.The standard (American Association of Sleep...... Medicine) sleep scoring criteria were insufficient for the assessment of polysomnograms. Modified classification for sleep scoring in critically ill patients, suggested by Watson et al. (Crit Care Med 2013;41:1958-1967), was used. RESULTS: Sound level analysis showed insignificant effect...

  3. Inuit interpretations of sleep paralysis.

    Science.gov (United States)

    Law, Samuel; Kirmayer, Laurence J

    2005-03-01

    Traditional and contemporary Inuit concepts of sleep paralysis were investigated through interviews with elders and young people in Iqaluit, Baffin Island. Sleep paralysis was readily recognized by most respondents and termed uqumangirniq (in the Baffin region) or aqtuqsinniq (Kivalliq region). Traditional interpretations of uqumangirniq referred to a shamanistic cosmology in which the individual's soul was vulnerable during sleep and dreaming. Sleep paralysis could result from attack by shamans or malevolent spirits. Understanding the experience as a manifestation of supernatural power, beyond one's control, served to reinforce the experiential reality and presence of the spirit world. For contemporary youth, sleep paralysis was interpreted in terms of multiple frameworks that incorporated personal, medical, mystical, traditional/shamanistic, and Christian views, reflecting the dynamic social changes taking place in this region.

  4. Adopted youth and sleep difficulties

    Directory of Open Access Journals (Sweden)

    Radcliff Z

    2016-12-01

    Full Text Available Zach Radcliff, Allison Baylor, Bruce Rybarczyk Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA Abstract: Sleep is a critical component of healthy development for youth, with cascading effects on youth’s biological growth, psychological well-being, and overall functioning. Increased sleep difficulties are one of many disruptions that adopted youth may face throughout the adoption process. Sleep difficulties have been frequently cited as a major concern by adoptive parents and hypothesized in the literature as a problem that may affect multiple areas of development and functioning in adopted youth. However, there is limited research exploring this relationship. Using a biopsychosocial framework, this paper reviews the extant literature to explore the development, maintenance, and impact of sleep difficulties in adopted youth. Finally, implications for future research and clinical interventions are outlined. Keywords: adoption, sleep, youth

  5. Sleep in Children and Adolescents with Angelman Syndrome: Association with Parent Sleep and Stress

    Science.gov (United States)

    Goldman, S. E.; Bichell, T. J.; Surdyka, K.; Malow, B. A.

    2012-01-01

    Background: Sleep concerns are common in children with Angelman syndrome, with 20-80% of individuals having a decreased sleep need and/or abnormal sleep-wake cycles. The impact of these sleep behaviours on parental sleep and stress is not known. Method: Through the use of standardised questionnaires, wrist actigraphy and polysomnography, we…

  6. About sleep's role in memory.

    Science.gov (United States)

    Rasch, Björn; Born, Jan

    2013-04-01

    Over more than a century of research has established the fact that sleep benefits the retention of memory. In this review we aim to comprehensively cover the field of "sleep and memory" research by providing a historical perspective on concepts and a discussion of more recent key findings. Whereas initial theories posed a passive role for sleep enhancing memories by protecting them from interfering stimuli, current theories highlight an active role for sleep in which memories undergo a process of system consolidation during sleep. Whereas older research concentrated on the role of rapid-eye-movement (REM) sleep, recent work has revealed the importance of slow-wave sleep (SWS) for memory consolidation and also enlightened some of the underlying electrophysiological, neurochemical, and genetic mechanisms, as well as developmental aspects in these processes. Specifically, newer findings characterize sleep as a brain state optimizing memory consolidation, in opposition to the waking brain being optimized for encoding of memories. Consolidation originates from reactivation of recently encoded neuronal memory representations, which occur during SWS and transform respective representations for integration into long-term memory. Ensuing REM sleep may stabilize transformed memories. While elaborated with respect to hippocampus-dependent memories, the concept of an active redistribution of memory representations from networks serving as temporary store into long-term stores might hold also for non-hippocampus-dependent memory, and even for nonneuronal, i.e., immunological memories, giving rise to the idea that the offline consolidation of memory during sleep represents a principle of long-term memory formation established in quite different physiological systems.

  7. Subjective sleep efficiency of hemodialysis patients

    NARCIS (Netherlands)

    B.C.P. Koch; J.E. Nagtegaal; E.C. Hagen; W.Th. van Dorp; J.B.S. Boringa; G.A. Kerkhof; P.M. ter Wee

    2008-01-01

    Background: Sleep disturbances have a major influence on quality of life. A commonly used measure of sleep disturbances is sleep efficiency. The purpose of this study was to investigate the prevalence of decreased subjective sleep efficiency in hemodialysis patients. An additional goal was to identi

  8. Sleep in Children with Asperger Syndrome

    Science.gov (United States)

    Paavonen, E. Juulia; Vehkalahti; Kimmo; Vanhala, Raija; von Wendt, Lennart; Nieminen-von Wendt, Taina; Aronen, Eeva T.

    2008-01-01

    The prevalence of sleep disturbances in 52 children with Asperger syndrome (AS) as compared with 61 healthy controls (all subjects aged 5-17 years) was investigated. Problems with sleep onset and maintenance, sleep-related fears, negative attitudes toward sleeping, and daytime somnolence were more frequent among children with AS than among…

  9. Sleep Disorders in Patients with Bronchial Asthma

    OpenAIRE

    Cukic, Vesna; Lovre, Vladimir; Dragisic, Dejan

    2011-01-01

    Respiratory disturbances during sleep are recognized as extremely common disorders with important clinical consequences. Breathing disorders during sleep can result in broad range of clinical manifestations, the most prevalent of which are unrefreshing sleep, daytime sleepiness and fatigue, and cognitive impairmant. There is also evidence that respiratory-related sleep disturbances can contribute to several common cardiovascular and metabolic disorders, including systemic hypertension, cardia...

  10. Normal sleep and its neurophysiological regulation

    NARCIS (Netherlands)

    W.F. Hofman; L.M. Talamini

    2015-01-01

    Normal sleep consists of two states: NREM (light and deep sleep) and REM, alternating in a cyclical pattern. The sleep/wake rhythm is regulated by two processes: the sleep propensity, building up during wake, and the circadian rhythm, imposed by the suprachiasmatic nucleus. The arousal pathways in t

  11. Dyspnoea waking from sleep

    Directory of Open Access Journals (Sweden)

    A.O. Yildirim*

    2013-12-01

    Discussion: OSAS, as drivers working people, especially at night, is a disease that leads to serious consequences. Polysomnography is the gold standard for diagnosis and severity of the syndrome, apnoea-hypopnea index (AHI is determined by; AHI = normal  30 is severe. From repetitive episodes of apnoea increased sympathetic nerve activity, oxidative stress, intrathoracic pressure swings, sudden jumps in systemic blood pressure, hypoxia and hypercapnia. Emergency services waking from sleep dyspnoea, lethargy and fatigue in patients admitted with complaints of snoring and OSAS cannot be forgotten.

  12. Sleep disorders in Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Israt Jahan

    2009-10-01

    Full Text Available Israt Jahan1, Robert A Hauser2, Kelly L Sullivan1, Amber Miller1, Theresa A Zesiewicz11Department of Neurology, Parkinson’s Research Foundation, 2Departments of Neurology, Molecular Pharmacology, and Physiology, University of South Florida, Parkinson’s Disease and Movement Disorders Center, Tampa, FL, USAAbstract: 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. Keywords: insomnia, restless legs syndrome, sleep apnea

  13. Interventions for Sleep Disturbance in Bipolar Disorder.

    Science.gov (United States)

    Harvey, Allison G; Kaplan, Katherine A; Soehner, Adriane M

    2015-03-01

    Bipolar disorder is a severe and chronic disorder, ranked in the top 10 leading causes of disability worldwide. Sleep disturbances are strongly coupled with interepisode dysfunction and symptom worsening in bipolar disorder. Experimental studies suggest that sleep deprivation can trigger manic relapse. There is evidence that sleep deprivation can have an adverse impact on emotion regulation the following day. The clinical management of the sleep disturbances experienced by bipolar patients, including insomnia, hypersomnia delayed sleep phase, and irregular sleep-wake schedule, may include medication approaches, psychological interventions, light therapies and sleep deprivation.

  14. Sleep spindles predict stress-related increases in sleep disturbances

    Directory of Open Access Journals (Sweden)

    Thien Thanh eDang-Vu

    2015-02-01

    Full Text Available Background and Aim: Predisposing factors place certain individuals at higher risk for insomnia, especially in the presence of precipitating conditions such as stressful life events. Sleep spindles have been shown to play an important role in the preservation of sleep continuity. Lower spindle density might thus constitute an objective predisposing factor for sleep reactivity to stress. The aim of this study was therefore to evaluate the relationship between baseline sleep spindle density and the prospective change in insomnia symptoms in response to a standardized academic stressor. Methods: 12 healthy students had a polysomnography (PSG recording during a period of lower stress at the beginning of the academic semester, along with an assessment of insomnia complaints using the Insomnia Severity Index (ISI. They completed a second ISI assessment at the end of the semester, a period coinciding with the week prior to final examinations and thus higher stress. Spindle density, amplitude, duration and frequency, as well as sigma power were computed from C4-O2 electroencephalography (EEG derivation during stages N2-N3 of non-rapid-eye-movement (NREM sleep, across the whole night and for each NREM sleep period. To test for the relationship between spindle density and changes in insomnia symptoms in response to academic stress, spindle measurements at baseline were correlated with changes in ISI across the academic semester.Results: Spindle density (as well as spindle amplitude and sigma power, particularly during the first NREM sleep period, negatively correlated with changes in ISI (p < 0.05. Conclusion: Lower spindle activity, especially at the beginning of the night, prospectively predicted larger increases in insomnia symptoms in response to stress. This result indicates that individual differences in sleep spindle activity contribute to the differential vulnerability to sleep disturbances in the face of precipitating factors.

  15. Update of sleep alterations in depression

    Directory of Open Access Journals (Sweden)

    Andrés Barrera Medina

    2014-09-01

    Full Text Available Sleep disturbances in depression are up to 70%. Patients frequently have difficulty in falling asleep, frequent awakenings during the night and non-restorative sleep. Sleep abnormalities in depression are mainly characterized by increased rapid eye movement (REM sleep and reduced slow wave sleep. Among the mechanisms of sleep disturbances in depression are hyperactivation of the hypothalamic-pituitary-adrenal axis, CLOCK gene polymorphism and primary sleep disorders. The habenula is a structure regulating the activities of monoaminergic neurons in the brain. The hyperactivation of the habenula has also been implicated, together with sleep disturbances, in depression. The presence of depression in primary sleep disorders is common. Sleep disturbances treatment include pharmacotherapy or Cognitive Behavioral Therapy.

  16. Update of sleep alterations in depression.

    Science.gov (United States)

    Medina, Andrés Barrera; Lechuga, DeboraYoaly Arana; Escandón, Oscar Sánchez; Moctezuma, Javier Velázquez

    2014-09-01

    Sleep disturbances in depression are up to 70%. Patients frequently have difficulty in falling asleep, frequent awakenings during the night and non-restorative sleep. Sleep abnormalities in depression are mainly characterized by increased rapid eye movement (REM) sleep and reduced slow wave sleep. Among the mechanisms of sleep disturbances in depression are hyperactivation of the hypothalamic-pituitary-adrenal axis, CLOCK gene polymorphism and primary sleep disorders. The habenula is a structure regulating the activities of monoaminergic neurons in the brain. The hyperactivation of the habenula has also been implicated, together with sleep disturbances, in depression. The presence of depression in primary sleep disorders is common. Sleep disturbances treatment include pharmacotherapy or Cognitive Behavioral Therapy.

  17. Associations of sleep disturbance with ADHD

    DEFF Research Database (Denmark)

    Hvolby, A.

    2015-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is commonly associated with disordered or disturbed sleep. The relationships of ADHD with sleep problems, psychiatric comorbidities and medications are complex and multidirectional. Evidence from published studies comparing sleep in individuals...... with ADHD with typically developing controls is most concordant for associations of ADHD with: hypopnea/apnea and peripheral limb movements in sleep or nocturnal motricity in polysomnographic studies; increased sleep onset latency and shorter sleep time in actigraphic studies; and bedtime resistance......, difficulty with morning awakenings, sleep onset difficulties, sleep-disordered breathing, night awakenings and daytime sleepiness in subjective studies. ADHD is also frequently coincident with sleep disorders (obstructive sleep apnea, peripheral limb movement disorder, restless legs syndrome and circadian...

  18. Sleep Disorders in Patients with Bronchial Asthma

    Science.gov (United States)

    Cukic, Vesna; Lovre, Vladimir; Dragisic, Dejan

    2011-01-01

    Respiratory disturbances during sleep are recognized as extremely common disorders with important clinical consequences. Breathing disorders during sleep can result in broad range of clinical manifestations, the most prevalent of which are unrefreshing sleep, daytime sleepiness and fatigue, and cognitive impairmant. There is also evidence that respiratory-related sleep disturbances can contribute to several common cardiovascular and metabolic disorders, including systemic hypertension, cardiac dysfunction, and insulin-resistance. Correlations are found between asthma-related symptoms and sleep disturbances. Difficulties inducing sleep, sleep fragmentation on polysomnography, early morning awakenings and daytime sleepiness are more common in asthmatics compared with subjects without asthma. The “morning deep” in asthma is relevant for the characterization of asthma severity, and impact drugs’ choices. Sleep and night control of asthma could be relevant to evaluate disease’s control. Appropriate asthma control recovering is guarantor for better sleep quality in these patients and less clinical consequences of respiratory disturbances during sleep. PMID:23678304

  19. The role of sleep in migraine attacks

    Directory of Open Access Journals (Sweden)

    Elaine Inamorato

    1993-11-01

    Full Text Available Migraine attacks may be precipitated by sleep deprivation or excessive sleep and sleep is also associated with relief of migraine attacks. In view of this variable relationship we studied the records of 159 consecutive outpatients of our Headache Unit. In 121 records there was reference to sleep involvement, in 55% by a single form and in 45% by more than one form. When only one form was related, relief was most common (70%. 30% of that group of patients had the migraine attack precipitated by sleep, 24% by deprivation and 6% by sleep excess. When the effects of sleep were multiple, these effects were as expected logically in 65%: «in accordance» group (e.g attack precipitated by sleep deprivation and relieved by sleep onset. In a second group, («conflicting» where the involvement was not logical, there were three different combinations of sleep involvement, possibly due to more than one pathophysiological mechanism.

  20. Sleep Endoscopy in the Evaluation of Pediatric Obstructive Sleep Apnea

    Directory of Open Access Journals (Sweden)

    Aaron C. Lin

    2012-01-01

    Full Text Available Pediatric obstructive sleep apnea (OSA is not always resolved or improved with adenotonsillectomy. Persistent or complex cases of pediatric OSA may be due to sites of obstruction in the airway other than the tonsils and adenoids. Identifying these areas in the past has been problematic, and therefore, therapy for OSA in children who have failed adenotonsillectomy has often been unsatisfactory. Sleep endoscopy is a technique that can enable the surgeon to determine the level of obstruction in a sleeping child with OSA. With this knowledge, site-specific surgical therapy for persistent and complex pediatric OSA may be possible.