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Sample records for brucei gambiense sleeping

  1. Mechanism of Trypanosoma brucei gambiense resistance to human serum

    DEFF Research Database (Denmark)

    Uzureau, Pierrick; Uzureau, Sophie; Lecordier, Laurence;

    2013-01-01

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

  2. The TgsGP gene is essential for resistance to human serum in Trypanosoma brucei gambiense.

    Science.gov (United States)

    Capewell, Paul; Clucas, Caroline; DeJesus, Eric; Kieft, Rudo; Hajduk, Stephen; Veitch, Nicola; Steketee, Pieter C; Cooper, Anneli; Weir, William; MacLeod, Annette

    2013-01-01

    Trypanosoma brucei gambiense causes 97% of all cases of African sleeping sickness, a fatal disease of sub-Saharan Africa. Most species of trypanosome, such as T. b. brucei, are unable to infect humans due to the trypanolytic serum protein apolipoprotein-L1 (APOL1) delivered via two trypanosome lytic factors (TLF-1 and TLF-2). Understanding how T. b. gambiense overcomes these factors and infects humans is of major importance in the fight against this disease. Previous work indicated that a failure to take up TLF-1 in T. b. gambiense contributes to resistance to TLF-1, although another mechanism is required to overcome TLF-2. Here, we have examined a T. b. gambiense specific gene, TgsGP, which had previously been suggested, but not shown, to be involved in serum resistance. We show that TgsGP is essential for resistance to lysis as deletion of TgsGP in T. b. gambiense renders the parasites sensitive to human serum and recombinant APOL1. Deletion of TgsGP in T. b. gambiense modified to uptake TLF-1 showed sensitivity to TLF-1, APOL1 and human serum. Reintroducing TgsGP into knockout parasite lines restored resistance. We conclude that TgsGP is essential for human serum resistance in T. b. gambiense. PMID:24098129

  3. The TgsGP gene is essential for resistance to human serum in Trypanosoma brucei gambiense.

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    Paul Capewell

    Full Text Available Trypanosoma brucei gambiense causes 97% of all cases of African sleeping sickness, a fatal disease of sub-Saharan Africa. Most species of trypanosome, such as T. b. brucei, are unable to infect humans due to the trypanolytic serum protein apolipoprotein-L1 (APOL1 delivered via two trypanosome lytic factors (TLF-1 and TLF-2. Understanding how T. b. gambiense overcomes these factors and infects humans is of major importance in the fight against this disease. Previous work indicated that a failure to take up TLF-1 in T. b. gambiense contributes to resistance to TLF-1, although another mechanism is required to overcome TLF-2. Here, we have examined a T. b. gambiense specific gene, TgsGP, which had previously been suggested, but not shown, to be involved in serum resistance. We show that TgsGP is essential for resistance to lysis as deletion of TgsGP in T. b. gambiense renders the parasites sensitive to human serum and recombinant APOL1. Deletion of TgsGP in T. b. gambiense modified to uptake TLF-1 showed sensitivity to TLF-1, APOL1 and human serum. Reintroducing TgsGP into knockout parasite lines restored resistance. We conclude that TgsGP is essential for human serum resistance in T. b. gambiense.

  4. Mechanism of Trypanosoma brucei gambiense (group 1) resistance to human trypanosome lytic factor.

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    Kieft, Rudo; Capewell, Paul; Turner, C Michael R; Veitch, Nicola J; MacLeod, Annette; Hajduk, Stephen

    2010-09-14

    Human innate immunity against most African trypanosomes, including Trypanosoma brucei brucei, is mediated by a minor subclass of toxic serum HDL, called trypanosome lytic factor-1 (TLF-1). This HDL contains two primate specific proteins, apolipoprotein L-1 and haptoglobin (Hp)-related protein, as well as apolipoprotein A-1. These assembled proteins provide a powerful defense against trypanosome infection. Trypanosoma brucei rhodesiense causes human African sleeping sickness because it has evolved an inhibitor of TLF-1, serum resistance-associated (SRA) protein. Trypanosoma brucei gambiense lacks the SRA gene, yet it infects humans. As transfection of T. b. gambiense (group 1) is not possible, we initially used in vitro-selected TLF-1-resistant T. b. brucei to examine SRA-independent mechanisms of TLF-1 resistance. Here we show that TLF-1 resistance in T. b. brucei is caused by reduced expression of the Hp/Hb receptor gene (TbbHpHbR). Importantly, T. b. gambiense (group 1) also showed a marked reduction in uptake of TLF-1 and a corresponding decrease in expression of T. b. gambiense Hp/Hb receptor (TbgHpHbR). Ectopic expression of TbbHpHbR in TLF-1-resistant T. b. brucei rescued TLF-1 uptake, demonstrating that decreased TbbHpHbR expression conferred TLF-1 resistance. Ectopic expression of TbgHpHbR in TLF-1-resistant T. b. brucei failed to rescue TLF-1 killing, suggesting that coding sequence changes altered Hp/Hb receptor binding affinity for TLF-1. We propose that the combination of coding sequence mutations and decreased expression of TbgHpHbR directly contribute to parasite evasion of human innate immunity and infectivity of group 1 T. b. gambiense. PMID:20805508

  5. Latent Trypanosoma brucei gambiense foci in Uganda: a silent epidemic in children and adults?

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    Wastling, S L; Picozzi, K; Wamboga, C; VON Wissmann, B; Amongi-Accup, C; Wardrop, N A; Stothard, J R; Kakembo, A; Welburn, S C

    2011-10-01

    Trypanosoma brucei gambiense sleeping sickness follows a long asymptomatic phase and persists in ancient foci from which epidemic clinical disease arises. A putative focus of T. b. gambiense infections has been identified, initially in mothers and young children, on the Lake Albert shoreline of Western Uganda leading to mass screening of 6207 individuals in September 2008. T. b. gambiense infections were identified by Card Agglutination Test for Trypanosomiasis (CATT) and sub-species-specific PCR although parasitological methods failed to confirm any patent trypanosome infections. In April 2009, CATT positives were re-visited; diagnosis of individuals by CATT and PCR was unstable over the two time points and parasites remained undetected, even using mini Anion Exchange Centrifugation Technique (mAECT). These observations suggest the possibility of a silent focus of disease, where all infected individuals are in a latent stage, and highlight our limited understanding of the local natural history and disease progression of T. b. gambiense in children and adults. PMID:21554841

  6. 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.

  7. Estimates of the duration of the early and late stage of gambiense sleeping sickness

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    Chandramohan Daniel; Haydon Daniel T; Filipe João AN; Checchi Francesco; Chappuis François

    2008-01-01

    Abstract Background The durations of untreated stage 1 (early stage, haemo-lymphatic) and stage 2 (late stage, meningo-encephalitic) human African trypanosomiasis (sleeping sickness) due to Trypanosoma brucei gambiense are poorly quantified, but key to predicting the impact of screening on transmission. Here, we outline a method to estimate these parameters. Methods We first model the duration of stage 1 through survival analysis of untreated serological suspects detected during Médecins Sans...

  8. Wild fauna as a probable animal reservoir for Trypanosoma brucei gambiense in Cameroon

    OpenAIRE

    Njiokou, F.; Laveissière, Claude; Simo, G.; Nkinin, S.; Grébaut, Pascal; Cuny, Gérard; Herder, Stéphane

    2006-01-01

    In order to Study the existence of a wild animal reservoir for Trypanosoma brucei gambiense in South Cameroon, blood was collected from wild animals in three human African trypanosomiasis foci and from a nonendemic control area. The 1142 wild animals sampled belonged to 36 different species pertaining to eight orders (407 primates, 347 artiodactyls, 265 rodents, 54 pangolins, 53 carnivores, 11 Saurians and crocodilians, and five hyraxes). QBC (R) and KIVI tests detected trypanosomes on 1.7% (...

  9. Screening of Trypanosoma brucei gambiense in Domestic Livestock and Tsetse Flies from an Insular Endemic Focus (Luba, Equatorial Guinea)

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    Cordon-Obras, Carlos; García-Estébanez, Carmen; Ndong-Mabale, Nicolás; Abaga, Simón; Ndongo-Asumu, Pedro; Benito, Agustín; Cano, Jorge

    2010-01-01

    Background Sleeping sickness is spread over 36 Sub-Saharan African countries. In West and Central Africa, the disease is caused by Trypanosoma brucei gambiense, which produces a chronic clinical manifestation. The Luba focus (Bioko Island, Equatorial Guinea) has not reported autochthonous sleeping sickness cases since 1995, but given the complexity of the epidemiological cycle, the elimination of the parasite in the environment is difficult to categorically ensure. Methodology/Principal Findings The aim of this work is to assess, by a molecular approach (Polymerase Chain Reaction, PCR), the possible permanence of T. b. gambiense in the vector (Glossina spp.) and domestic fauna in order to improve our understanding of the epidemiological situation of the disease in an isolated focus considered to be under control. The results obtained show the absence of the parasite in peridomestic livestock but its presence, although at very low rate, in the vector. On the other hand, interesting entomological data highlight that an elevated concentration of tsetse flies was observed in two out of the ten villages considered to be in the focus. Conclusions These findings demonstrate that even in conditions of apparent control, a complete parasite clearance is difficult to achieve. Further investigations must be focused on animal reservoirs which could allow the parasites to persist without leading to human cases. In Luba, where domestic livestock are scarcer than other foci in mainland Equatorial Guinea, the epidemiological significance of wild fauna should be assessed to establish their role in the maintenance of the infection. PMID:20544031

  10. 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.

  11. Molecular evidence of a Trypanosoma brucei gambiense sylvatic cycle in the human african trypanosomiasis foci of Equatorial Guinea.

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    Cordon-Obras, Carlos; Rodriguez, Yasmin Fermin; Fernandez-Martinez, Amalia; Cano, Jorge; Ndong-Mabale, Nicolas; Ncogo-Ada, Policarpo; Ndongo-Asumu, Pedro; Aparicio, Pilar; Navarro, Miguel; Benito, Agustin; Bart, Jean-Mathieu

    2015-01-01

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

  12. Molecular evidence of a Trypanosoma brucei gambiense sylvatic cycle in the human african trypanosomiasis foci of Equatorial Guinea

    Science.gov (United States)

    Cordon-Obras, Carlos; Rodriguez, Yasmin Fermin; Fernandez-Martinez, Amalia; Cano, Jorge; Ndong-Mabale, Nicolas; Ncogo-Ada, Policarpo; Ndongo-Asumu, Pedro; Aparicio, Pilar; Navarro, Miguel; Benito, Agustin; Bart, Jean-Mathieu

    2015-01-01

    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. PMID:26257727

  13. 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.

  14. Trypanosoma brucei gambiense Adaptation to Different Mammalian Sera Is Associated with VSG Expression Site Plasticity

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    Cordon-Obras, Carlos; Cano, Jorge; González-Pacanowska, Dolores; Benito, Agustin; Navarro, Miguel; Bart, Jean-Mathieu

    2013-01-01

    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 supporting

  15. 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 knowledge essential for Cerrado conservation and sustainable development. PMID:26222897

  16. 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.

  17. 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.

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

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    Biteau, Nicolas; Asencio, Corinne; Izotte, Julien; Rousseau, Benoit; Fèvre, Muriel; Pillay, Davita; Baltz, Théo

    2016-01-01

    Trypanosoma brucei gambiense, transmitted by the tsetse fly, is the main causative agent of Human African trypanosomosis in West Africa and poses a significant health risk to 70 million people. Disease progression varies depending on host immunity, but usually begins with a haemo-lymphatic phase, followed by parasite invasion of the central nervous system. In the current study, the tropism of T. b. gambiense 1135, causing a low level chronic 'silent' infection, was monitored in a murine model using bioluminescence imaging and PCR. A tropism to the reproductive organs, in addition to the central nervous system, after 12-18 months of infection was observed. Bioluminescent analysis of healthy females crossed with infected males showed that 50%, 62.5% and 37.5% of the female mice were subsequently positive for parasites in their ovaries, uteri and brain respectively. Although PCR confirmed the presence of parasites in the uterus of one of these mice, the blood of all mice was negative by PCR and LAMP. Subsequently, bioluminescent imaging of the offspring of infected female mice crossed with healthy males indicated parasites were present in the reproductive organs of both male (80%) and female (60%) offspring. These findings imply that transmission of T. b. gambiense 1135 occurs horizontally, most probably via sexual contact, and vertically in a murine model, which raises the possibility of a similar transmission in humans. This has wide reaching implications. Firstly, the observations made in this study are likely to be valid for wild animals acting as a reservoir for T. b. gambiense. Also, the reproductive organs may act as a refuge for parasites during drug treatment in a similar manner to the central nervous system. This could leave patients at risk of a relapse, ultimately allowing them to act as a reservoir for subsequent transmission by tsetse and possibly, horizontally and vertically. PMID:26735855

  19. 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.

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

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    DeJesus, E; Kieft, R; Albright, B; Stephens, N A; Hajduk, S L

    2013-01-01

    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. PMID:23637606

  1. Genotypic status of the TbAT1/P2 adenosine transporter of Trypanosoma brucei gambiense isolates from Northwestern Uganda following melarsoprol withdrawal.

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    Anne J N Kazibwe

    Full Text Available BACKGROUND: The development of arsenical and diamidine resistance in Trypanosoma brucei is associated with loss of drug uptake by the P2 purine transporter as a result of alterations in the corresponding T. brucei adenosine transporter 1 gene (TbAT1. Previously, specific TbAT1 mutant type alleles linked to melarsoprol treatment failure were significantly more prevalent in T. b. gambiense from relapse patients at Omugo health centre in Arua district. Relapse rates of up to 30% prompted a shift from melarsoprol to eflornithine (alpha-difluoromethylornithine, DFMO as first-line treatment at this centre. The aim of this study was to determine the status of TbAT1 in recent isolates collected from T. b. gambiense sleeping sickness patients from Arua and Moyo districts in Northwestern Uganda after this shift in first-line drug choice. METHODOLOGY AND RESULTS: Blood and cerebrospinal fluids of consenting patients were collected for DNA preparation and subsequent amplification. All of the 105 isolates from Omugo that we successfully analysed by PCR-RFLP possessed the TbAT1 wild type allele. In addition, PCR/RFLP analysis was performed for 74 samples from Moyo, where melarsoprol is still the first line drug; 61 samples displayed the wild genotype while six were mutant and seven had a mixed pattern of both mutant and wild-type TbAT1. The melarsoprol treatment failure rate at Moyo over the same period was nine out of 101 stage II cases that were followed up at least once. Five of the relapse cases harboured mutant TbAT1, one had the wild type, while no amplification was achieved from the remaining three samples. CONCLUSIONS/SIGNIFICANCE: The apparent disappearance of mutant alleles at Omugo may correlate with melarsoprol withdrawal as first-line treatment. Our results suggest that melarsoprol could successfully be reintroduced following a time lag subsequent to its replacement. A field-applicable test to predict melarsoprol treatment outcome and identify

  2. [Serological evidence of the existence of a wild reservoir of Trypanosoma brucei gambiense in the Pendjari biosphere reservation in the Republic of Benin].

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    Guedegbe, B; Verhulst, A; Van Meirvenne, N; Pandey, V S; Doko, A

    1992-06-01

    In the national park of Pendjari, situated in the North-West of Benin, 91 wild animals, belonging to seven species, were darted. Thick and thin blood smears were examined for trypanosomes and plasma for trypanolytic antibodies against 6 antigenic variants of Trypanosoma brucei gambiense. Parasites were found in 13.92% and trypanolytic antibodies in 20.88% of the samples. A total of 28.57% of animals were positive by at least one of the two test systems used. Morphologically Trypanosoma congolense, T. vivax and T. brucei were identified. Overall prevalence was 40% in Adenota kob (n: 50), 13.63% in Alcelaphus buselaphus (n: 22), 10% in Hippotragus equinus (n: 10), 33% in Kobus defassa (n: 3), 0% in Phacochoerus aethiopicus (n: 3) and in Syncerus caffer (n: 2). The only lion (Panthera leo) examined was serologically positive. The results indicate that the wild animals are reservoirs of animal trypanosomes and suggest that among them Adenota kob and Panthera leo are carriers of T. brucei gambiense, one of the etiological aspects of human trypanosomiasis. PMID:1417158

  3. 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.

  4. Wild chimpanzees are infected by Trypanosoma brucei.

    Science.gov (United States)

    Jirků, Milan; Votýpka, Jan; Petrželková, Klára J; Jirků-Pomajbíková, Kateřina; Kriegová, Eva; Vodička, Roman; Lankester, Felix; Leendertz, Siv Aina J; Wittig, Roman M; Boesch, Christophe; Modrý, David; Ayala, Francisco J; Leendertz, Fabian H; Lukeš, Julius

    2015-12-01

    Although wild chimpanzees and other African great apes live in regions endemic for African sleeping sickness, very little is known about their trypanosome infections, mainly due to major difficulties in obtaining their blood samples. In present work, we established a diagnostic ITS1-based PCR assay that allows detection of the DNA of all four Trypanosoma brucei subspecies (Trypanosoma brucei brucei, Trypanosoma brucei rhodesiense, Trypanosoma brucei gambiense, and Trypanosoma brucei evansi) in feces of experimentally infected mice. Next, using this assay we revealed the presence of trypanosomes in the fecal samples of wild chimpanzees and this finding was further supported by results obtained using a set of primate tissue samples. Phylogenetic analysis of the ITS1 region showed that the majority of obtained sequences fell into the robust T. brucei group, providing strong evidence that these infections were caused by T. b. rhodesiense and/or T. b. gambiense. The optimized technique of trypanosome detection in feces will improve our knowledge about the epidemiology of trypanosomes in primates and possibly also other endangered mammals, from which blood and tissue samples cannot be obtained. 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. PMID:26110113

  5. 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.

  6. Role of expression site switching in the development of resistance to human Trypanosome Lytic Factor-1 in Trypanosoma brucei brucei.

    Science.gov (United States)

    Kieft, Rudo; Stephens, Natalie A; Capewell, Paul; MacLeod, Annette; Hajduk, Stephen L

    2012-05-01

    Human high-density lipoproteins (HDLs) play an important role in human innate immunity to infection by African trypanosomes with a minor subclass, Trypanosome Lytic Factor-1 (TLF-1), displaying highly selective cytotoxicity to the veterinary pathogen Trypanosoma brucei brucei but not against the human sleeping sickness pathogens Trypanosoma brucei gambiense or Trypanosoma brucei rhodesiense. T. b. rhodesiense has evolved the serum resistance associated protein (SRA) that binds and confers resistance to TLF-1 while T. b. gambiense lacks the gene for SRA indicating that these parasites have diverse mechanisms of resistance to TLF-1. Recently, we have shown that T. b. gambiense (group 1) resistance to TLF-1 correlated with the loss of the haptoglobin/hemoglobin receptor (HpHbR) expression, the protein responsible for high affinity binding and uptake of TLF-1. In the course of these studies we also examined TLF-1 resistant T. b. brucei cell lines, generated by long-term in vitro selection. We found that changes in TLF-1 susceptibility in T. b. brucei correlated with changes in variant surface glycoprotein (VSG) expression in addition to reduced TLF-1 binding and uptake. To determine whether the expressed VSG or expression site associated genes (ESAGs) contribute to TLF-1 resistance we prepared a TLF-1 resistant T. b. brucei with a selectable marker in a silent bloodstream expression site (BES). Drug treatment allowed rapid selection of trypanosomes that activated the tagged BES. These studies show that TLF-1 resistance in T. b. brucei is largely independent of the expressed VSG or ESAGs further supporting the central role of HpHbR expression in TLF-1 susceptibility in these cells. PMID:22226682

  7. 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.

  8. What happens when Trypanosoma brucei leaves Africa

    OpenAIRE

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

    2008-01-01

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

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

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    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. Identifying Transmission Cycles at the Human-Animal Interface: The Role of Animal Reservoirs in Maintaining Gambiense Human African Trypanosomiasis

    OpenAIRE

    Sebastian Funk; Hiroshi Nishiura; Hans Heesterbeek; W. John Edmunds; Francesco Checchi

    2013-01-01

    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 considere...

  12. 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.

  13. 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.

  14. 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.

  15. 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.

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

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    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

  17. 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 ...

  18. 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.

  19. Hidden Markov Models for Gene Sequence Classification: Classifying the VSG genes in the Trypanosoma brucei Genome

    OpenAIRE

    Mesa, Andrea; Basterrech, Sebastián; Guerberoff, Gustavo; Alvarez-Valin, Fernando

    2015-01-01

    The article presents an application of Hidden Markov Models (HMMs) for pattern recognition on genome sequences. We apply HMM for identifying genes encoding the Variant Surface Glycoprotein (VSG) in the genomes of Trypanosoma brucei (T. brucei) and other African trypanosomes. These are parasitic protozoa causative agents of sleeping sickness and several diseases in domestic and wild animals. These parasites have a peculiar strategy to evade the host's immune system that consists in periodicall...

  20. 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 ...

  1. 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.

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

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    Franco JR

    2012-08-01

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

  3. The lysosomotropic drug LeuLeu-OMe induces lysosome disruption and autophagy-independent cell death in Trypanosoma brucei

    OpenAIRE

    Hazel Xinyu Koh; Htay Mon Aye; Tan, Kevin S W; He, Cynthia Y.

    2015-01-01

    Background: Trypanosoma brucei is a blood-borne, protozoan parasite that causes African sleeping sickness in humans and nagana in animals. The current chemotherapy relies on only a handful of drugs that display undesirable toxicity, poor efficacy and drug-resistance. In this study, we explored the use of lysosomotropic drugs to induce bloodstream form T. brucei cell death via lysosome destabilization. Methods: We measured drug concentrations that inhibit cell proliferation by 50% (...

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

    OpenAIRE

    McCarroll, Charlotte S; Rossor, Charlotte L.; Linda R Morrison; Morrison, Liam J.; Loughrey, Christopher M.

    2015-01-01

    Author Summary African trypanosomiasis (AT) is a disease caused by the single-celled protozoan parasite Trypanosoma brucei. In humans, AT causes neurological problems including sleep disturbances, which give the disease its colloquial name of “sleeping sickness”. Much of the focus of AT research has been on the neurological deficits, but other major organs are also affected, including the heart. Previous studies in humans and animals with AT have identified heart abnormalities such as contrac...

  5. Comparative genomics of drug resistance in Trypanosoma brucei rhodesiense.

    Science.gov (United States)

    Graf, Fabrice E; Ludin, Philipp; Arquint, Christian; Schmidt, Remo S; Schaub, Nadia; Kunz Renggli, Christina; Munday, Jane C; Krezdorn, Jessica; Baker, Nicola; Horn, David; Balmer, Oliver; Caccone, Adalgisa; de Koning, Harry P; Mäser, Pascal

    2016-09-01

    Trypanosoma brucei rhodesiense is one of the causative agents of human sleeping sickness, a fatal disease that is transmitted by tsetse flies and restricted to Sub-Saharan Africa. Here we investigate two independent lines of T. b. rhodesiense that have been selected with the drugs melarsoprol and pentamidine over the course of 2 years, until they exhibited stable cross-resistance to an unprecedented degree. We apply comparative genomics and transcriptomics to identify the underlying mutations. Only few mutations have become fixed during selection. Three genes were affected by mutations in both lines: the aminopurine transporter AT1, the aquaporin AQP2, and the RNA-binding protein UBP1. The melarsoprol-selected line carried a large deletion including the adenosine transporter gene AT1, whereas the pentamidine-selected line carried a heterozygous point mutation in AT1, G430R, which rendered the transporter non-functional. Both resistant lines had lost AQP2, and both lines carried the same point mutation, R131L, in the RNA-binding motif of UBP1. The finding that concomitant deletion of the known resistance genes AT1 and AQP2 in T. b. brucei failed to phenocopy the high levels of resistance of the T. b. rhodesiense mutants indicated a possible role of UBP1 in melarsoprol-pentamidine cross-resistance. However, homozygous in situ expression of UBP1-Leu(131) in T. b. brucei did not affect the sensitivity to melarsoprol or pentamidine. PMID:26973180

  6. Ribose 5-Phosphate Isomerase B Knockdown Compromises Trypanosoma brucei Bloodstream Form Infectivity

    OpenAIRE

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

    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 dru...

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    Coleman Paul G

    2008-03-01

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

  9. Mapping of VSG similarities in Trypanosoma brucei

    OpenAIRE

    Weirather, Jason L.; Wilson, Mary E; Donelson, John E.

    2011-01-01

    The protozoan parasite Trypanosoma brucei switches its variant surface glycoprotein (VSG) to subvert its mammalian hosts’ immune responses. The T. brucei genome contains as many as 1600 VSG genes (VSGs), but most are silent noncoding pseudogenes. Only one functional VSG, located in a telomere-linked expression site, is transcribed at a time. Silent VSGs are copied into a VSG expression site through gene conversion. Truncated gene conversion events can generate new mosaic VSGs with segments of...

  10. Effects of tea on survival rates and liver pathology of Trypanosoma brucei brucei infected mice

    OpenAIRE

    Mbuthia, S.K; Wachira, N.W; Ngure, R.M; Ouma, J; Kagira, J. M.

    2011-01-01

    The current study investigated the effects of different types of Kenyan tea extracts on the pathogenesis ofTrypanosoma brucei brucei in a Swiss White mice model. Following infection with trypanosomes, the micewere monitored for survival and liver pathology. Tea significantly (P

  11. 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.

  12. Evaluation of the In Vitro Efficacy of Artemisia annua, Rumex abyssinicus, and Catha edulis Forsk Extracts in Cancer and Trypanosoma brucei Cells.

    Science.gov (United States)

    Worku, Netsanet; Mossie, Andualem; Stich, August; Daugschies, Arwid; Trettner, Susanne; Hemdan, Nasr Y A; Birkenmeier, Gerd

    2013-01-01

    The current drugs against sleeping sickness are derived from cancer chemotherapeutic approaches. Herein, we aimed at evaluating the in vitro effect of alcoholic extracts of Artemisia annua (AMR), Rumex abyssinicus (RMA), and Catha edulis Forsk (CEF) on proliferation/viability of 1321N1 astrocytoma, MCF-7 breast cancer, THP-1 leukemia, and LNCaP, Du-145, and PC-3 prostate cancer cells and on Trypanosoma brucei cells. Proliferation of tumor cells was evaluated by WST-1 assay and viability/behaviour of T. brucei by cell counting and light microscopy. CEF was the most efficient growth inhibitor in comparison to AMR and RMA. Nevertheless, in LNCaP and THP-1 cells, all extracts significantly inhibited tumor growth at 3 μg/mL. All extracts inhibited proliferation of T. brucei cells in a concentration-dependent manner. Microscopic analysis revealed that 95% of the T. brucei cells died when exposed to 33 μg/mL CEF for 3 hrs. Similar results were obtained using 33 μg/mL AMR for 6 hrs. In case of RMA, however, higher concentrations were necessary to obtain similar effects on T. brucei. This demonstrates the antitumor efficacy of these extracts as well as their ability to dampen viability and proliferation of T. brucei, suggesting a common mechanism of action on highly proliferative cells, most probably by targeting cell metabolism. PMID:25937964

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

    OpenAIRE

    Georges C. Accrombessi; Jacques Poupaert; Raymond H. Fatondji; Salomé D. S. Kpoviessi; Gbaguidi, Fernand A.; Bienvenu Glinma

    2011-01-01

    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 a...

  14. 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

  15. 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,

  16. Sleep and Women

    Science.gov (United States)

    ... Sleep Debt Sleep Deprivation Sleep Disorders Sleep history Sleep hygiene sleep length Sleep Need Sleep talking Sleeping Pills ... culture Immune System military travel CDC Healthy Sleep Sleep hygiene sleep length Sleep Debt Sleep Deprivation Sleep Need ...

  17. Cell cycle regulation in Trypanosoma brucei

    OpenAIRE

    Tansy C Hammarton

    2007-01-01

    Cell division is regulated by intricate and interconnected signal transduction pathways that precisely coordinate, in time and space, the complex series of events involved in replicating and segregating the component parts of the cell. In Trypanosoma brucei, considerable progress has been made over recent years in identifying molecular regulators of the cell cycle and elucidating their functions, although many regulators undoubtedly remain to be identified, and there is still a long way to go...

  18. 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

  19. Human African Trypanosomiasis Transmission, Kinshasa, Democratic Republic of Congo

    Science.gov (United States)

    Diabakana, Philemon Mansinsa; Mesu, Victor Kande Betu Ku; Manzambi, Emile Zola; Ollivier, Gaelle; Asonganyi, Tazoacha; Cuny, Gerard; Grébaut, Pascal

    2006-01-01

    To investigate the epidemiology of human African trypanosomiasis (sleeping sickness) in Kinshasa, Democratic Republic of Congo, 2 entomologic surveys were conducted in 2005. Trypanosoma brucei gambiense and human-blood meals were found in tsetse fly midguts, which suggested active disease transmission. Vector control should be used to improve human African trypanosomiasis control efforts. PMID:17326955

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

    Science.gov (United States)

    Munday, Jane C.; Tagoe, Daniel N. A.; Stelmanis, Valters; Schnaufer, Achim

    2016-01-01

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

  1. 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.

  2. Evaluation of the In Vitro Efficacy of Artemisia annua, Rumex abyssinicus, and Catha edulis Forsk Extracts in Cancer and Trypanosoma brucei Cells

    OpenAIRE

    Netsanet Worku; Andualem Mossie; August Stich; Arwid Daugschies; Susanne Trettner; Hemdan, Nasr Y. A.; Gerd Birkenmeier

    2013-01-01

    The current drugs against sleeping sickness are derived from cancer chemotherapeutic approaches. Herein, we aimed at evaluating the in vitro effect of alcoholic extracts of Artemisia annua (AMR), Rumex abyssinicus (RMA), and Catha edulis Forsk (CEF) on proliferation/viability of 1321N1 astrocytoma, MCF-7 breast cancer, THP-1 leukemia, and LNCaP, Du-145, and PC-3 prostate cancer cells and on Trypanosoma brucei cells. Proliferation of tumor cells was evaluated by WST-1 assay and viability/behav...

  3. Mapping of VSG similarities in Trypanosoma brucei.

    Science.gov (United States)

    Weirather, Jason L; Wilson, Mary E; Donelson, John E

    2012-02-01

    The protozoan parasite Trypanosoma brucei switches its variant surface glycoprotein (VSG) to subvert its mammalian hosts' immune responses. The T. brucei genome contains as many as 1600 VSG genes (VSGs), but most are silent noncoding pseudogenes. Only one functional VSG, located in a telomere-linked expression site, is transcribed at a time. Silent VSGs are copied into a VSG expression site through gene conversion. Truncated gene conversion events can generate new mosaic VSGs with segments of sequence identity to other VSGs. To examine the VSG family sub-structure within which these events occur, we combined the available VSG sequences and annotations with scripted BLAST searches to map the relationships among VSGs in the T. brucei genome. Clusters of related VSGs were visualized in 2- and 3-dimensions for different N- and C-terminal regions. Five types of N-termini (N1-N5) were observed, within which gene recombinational events are likely to occur, often with fully-coding 'functional' or 'atypical'VSGs centrally located between more dissimilar VSGs. Members of types N1, N3 and N4 are most closely related in the middle of the N-terminal region, whereas type N2 members are more similar near the N-terminus. Some preference occurs in pairing between specific N- and C-terminal types. Statistical analyses indicated no overall tendency for more related VSGs to be located closer in the genome than less related VSGs, although exceptions were noted. Many potential mosaic gene formation events within each N-terminal type were identified, contrasted by only one possible mosaic gene formation between N-terminal types (N1 and N2). These data suggest that mosaic gene formation is a major contributor to the overall VSG diversity, even though gene recombinational events between members of different N-terminal types occur only rarely. PMID:22079099

  4. 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.

  5. 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.

  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. A comparative study on the susceptibility of male and female albino mice to Trypanosoma brucei brucei

    Directory of Open Access Journals (Sweden)

    A.A. Turay, G.O. Nwobu, G.R.A. Okogun, C.U. Igwe, K. Adeyeye, K.E. Aghatise, H.O. Okpal & Y.M. Tatfeng

    2005-03-01

    Full Text Available Background & objectives: Trypanosomiasis has remained a major set-back in the development oflivestock farming in tropical Africa. Thus the need for ascertaining the trypanotolerant levels ofdomestic animal breeds and possible improvement on them cannot be over-emphasised.Methods: Level of trypanotolerance in animals was compared between sexes using albino mice infectedwith a Nigerian strain of Trypanosoma brucei brucei at a 50% mouse lethal dose (MLD50.Results: The male mice showed unrestrained parasite growth with a prepatent period (PP of two daysand a mean survival period (MSP of six days corresponding to a gradual decrease in packed cellvolume (PCV, body weight, diet response and white blood cells (WBC count to the time of death.Their female counterparts showed a PP of three days and MSP of ten days with a similar PCV gradientbut a refractory WBC count. There was no significant difference in the differential leucocytes countin both sexes. However, the eosinophils count was significantly higher in the infected animals. It wasfound that female albino mice exercised more parasite restraint than their male counterparts.Interpretation & conclusion: The result suggests that the female animals may be more trypanotoleranthence may be more useful in protein production in trypanosomiasis endemic areas. However, furtherresearch using large domestic breeds like goats and sheep may be required to confirm the hypothesis.

  8. 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.

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

    Science.gov (United States)

    Habila, Nathan; Agbaji, Abel S; Ladan, Zakari; Bello, Isaac A; Haruna, Emmanuel; Dakare, Monday A; Atolagbe, Taofiq O

    2010-01-01

    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. PMID:20700425

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

    Science.gov (United States)

    Habila, Nathan; Agbaji, Abel S.; Ladan, Zakari; Bello, Isaac A.; Haruna, Emmanuel; Dakare, Monday A.; Atolagbe, Taofiq O.

    2010-01-01

    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. PMID:20700425

  11. Triacylglycerol Storage in Lipid Droplets in Procyclic Trypanosoma brucei.

    Science.gov (United States)

    Allmann, Stefan; Mazet, Muriel; Ziebart, Nicole; Bouyssou, Guillaume; Fouillen, Laetitia; Dupuy, Jean-William; Bonneu, Marc; Moreau, Patrick; Bringaud, Frédéric; Boshart, Michael

    2014-01-01

    Carbon storage is likely to enable adaptation of trypanosomes to nutritional challenges or bottlenecks during their stage development and migration in the tsetse. Lipid droplets are candidates for this function. This report shows that feeding of T. brucei with oleate results in a 4-5 fold increase in the number of lipid droplets, as quantified by confocal fluorescence microscopy and by flow cytometry of BODIPY 493/503-stained cells. The triacylglycerol (TAG) content also increased 4-5 fold, and labeled oleate is incorporated into TAG. Fatty acid carbon can thus be stored as TAG in lipid droplets under physiological growth conditions in procyclic T. brucei. β-oxidation has been suggested as a possible catabolic pathway for lipids in T. brucei. A single candidate gene, TFEα1 with coding capacity for a subunit of the trifunctional enzyme complex was identified. TFEα1 is expressed in procyclic T. brucei and present in glycosomal proteomes, Unexpectedly, a TFEα1 gene knock-out mutant still expressed wild-type levels of previously reported NADP-dependent 3-hydroxyacyl-CoA dehydrogenase activity, and therefore, another gene encodes this enzymatic activity. Homozygous Δtfeα1/Δtfeα1 null mutant cells show a normal growth rate and an unchanged glycosomal proteome in procyclic T. brucei. The decay kinetics of accumulated lipid droplets upon oleate withdrawal can be fully accounted for by the dilution effect of cell division in wild-type and Δtfeα1/Δtfeα1 cells. The absence of net catabolism of stored TAG in procyclic T. brucei, even under strictly glucose-free conditions, does not formally exclude a flux through TAG, in which biosynthesis equals catabolism. Also, the possibility remains that TAG catabolism is completely repressed by other carbon sources in culture media or developmentally activated in post-procyclic stages in the tsetse. PMID:25493940

  12. Triacylglycerol Storage in Lipid Droplets in Procyclic Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Stefan Allmann

    Full Text Available Carbon storage is likely to enable adaptation of trypanosomes to nutritional challenges or bottlenecks during their stage development and migration in the tsetse. Lipid droplets are candidates for this function. This report shows that feeding of T. brucei with oleate results in a 4-5 fold increase in the number of lipid droplets, as quantified by confocal fluorescence microscopy and by flow cytometry of BODIPY 493/503-stained cells. The triacylglycerol (TAG content also increased 4-5 fold, and labeled oleate is incorporated into TAG. Fatty acid carbon can thus be stored as TAG in lipid droplets under physiological growth conditions in procyclic T. brucei. β-oxidation has been suggested as a possible catabolic pathway for lipids in T. brucei. A single candidate gene, TFEα1 with coding capacity for a subunit of the trifunctional enzyme complex was identified. TFEα1 is expressed in procyclic T. brucei and present in glycosomal proteomes, Unexpectedly, a TFEα1 gene knock-out mutant still expressed wild-type levels of previously reported NADP-dependent 3-hydroxyacyl-CoA dehydrogenase activity, and therefore, another gene encodes this enzymatic activity. Homozygous Δtfeα1/Δtfeα1 null mutant cells show a normal growth rate and an unchanged glycosomal proteome in procyclic T. brucei. The decay kinetics of accumulated lipid droplets upon oleate withdrawal can be fully accounted for by the dilution effect of cell division in wild-type and Δtfeα1/Δtfeα1 cells. The absence of net catabolism of stored TAG in procyclic T. brucei, even under strictly glucose-free conditions, does not formally exclude a flux through TAG, in which biosynthesis equals catabolism. Also, the possibility remains that TAG catabolism is completely repressed by other carbon sources in culture media or developmentally activated in post-procyclic stages in the tsetse.

  13. 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 ...

  14. 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 - ...

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

    Directory of Open Access Journals (Sweden)

    Trimpalis Philip

    2011-07-01

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

  16. Testicular pathology, gonadal and epididymal sperm reserves of Yankasa rams infected with experimental Trypanosoma brucei brucei and Trypanosoma evansi

    Science.gov (United States)

    Wada, Yunusa A.; Oniye, Sonnie J.; Rekwot, Peter I.; Okubanjo, Oluyinka O.

    2016-01-01

    Aim: The study was conducted to evaluate the pathological effects of trypanosomosis on the testes, gonadal, and epididymal sperm reserves of Yankasa rams for 98 days. Materials and Methods: A total of 16 Yankasa rams, aged between 24 and 30 months and weighed between 22 and 25 kg, were acclimatized for a period of 2-months in a clean fly proof house and were adequately fed and given water ad-libitum. Of the 16 rams, 12 that were clinically fit for the experiment at the end of the acclimatization period were randomly divided into four groups: Groups I, II, III, and IV, each having 3 rams. Groups I and II were each challenged singly with experimental Trypanosoma brucei brucei (Federer strain) and Trypanosoma evansi (Sokoto strain), respectively, while Group III was challenged with mixed T. brucei brucei and T. evansi parasites (50% of each species in the infective inoculum) and Group IV was left as an uninfected control. Each infected ram received 2 mL of the infected blood containing 2×106 trypomastigotes via the jugular vein, while the control group received 2 mL each, normal saline. Results: All the infected rams developed clinical signs typical of trypanosomosis at varying pre-patent periods. The gross lesions observed in the infected rams in Group II were moderate and more severe in those of Groups I and III. Histological sections of the testes of infected rams (Groups I, II, and III) showed moderate (T. evansi-infected group) to severe (mixed and T. brucei brucei-infected groups) testicular degenerations with reduction in number of spermatogenic cell layers, degenerated seminiferous tubules, congested interlobular spaces, loss of tissue architecture with significant (p<0.01) depletion, and loss of gonadal and epididymal sperm reserves in Groups I and III in comparison to Group II and the control Group IV. No observable clinical signs and histopathological lesions were found in those rams of the control Group IV. Conclusion: The study concluded that

  17. Testicular pathology, gonadal and epididymal sperm reserves of Yankasa rams infected with experimental Trypanosoma brucei brucei and Trypanosoma evansi

    Directory of Open Access Journals (Sweden)

    Yunusa A. Wada

    2016-07-01

    Full Text Available Aim: The study was conducted to evaluate the pathological effects of trypanosomosis on the testes, gonadal, and epididymal sperm reserves of Yankasa rams for 98 days. Materials and Methods: A total of 16 Yankasa rams, aged between 24 and 30 months and weighed between 22 and 25 kg, were acclimatized for a period of 2-months in a clean fly proof house and were adequately fed and given water ad-libitum. Of the 16 rams, 12 that were clinically fit for the experiment at the end of the acclimatization period were randomly divided into four groups: Groups I, II, III, and IV, each having 3 rams. Groups I and II were each challenged singly with experimental Trypanosoma brucei brucei (Federer strain and Trypanosoma evansi (Sokoto strain, respectively, while Group III was challenged with mixed T. brucei brucei and T. evansi parasites (50% of each species in the infective inoculum and Group IV was left as an uninfected control. Each infected ram received 2 mL of the infected blood containing 2×106 trypomastigotes via the jugular vein, while the control group received 2 mL each, normal saline. Results: All the infected rams developed clinical signs typical of trypanosomosis at varying pre-patent periods. The gross lesions observed in the infected rams in Group II were moderate and more severe in those of Groups I and III. Histological sections of the testes of infected rams (Groups I, II, and III showed moderate (T. evansi-infected group to severe (mixed and T. brucei brucei-infected groups testicular degenerations with reduction in number of spermatogenic cell layers, degenerated seminiferous tubules, congested interlobular spaces, loss of tissue architecture with significant (p<0.01 depletion, and loss of gonadal and epididymal sperm reserves in Groups I and III in comparison to Group II and the control Group IV. No observable clinical signs and histopathological lesions were found in those rams of the control Group IV. Conclusion: The study concluded

  18. Nanomolar Inhibitors of Trypanosoma brucei RNA Triphosphatase

    Directory of Open Access Journals (Sweden)

    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.

  19. Sleep apnoea

    OpenAIRE

    Jun, Jonathan C.; Swati Chopra; Schwartz, Alan R.

    2016-01-01

    Sleep apnoea is a disorder characterised by repetitive pauses in breathing during sleep caused by airway occlusion (obstructive sleep apnoea) or altered control of breathing (central sleep apnoea). In this Clinical Year in Review, we summarise high-impact research from the past year pertaining to management, diagnosis and cardio-metabolic consequences of sleep apnoea.

  20. 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.

  1. 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.

  2. 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. ...

  3. Challenges in Diagnosing Human African Trypanosomiasis: Evaluation of the MSF OCG project in Dingila, DRC

    OpenAIRE

    Van Nieuwenhove, Simon

    2015-01-01

    Between late 2010 and the end of 2014 and under extremely difficult conditions, Médecins sans Frontières (MSF) carried out a project to combat Human African Trypanosomiasis (HAT), also known as sleeping sickness, in the Dingila, Ango and Zobia regions of Orientale Province in the Democratic Republic of Congo (DRC). HAT in DRC is caused by Trypanosoma brucei gambiense and is transmitted by the tsetse fly (Glossina genus) of the Palpalis group. Without effective treatment, virtually all f...

  4. 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...

  5. [Sleep psychiatry].

    Science.gov (United States)

    Chiba, Shigeru

    2013-01-01

    Sleep disorders are serious issues in modern society. There has been marked scientific interest in sleep for a century, with the discoveries of the electrical activity of the brain (EEG), sleep-wake system, rapid eye movement (REM) sleep, and circadian rhythm system. Additionally, the advent of video-polysomnography in clinical research has revealed some of the consequences of disrupted sleep and sleep deprivation in psychiatric disorders. Decades of clinical research have demonstrated that sleep disorders are intimately tied to not only physical disease (e. g., lifestyle-related disease) but psychiatric illness. According to The International Classification of Sleep Disorders (2005), sleep disorders are classified into 8 major categories: 1) insomnia, 2) sleep-related breathing disorders, 3) hypersomnias of central origin, 4) circadian rhythm sleep disorders, 5) parasomnias, 6) sleep-related movement disorders, 7) isolated symptoms, and 8) other sleep disorders. Several sleep disorders, including obstructive sleep apnea syndrome, restless legs syndrome, periodic limb movement disorder, sleepwalking, REM sleep behavior disorder, and narcolepsy, may be comorbid or possibly mimic numerous psychiatric disorders, and can even occur due to psychiatric pharmacotherapy. Moreover, sleep disorders may exacerbate underlying psychiatric disorders when left untreated. Therefore, psychiatrists should pay attention to the intimate relationship between sleep disorders and psychiatric symptoms. Sleep psychiatry is an academic field focusing on interrelations between sleep medicine and psychiatry. This mini-review summarizes recent findings in sleep psychiatry. Future research on the bidirectional relation between sleep disturbance and psychiatric symptoms will shed light on the pathophysiological view of psychiatric disorders and sleep disorders. PMID:24050022

  6. Pentatricopeptide repeat proteins in Trypanosoma brucei function in mitochondrial ribosomes

    OpenAIRE

    Pusnik, Mascha; Small, Ian; Read, Laurie K.; Fabbro, Thomas; Schneider, André

    2008-01-01

    The pentatricopeptide repeat (PPR), a degenerate 35-amino-acid motif, defines a novel eukaryotic protein family. Plants have 400 to 500 distinct PPR proteins, whereas other eukaryotes generally have fewer than 5. The few PPR proteins that have been studied have roles in organellar gene expression, probably via direct interaction with RNA. Here we show that the parasitic protozoan Trypanosoma brucei encodes 28 distinct PPR proteins, an extraordinarily high number for a nonplant organism. A com...

  7. 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.

  8. 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.

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

    OpenAIRE

    Nwoha Rosemary Ijeoma Ogechi; Omamegbe Joseph Omalathebu

    2016-01-01

    Objective: To determine the effect of Trypanosoma 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 with T. brucei and treated with diminazene aceturate, and Group C was infected with T. brucei and treated with imidocarb dipropionate. Blood samples were collected from the media canthus of the experimental rats on ...

  10. 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.

  11. T cells and macrophages in Trypanosoma brucei-related glomerulopathy.

    Science.gov (United States)

    van Velthuysen, M L; Mayen, A E; van Rooijen, N; Fleuren, G J; de Heer, E; Bruijn, J A

    1994-08-01

    In a previous study, susceptibility for Trypanosoma brucei-related glomerulopathy in mice was shown to be dependent on non-major histocompatibility complex genes. Glomerular disease in this model could not be explained by the production of autoantibodies alone. In order to analyze which part of the defense system, in addition to the B-cell compartment, is involved in the development of this infection-related glomerular disease, groups of athymic (BALB/c rnu/rnu), splenectomized, or macrophage-depleted BALB/c mice were inoculated with T. brucei parasites. Polyclonal B-cell activation, invariably observed in infected BALB/c mice, was absent in BALB/c rnu/rnu mice. Glomerular disease in athymic mice, however, as defined by albuminuria and deposition of immune complexes, was not different from that seen in euthymic infected BALB/c mice. Splenectomy prior to inoculation of parasites led to a decreased incidence of albuminuria in 40% of the animals, whereas splenectomy 21 days after inoculation reduced albuminuria significantly, suggesting a role for spleen cells in the induction of glomerular disease. After macrophage depletion with liposome-encapsulated dichlorodimethylene-diphosphonate, infected BALB/c mice developed significantly higher albuminuria levels for a period up to 2 weeks after depletion. Therefore, it was concluded that the development of T. brucei-related glomerular disease is independent of thymus-matured T cells, while the involvement of macrophages in the development of proteinuria is inhibitory rather than disease inducing. Spleen cells other than thymus-dependent T cells, B cells, and macrophages should be investigated for their role in the pathogenesis of this glomerulopathy. PMID:7913696

  12. 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

  13. VSG gene expression site control in insect form Trypanosoma brucei.

    OpenAIRE

    Rudenko, G; Blundell, P A; Taylor, M. C.; Kieft, R.; Borst, P

    1994-01-01

    When the African trypanosome Trypanosoma brucei is taken up from mammals by a tse-tse fly, it replaces its variant surface glycoprotein (VSG) coat by a procyclin coat. Transcription of VSG genes stops in the fly, but transcription of sequences derived from the promoter area of the VSG expression site(s) remains high. Whether this is due to continuing high activity of one promoter or to low activity of many promoters was unclear. We have used the small differences between the sequences of diff...

  14. Healthy Sleep Habits

    Science.gov (United States)

    ... Sleep Apnea Testing CPAP Healthy Sleep Habits Healthy Sleep Habits Your behaviors can have a major impact ... team at an AASM accredited sleep center. Quick Sleep Tips Follow these tips to establish healthy sleep ...

  15. Obstructive Sleep Apnea

    Science.gov (United States)

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

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

    KAUST Repository

    Wang, Jingyan

    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.

  17. Sleeping sickness

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001362.htm Sleeping sickness To use the sharing features on this page, please enable JavaScript. Sleeping sickness is an infection caused by germs carried ...

  18. Exercise & Sleep

    Science.gov (United States)

    ... Feature: Back to School, the Healthy Way Exercise & Sleep Past Issues / Fall 2012 Table of Contents At ... healthy weight Build sturdy muscles, bones, and joints Sleep better at night More time in front of ...

  19. 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 ...

  20. Sleep apnoea

    OpenAIRE

    Hensley, Michael; Ray, Cheryl

    2009-01-01

    Sleep apnoea is the popular term for obstructive sleep apnoea-hypopnoea syndrome (OSAHS). OSAHS is abnormal breathing during sleep that causes recurrent arousals, sleep fragmentation, daytime sleepiness, and nocturnal hypoxaemia. Apnoea may be "central", in which there is cessation of inspiratory effort, or "obstructive", in which inspiratory efforts continue but are ineffective because of upper airway obstruction.OSAHS affects up to 4% of men and 2% of women in the USA, with obesity being...

  1. Effects of DMSO on Diminazene Efficacy in Experimental Murine T. brucei Infection

    OpenAIRE

    K.I. Eghianruwa; Anika, S.M.

    2012-01-01

    This study evaluated the influence of dimethyl sulfoxide (DMSO) daily supplementation on diminazene treatment of trypanosomosis. Four groups of Trypanosoma brucei brucei infected rats received 7.0 mg/kg diminazene aceturate on day 7 post infection. Three of the four groups received different doses of DMSO (0.5, 1.0 and 2.0 g/kg, respectively) in addition to diminazene treatment. The changes in hematological parameters and the weights of liver, spleen and heart caused by T. brucei infection we...

  2. 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.

  3. Why Sleep?

    OpenAIRE

    Manoach, Dara S.; Stickgold, Robert

    2013-01-01

    We human beings spend about a third of our lives sleeping. That means that if you live to 90, you'll sleep for about 30 years – probably more time than you'll spend doing anything else. Sleep is really important since we cannot live without it and spend so much time doing it. Yet unlike the other basic biological drives such as eating and reproducing, we still don't understand exactly why we need to sleep. It used to be thought that sleep was mainly to rest and restore the body and the mind, ...

  4. 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.

  5. Simulating the complex cell design of Trypanosoma brucei and its motility.

    Directory of Open Access Journals (Sweden)

    Davod Alizadehrad

    2015-01-01

    Full Text Available The flagellate Trypanosoma brucei, which causes the sleeping sickness when infecting a mammalian host, goes through an intricate life cycle. It has a rather complex propulsion mechanism and swims in diverse microenvironments. These continuously exert selective pressure, to which the trypanosome adjusts with its architecture and behavior. As a result, the trypanosome assumes a diversity of complex morphotypes during its life cycle. However, although cell biology has detailed form and function of most of them, experimental data on the dynamic behavior and development of most morphotypes is lacking. Here we show that simulation science can predict intermediate cell designs by conducting specific and controlled modifications of an accurate, nature-inspired cell model, which we developed using information from live cell analyses. The cell models account for several important characteristics of the real trypanosomal morphotypes, such as the geometry and elastic properties of the cell body, and their swimming mechanism using an eukaryotic flagellum. We introduce an elastic network model for the cell body, including bending rigidity and simulate swimming in a fluid environment, using the mesoscale simulation technique called multi-particle collision dynamics. The in silico trypanosome of the bloodstream form displays the characteristic in vivo rotational and translational motility pattern that is crucial for survival and virulence in the vertebrate host. Moreover, our model accurately simulates the trypanosome's tumbling and backward motion. We show that the distinctive course of the attached flagellum around the cell body is one important aspect to produce the observed swimming behavior in a viscous fluid, and also required to reach the maximal swimming velocity. Changing details of the flagellar attachment generates less efficient swimmers. We also simulate different morphotypes that occur during the parasite's development in the tsetse fly, and

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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 ...

  13. 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- ... Rate This Content: NEXT >> Updated: February 22, 2012 Sleep Infographic Sleep Disorders & Insufficient Sleep: Improving Health through ...

  14. National Sleep Foundation

    Science.gov (United States)

    ... Turkish Ukrainian Urdu Vietnamese Welsh Yiddish Choose a Sleep Topic sleep.org Sleep Disorders View More Items ... it. More Join Now Become a Professional Member Sleep.org Footer Redirect Learn about how sleep impacts ...

  15. 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 ( ...

  16. 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.

  17. 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].

  18. 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 ...

  19. 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

  20. 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.

  1. Sleep Quiz

    Science.gov (United States)

    ... and mental conditions and stress. Insomnia is the perception that you don't get enough sleep because ... RLS) is a medical condition distinguished by tingling sensations in the legs--and sometimes the arms--while ...

  2. Sleeping during Pregnancy

    Science.gov (United States)

    ... Tropical Delight: Melon Smoothie Pregnant? Your Baby's Growth Sleeping During Pregnancy KidsHealth > For Parents > Sleeping During Pregnancy ... have trouble getting enough deep, uninterrupted sleep. Why Sleeping Can Be Difficult The first and most pressing ...

  3. Sleep and Newborns

    Science.gov (United States)

    ... Story" 5 Things to Know About Zika & Pregnancy Sleep and Newborns KidsHealth > For Parents > Sleep and Newborns ... night it is. How Long Will My Newborn Sleep? A newborn may sleep up to 18 hours ...

  4. Sleep Apnea Information Page

    Science.gov (United States)

    ... Awards Enhancing Diversity Find People About NINDS NINDS Sleep Apnea Information Page Table of Contents (click to ... en Español Additional resources from MedlinePlus What is Sleep Apnea? Sleep apnea is a common sleep disorder ...

  5. 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 ...

  6. Sleep Apnea (For Parents)

    Science.gov (United States)

    ... 5 Things to Know About Zika & Pregnancy 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 ...

  7. Sleep Talking (Somniloquy)

    Science.gov (United States)

    ... Facts Causes and Risk Factors Diagnosis and Treatment Sleepwalking Overview & Facts Symptoms & Risk Factors Diagnosis & Treatment Sleep ... area. Search radius: Email Print Parasomnias Confusional Arousals Sleepwalking Sleep Terrors Sleep Eating Disorder REM Sleep Behavior ...

  8. 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 ...

  9. 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

  10. Refreshing Sleep and Sleep Continuity Determine Perceived Sleep Quality

    Science.gov (United States)

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

    2016-01-01

    Sleep quality is a construct often measured, employed as an outcome criterion for therapeutic success, but never defined. In two studies we examined appraised good and poor sleep quality in three groups: a control group, individuals with obstructive sleep apnea, and those with insomnia disorder. In Study 1 we used qualitative methodology to examine good and poor sleep quality in 121 individuals. In Study 2 we examined sleep quality in 171 individuals who had not participated in Study 1 and evaluated correlates and predictors of sleep quality. Across all six samples and both qualitative and quantitative methodologies, the daytime experience of feeling refreshed (nonrefreshed) in the morning and the nighttime experience of good (impaired) sleep continuity characterized perceived good and poor sleep. Our results clarify sleep quality as a construct and identify refreshing sleep and sleep continuity as potential clinical and research outcome measures. PMID:27413553

  11. Electroencephalographic studies of sleep

    Science.gov (United States)

    Webb, W. B.; Agnew, H. W., Jr.

    1975-01-01

    Various experimental studies on sleep are described. The following areas are discussed: (1) effect of altered day length on sleep, (2) effect of a partial loss of sleep on subsequent nocturnal sleep; (3) effect of rigid control over sleep-wake-up times; (4) sleep and wakefulness in a time-free environment; (5) distribution of spindles during a full night of sleep; and (6) effect on sleep and performance of swiftly changing shifts of work.

  12. Sleep in Othello

    OpenAIRE

    Dimsdale, Joel E.

    2009-01-01

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

  13. 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.

  14. Refreshing Sleep and Sleep Continuity Determine Perceived Sleep Quality

    OpenAIRE

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

    2016-01-01

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

  15. The dispersal ecology of Rhodesian sleeping sickness following its introduction to a new area.

    Directory of Open Access Journals (Sweden)

    Nicola A Wardrop

    Full Text Available Tsetse-transmitted human and animal trypanosomiasis are constraints to both human and animal health in sub-Saharan Africa, and although these diseases have been known for over a century, there is little recent evidence demonstrating how the parasites circulate in natural hosts and ecosystems. The spread of Rhodesian sleeping sickness (caused by Trypanosoma brucei rhodesiense within Uganda over the past 15 years has been linked to the movement of infected, untreated livestock (the predominant reservoir from endemic areas. However, despite an understanding of the environmental dependencies of sleeping sickness, little research has focused on the environmental factors controlling transmission establishment or the spatially heterogeneous dispersal of disease following a new introduction. In the current study, an annually stratified case-control study of Rhodesian sleeping sickness cases from Serere District, Uganda was used to allow the temporal assessment of correlations between the spatial distribution of sleeping sickness and landscape factors. Significant relationships were detected between Rhodesian sleeping sickness and selected factors, including elevation and the proportion of land which was "seasonally flooding grassland" or "woodlands and dense savannah." Temporal trends in these relationships were detected, illustrating the dispersal of Rhodesian sleeping sickness into more 'suitable' areas over time, with diminishing dependence on the point of introduction in concurrence with an increasing dependence on environmental and landscape factors. These results provide a novel insight into the ecology of Rhodesian sleeping sickness dispersal and may contribute towards the implementation of evidence-based control measures to prevent its further spread.

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    Rommie E Amaro

    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.

  6. 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.

  7. Genetics of Sleep and Sleep disorders

    OpenAIRE

    Sehgal, Amita; Mignot, Emmanuel

    2011-01-01

    Sleep remains one of the least understood phenomena in biology – even its role in synaptic plasticity remains debatable. Since sleep was recognized to be regulated genetically, intense research has launched on two fronts: the development of model organisms for deciphering the molecular mechanisms of sleep and attempts to identify genetic underpinnings of human sleep disorders. In this Review, we describe how unbiased, high-throughput screens in model organisms are uncovering sleep regulatory ...

  8. 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...

  9. Sleep in Neurodegenerative Diseases.

    Science.gov (United States)

    Iranzo, Alex

    2016-03-01

    Disorders of sleep are an integral part of neurodegenerative diseases and include insomnia, sleep-wake cycle disruption, excessive daytime sleepiness that may be manifested as persistent somnolence or sudden onset of sleep episodes, obstructive and central sleep apnea, rapid eye movement sleep behavior disorder, and restless legs syndrome. The origin of these sleep disorders is multifactorial including degeneration of the brain areas that modulate sleep, the symptoms of the disease, and the effect of medications. Treatment of sleep disorders in patients with neurodegenerative diseases should be individualized and includes behavioral therapy, sleep hygiene, bright light therapy, melatonin, hypnotics, waking-promoting agents, and continuous positive airway pressure. PMID:26972029

  10. What Is Sleep Apnea?

    Science.gov (United States)

    ... move out of deep sleep and into light sleep. As a result, the quality of your sleep is poor, which makes you tired during the ... of silence followed by gasps. Wanting a better quality of life, Jim sought the advice of his doctor, who recommended a sleep study. As a result of the sleep study, ...

  11. Snoring and Sleep Apnea

    Science.gov (United States)

    ... experience sleepless nights and fatigue. Medically – It disturbs sleeping patterns and deprives the snorer of adequate rest. It ... snacks for three hours before retiring. • Establish regular sleeping patterns. • Sleep on your side rather than your back. • ...

  12. Problems sleeping during pregnancy

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000559.htm Problems sleeping during pregnancy To use the sharing features on ... time sleeping well. Why is it hard to sleep during pregnancy? Your baby is growing bigger, which ...

  13. 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 ...

  14. 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 ...

  15. Sleep studies (image)

    Science.gov (United States)

    During a sleep study the sleep cycles and stages of sleep are monitored. Electrodes are placed to monitor continuous recordings of brain waves, electrical activity of muscles, eye movement, respiratory ...

  16. Do placebos alter sleep?

    Science.gov (United States)

    Adam, K; Adamson, L; Brezinová, V; Oswald, I

    1976-01-24

    Deliberate suggestion that an inert capsule was a sleeping pill was found not to influence subjective ratings of sleep quality or anxiety or the electrophysiologically recorded features of sleep in 10 volunteers aged 41-62 years. PMID:1247770

  17. Do placebos alter sleep?

    Science.gov (United States)

    Adam, K; Adamson, L; Brezinová, V; Oswald, I

    1976-01-24

    Deliberate suggestion that an inert capsule was a sleeping pill was found not to influence subjective ratings of sleep quality or anxiety or the electrophysiologically recorded features of sleep in 10 volunteers aged 41-62 years.

  18. American Sleep Association

    Science.gov (United States)

    ... Public Health Professionals Join ASA Press Room American Sleep Association Improving public health by increasing awareness about ... Members Username or Email Password Remember Me Register Sleep Blog Let’s Teach Our Children About Sleep How ...

  19. Sleep Apnea Detection

    Science.gov (United States)

    ... Prenatal Baby Bathing & Skin Care Breastfeeding Crying & Colic Diapers & Clothing Feeding & Nutrition Preemie Sleep Teething & Tooth Care Toddler Preschool Gradeschool Teen Young Adult Healthy Children > Ages & Stages > Baby > Sleep > Sleep Apnea ...

  20. Sleep Troubles, Heart Troubles?

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_161037.html Sleep Troubles, Heart Troubles? American Heart Association says it's ... 19, 2016 MONDAY, Sept. 19, 2016 (HealthDay News) -- Sleep disorders -- including too little or too much sleep -- ...

  1. Aging changes in sleep

    Science.gov (United States)

    ... a health care provider to find out whether depression or another health condition is affecting your sleep. COMMON PROBLEMS Insomnia is one of the more common sleep problems in the elderly. Other sleep disorders , such as restless legs syndrome, ...

  2. Identification of a Wee1-like kinase gene essential for procyclic Trypanosoma brucei survival.

    Directory of Open Access Journals (Sweden)

    Natalia Y Boynak

    Full Text Available Regulation of eukaryotic cell cycle progression requires sequential activation and inactivation of cyclin-dependent kinases (CDKs. Activation of the cyclin B-cdc2 kinase complex is a pivotal step in mitotic initiation and the tyrosine kinase Wee1 is a key regulator of cell cycle sequence during G2/M transition and inhibits mitotic entry by phosphorylating the inhibitory tyrosine 15 on the cdc2 M-phase-inducing kinase. Wee1 degradation is essential for the exit from the G2 phase. In trypanosomatids, little is known about the genes that regulate cyclin B-cdc2 complexes at the G2/M transition of their cell cycle. Although canonical tyrosine kinases are absent in the genome of trypanosomatids, phosphorylation on protein tyrosine residues has been reported in Trypanosoma brucei. Here, we characterized a Wee1-like protein kinase gene from T. brucei. Expression of TbWee1 in a Schizosaccharomyces pombe strain null for Wee1 inhibited cell division and caused cell elongation. This demonstrates the lengthening of G2, which provided cells with extra time to grow before dividing. The Wee1-like protein kinase was expressed in the procyclic and bloodstream proliferative slender forms of T. brucei and the role of Wee1 in cell cycle progression was analyzed by generating RNA interference cell lines. In the procyclic form of T. brucei, the knock-down of TbWee1 expression by RNAi led to inhibition of parasite growth. Abnormal phenotypes showing an increase in the percentage of cells with 1N0K, 0N1K and 2N1K were observed in these RNAi cell lines. Using parasites with a synchronized cell cycle, we demonstrated that TbWee1 is linked to the G2/M phase. We also showed that TbWee1 is an essential gene necessary for proper cell cycle progression and parasite growth in T. brucei. Our results provide evidence for the existence of a functional Wee1 in T. brucei with a potential role in cell division at G2/M.

  3. Sleep Medicine Textbook

    OpenAIRE

    Bassetti, Claudio; Dogas, Zoran; Peigneux, Philippe

    2014-01-01

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

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

    OpenAIRE

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

    2010-01-01

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

  5. Sleep Disorders (PDQ)

    Science.gov (United States)

    ... Professionals Questions to Ask about Your Treatment Research Sleep Disorders (PDQ®)–Patient Version General Information About Sleep Disorders Go to Health Professional Version Key Points Getting ...

  6. Sleep and sleep disorders in older adults.

    Science.gov (United States)

    Crowley, Kate

    2011-03-01

    A common but significant change associated with aging is a profound disruption to the daily sleep-wake cycle. It has been estimated that as many as 50% of older adults complain about difficulty initiating or maintaining sleep. Poor sleep results in increased risk of significant morbidity and mortality. Moreover, in younger adults, compromised sleep has been shown to have a consistent effect on cognitive function, which may suggest that sleep problems contribute to the cognitive changes that accompany older age. The multifactorial nature of variables affecting sleep in old age cannot be overstated. Changes in sleep have been thought to reflect normal developmental processes, which can be further compromised by sleep disturbances secondary to medical or psychiatric diseases (e.g., chronic pain, dementia, depression), a primary sleep disorder that can itself be age-related (e.g., Sleep Disordered Breathing and Periodic Limb Movements During Sleep), or some combination of any of these factors. Given that changes in sleep quality and quantity in later life have implications for quality of life and level of functioning, it is imperative to distinguish the normal age-related sleep changes from those originating from pathological processes. PMID:21225347

  7. 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.

  8. Sleep physiology and sleep disorders in childhood

    Directory of Open Access Journals (Sweden)

    El Shakankiry HM

    2011-09-01

    Full Text Available Hanan M El ShakankiryKing Fahd University Hospital, Al Dammam University, Al Khobar, Kingdom of Saudi ArabiaAbstract: Sleep has long been considered as a passive phenomenon, but it is now clear that it is a period of intense brain activity involving higher cortical functions. Overall, sleep affects every aspect of a child's development, particularly higher cognitive functions. Sleep concerns are ranked as the fifth leading concern of parents. Close to one third of all children suffer from sleep disorders, the prevalence of which is increased in certain pediatric populations, such as children with special needs, children with psychiatric or medical diagnoses and children with autism or pervasive developmental disorders. The paper reviews sleep physiology and the impact, classification, and management of sleep disorders in the pediatric age group.Keywords: sleep physiology, sleep disorders, childhood, epilepsy

  9. 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.

  10. 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.

  11. Trypanosoma brucei Infection in asymptomatic greater Kudus (Tragelaphus strepsiceros) on a game ranch in Zambia.

    Science.gov (United States)

    Munang'andu, Hetron Mweemba; Siamudaala, Victor; Munyeme, Musso; Nambota, Andrew; Mutoloki, Stephen; Matandiko, Wigganson

    2010-03-01

    Trypomastogotes of Trypanosoma brucei were detected from 4 asymptomatic kudus (Tragelaphus strepsiceros) on a game ranch located approximately 45 km north east of Lusaka, Zambia. Blood smears examined from 14 wildlife species comprising of the impala (Aepyceros melampus), Kafue lechwe (kobus leche kafuensis), sable antelope (Hippotragus niger), tsessebe (Damaliscus lunatus), warthog (Phacochoerus aethiopicus), puku (Kobus vardoni), zebra (Equus burchelli), waterbuck (Kobus ellipsiprymnus), bushbuck (Tragelaphus scriptus), reedbuck (Redunca arundinum), wilderbeest (Connochaetes taurinus), hartebeest (Alcephelus lichtensteini), African buffalo (Syncerus caffer), and kudu (Tragelaphus strepsiceros) showed that only the kudu had T. brucei. Although game ranching has emerged to be a successful ex-situ conservation strategy aimed at saving the declining wildlife population in the National Parks, our findings suggest that it has the potential of aiding the re-distribution of animal diseases. Hence, there is a need for augmenting wildlife conservation with disease control strategies aimed at reducing the risk of disease transmission between wildlife and domestic animals. PMID:20333288

  12. 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.

  13. Metabolic consequences of sleep and sleep loss

    OpenAIRE

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

    2008-01-01

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

  14. Sleep apnea and sleep : diagnostic aspects

    OpenAIRE

    Sahlin, Carin

    2009-01-01

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

  15. 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

  16. Identification of Paralogous Life-Cycle Stage Specific Cytoskeletal Proteins in the Parasite Trypanosoma brucei

    OpenAIRE

    Neil Portman; Keith Gull

    2014-01-01

    The life cycle of the African trypanosome Trypanosoma brucei, is characterised by a transition between insect and mammalian hosts representing very different environments that present the parasite with very different challenges. These challenges are met by the expression of life-cycle stage-specific cohorts of proteins, which function in systems such as metabolism and immune evasion. These life-cycle transitions are also accompanied by morphological rearrangements orchestrated by microtubule ...

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

    OpenAIRE

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

    1990-01-01

    The variant-specific surface glycoprotein (VSG) gene 221 of Trypanosoma brucei is transcribed as part of a 60 kb expression site (ES). We have identified the promoter controlling this multigene transcription unit by the use of 221 chromosome-enriched DNA libraries and VSG gene 221 expression site specific transcripts. The start of transcription was determined by hybridization and RNase protection analysis of nascent RNA. The 5' ends of the major transcripts coming from the initiation region m...

  18. Reconstitution of a surface transferrin binding complex in insect form Trypanosoma brucei.

    OpenAIRE

    Ligtenberg, M.J.; Bitter, W.; Kieft, R.; Steverding, D; Janssen, H.; Calafat, J.; Borst, P

    1994-01-01

    In the bloodstream of the mammalian host, Trypanosoma brucei takes up host transferrin by means of a high-affinity uptake system, presumably a transferrin receptor. Transferrin-binding activity is seen in the flagellar pocket and is absent in insect form trypanosomes. By transfection we have reconstituted a transferrin-binding complex in insect form trypanosomes. Formation of this complex requires the products of two genes that are part of a variant surface glycoprotein expression site, expre...

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

    OpenAIRE

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

    2002-01-01

    Genetic analysis of Trypanosoma spp. depends on the detection of variation between strains. We have used the amplified fragment length polymorphism (AFLP) technique to develop a convenient and reliable method for genetic characterization of Trypanosome (sub)species. AFLP accesses multiple independent sites within the genome and would allow a better definition of the relatedness of different Trypanosome (sub)species. Nine isolates (3 from each T. brucei subspecies) were tested with 40 AFLP pri...

  20. Genetic validation of aminoacyl-tRNA synthetases as drug targets in Trypanosoma brucei.

    Science.gov (United States)

    Kalidas, Savitha; Cestari, Igor; Monnerat, Severine; Li, Qiong; Regmi, Sandesh; Hasle, Nicholas; Labaied, Mehdi; Parsons, Marilyn; Stuart, Kenneth; Phillips, Margaret A

    2014-04-01

    Human African trypanosomiasis (HAT) is an important public health threat in sub-Saharan Africa. Current drugs are unsatisfactory, and new drugs are being sought. Few validated enzyme targets are available to support drug discovery efforts, so our goal was to obtain essentiality data on genes with proven utility as drug targets. Aminoacyl-tRNA synthetases (aaRSs) are known drug targets for bacterial and fungal pathogens and are required for protein synthesis. Here we survey the essentiality of eight Trypanosoma brucei aaRSs by RNA interference (RNAi) gene expression knockdown, covering an enzyme from each major aaRS class: valyl-tRNA synthetase (ValRS) (class Ia), tryptophanyl-tRNA synthetase (TrpRS-1) (class Ib), arginyl-tRNA synthetase (ArgRS) (class Ic), glutamyl-tRNA synthetase (GluRS) (class 1c), threonyl-tRNA synthetase (ThrRS) (class IIa), asparaginyl-tRNA synthetase (AsnRS) (class IIb), and phenylalanyl-tRNA synthetase (α and β) (PheRS) (class IIc). Knockdown of mRNA encoding these enzymes in T. brucei mammalian stage parasites showed that all were essential for parasite growth and survival in vitro. The reduced expression resulted in growth, morphological, cell cycle, and DNA content abnormalities. ThrRS was characterized in greater detail, showing that the purified recombinant enzyme displayed ThrRS activity and that the protein localized to both the cytosol and mitochondrion. Borrelidin, a known inhibitor of ThrRS, was an inhibitor of T. brucei ThrRS and showed antitrypanosomal activity. The data show that aaRSs are essential for T. brucei survival and are likely to be excellent targets for drug discovery efforts. PMID:24562907

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

    Science.gov (United States)

    de Macêdo, Juan P; Schumann Burkard, Gabriela; Niemann, Moritz; Barrett, Michael P; Vial, Henri; Mäser, Pascal; Roditi, Isabel; Schneider, André; Bütikofer, Peter

    2015-05-01

    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 action or targeting. PMID

  2. 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.

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

    OpenAIRE

    Michael Wink; Vera Rosenkranz

    2008-01-01

    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, c...

  4. 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

  5. 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…

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

    Directory of Open Access Journals (Sweden)

    Ziyin Li

    2008-04-01

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

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

    Science.gov (United States)

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

    2003-04-11

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

  8. 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.

  9. 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.

  10. 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.

  11. 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…

  12. 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.

  13. 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. PMID:1621022

  14. 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.

  15. Sleep disorders in children

    OpenAIRE

    2007-01-01

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

  16. 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...

  17. Ostriches sleep like platypuses.

    Directory of Open Access Journals (Sweden)

    John A Lesku

    Full Text Available Mammals and birds engage in two distinct states of sleep, slow wave sleep (SWS and rapid eye movement (REM sleep. SWS is characterized by slow, high amplitude brain waves, while REM sleep is characterized by fast, low amplitude waves, known as activation, occurring with rapid eye movements and reduced muscle tone. However, monotremes (platypuses and echidnas, the most basal (or 'ancient' group of living mammals, show only a single sleep state that combines elements of SWS and REM sleep, suggesting that these states became temporally segregated in the common ancestor to marsupial and eutherian mammals. Whether sleep in basal birds resembles that of monotremes or other mammals and birds is unknown. Here, we provide the first description of brain activity during sleep in ostriches (Struthio camelus, a member of the most basal group of living birds. We found that the brain activity of sleeping ostriches is unique. Episodes of REM sleep were delineated by rapid eye movements, reduced muscle tone, and head movements, similar to those observed in other birds and mammals engaged in REM sleep; however, during REM sleep in ostriches, forebrain activity would flip between REM sleep-like activation and SWS-like slow waves, the latter reminiscent of sleep in the platypus. Moreover, the amount of REM sleep in ostriches is greater than in any other bird, just as in platypuses, which have more REM sleep than other mammals. These findings reveal a recurring sequence of steps in the evolution of sleep in which SWS and REM sleep arose from a single heterogeneous state that became temporally segregated into two distinct states. This common trajectory suggests that forebrain activation during REM sleep is an evolutionarily new feature, presumably involved in performing new sleep functions not found in more basal animals.

  18. Sleep locally, act globally.

    Science.gov (United States)

    Rattenborg, Niels C; Lima, Steven L; Lesku, John A

    2012-10-01

    In most animals, sleep is considered a global brain and behavioral state. However, recent intracortical recordings have shown that aspects of non-rapid eye movement (NREM) sleep and wakefulness can occur simultaneously in different parts of the cortex in mammals, including humans. Paradoxically, however, NREM sleep still manifests as a global behavioral shutdown. In this review, the authors examine this paradox from an evolutionary perspective. On the basis of strategic modeling, they suggest that in animals with brains composed of heavily interconnected and functionally interdependent units, a global regulator of sleep maintains the behavioral shutdown that defines sleep and thereby ensures that local use-dependent functions are performed in a safe and efficient manner. This novel perspective has implications for understanding deficits in human cognitive performance resulting from sleep deprivation, sleep disorders such as sleepwalking, changes in consciousness that occur during sleep, and the function of sleep itself. PMID:22572533

  19. Patterns of sleep behaviour.

    Science.gov (United States)

    Webb, W. B.

    1972-01-01

    Discussion of the electroencephalogram as the critical measurement procedure for sleep research, and survey of major findings that have emerged in the last decade on the presence of sleep within the twenty-four-hour cycle. Specifically, intrasleep processes, frequency of stage changes, sequence of stage events, sleep stage amounts, temporal patterns of sleep, and stability of intrasleep pattern in both man and lower animals are reviewed, along with some circadian aspects of sleep, temporal factors, and number of sleep episodes. It is felt that it is particularly critical to take the presence of sleep into account whenever performance is considered. When it is recognized that responsive performance is extremely limited during sleep, it is easy to visualize the extent to which performance is controlled by sleep itself.

  20. 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- ...

  1. All about Sleep (For Parents)

    Science.gov (United States)

    ... Kids For Parents MORE ON THIS TOPIC Naps Sleepwalking Nightmares Night Terrors Sleep and Your 1- to ... Sleep Apnea Sleep Problems in Teens Separation Anxiety Sleepwalking Nightmares What Kids Say About: Sleep Time for ...

  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. Sleep disorders in the elderly

    Science.gov (United States)

    ... as reading or listening to music. Avoid using sleeping pills to help you sleep, if possible. They can ... taking sleep medications. If you think you need sleeping pills, talk with your doctor about which pills are ...

  4. 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' ...

  5. [Sleep and dreams in pictures].

    Science.gov (United States)

    Stoll, R T

    1995-04-11

    Human life is divided into two thirds wakefulness and one third sleep. A newborn child sleeps to strengthen, the adult for regeneration. At the end of life man sinks down into the sleep of death: Hypnos and Thanatos are twin sons of the Queen of Night. Myths from different cultures are influenced by the experience of sleep and its inner world of pictures, the dreams. Artists, painters and sculptors let their visions float steadily into new pictures, and creatures of sleep formed out of diverse materials. Devine sleep, sleep for new life, sleep of health, creative sleep, prophetic sleep, sleep for revelation and for decisions. PMID:7732243

  6. 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).

  7. Biochemical Regulation of Sleep and Sleep Biomarkers

    OpenAIRE

    Clinton, James M.; Davis, Christopher J.; Zielinski, Mark R.; Jewett, Kathryn A.; Krueger, James M.

    2011-01-01

    Symptoms commonly associated with sleep loss and chronic inflammation include sleepiness, fatigue, poor cognition, enhanced sensitivity to pain and kindling stimuli, excess sleep and increases in circulating levels of tumor necrosis factor α (TNF) in humans and brain levels of interleukin-1 β (IL1) and TNF in animals. Cytokines including IL1 and TNF partake in non-rapid eye movement sleep (NREMS) regulation under physiological and inflammatory conditions. Administration of exogenous IL1 or TN...

  8. Sleep physiology and sleep disorders in childhood

    OpenAIRE

    El Shakankiry HM

    2011-01-01

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

  9. Ethanolamine phosphoglycerol attachment to eEF1A is not essential for normal growth of Trypanosoma brucei

    OpenAIRE

    Eva Greganova; Peter Bütikofer

    2012-01-01

    Eukaryotic elongation factor 1A (eEF1A) is the only protein modified by ethanolamine phosphoglycerol (EPG). In mammals and plants, EPG is attached to conserved glutamate residues located in eEF1A domains II and III, whereas in the unicellular eukaryote, Trypanosoma brucei, a single EPG moiety is attached to domain III. A biosynthetic precursor of EPG and structural requirements for EPG attachment to T. brucei eEF1A have been reported, but the role of this unique protein modification in cellul...

  10. 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.

  11. A mixed methods study of a health worker training intervention to increase syndromic referral for gambiense human African trypanosomiasis in South Sudan.

    Directory of Open Access Journals (Sweden)

    Jennifer J Palmer

    2014-03-01

    Full Text Available BACKGROUND: Active screening by mobile teams is considered the most effective method for detecting gambiense-type human African trypanosomiasis (HAT but constrained funding in many post-conflict countries limits this approach. Non-specialist health care workers (HCWs in peripheral health facilities could be trained to identify potential cases for testing based on symptoms. We tested a training intervention for HCWs in peripheral facilities in Nimule, South Sudan to increase knowledge of HAT symptomatology and the rate of syndromic referrals to a central screening and treatment centre. METHODOLOGY/PRINCIPAL FINDINGS: We trained 108 HCWs from 61/74 of the public, private and military peripheral health facilities in the county during six one-day workshops and assessed behaviour change using quantitative and qualitative methods. In four months prior to training, only 2/562 people passively screened for HAT were referred from a peripheral HCW (0 cases detected compared to 13/352 (2 cases detected in the four months after, a 6.5-fold increase in the referral rate observed by the hospital. Modest increases in absolute referrals received, however, concealed higher levels of referral activity in the periphery. HCWs in 71.4% of facilities followed-up had made referrals, incorporating new and pre-existing ideas about HAT case detection into referral practice. HCW knowledge scores of HAT symptoms improved across all demographic sub-groups. Of 71 HAT referrals made, two-thirds were from new referrers. Only 11 patients completed the referral, largely because of difficulties patients in remote areas faced accessing transportation. CONCLUSIONS/SIGNIFICANCE: The training increased knowledge and this led to more widespread appropriate HAT referrals from a low base. Many referrals were not completed, however. Increasing access to screening and/or diagnostic tests in the periphery will be needed for greater impact on case-detection in this context. These data

  12. Trypanosoma brucei modifies the tsetse salivary composition, altering the fly feeding behavior that favors parasite transmission.

    Directory of Open Access Journals (Sweden)

    Jan Van Den Abbeele

    Full Text Available Tsetse flies are the notorious transmitters of African trypanosomiasis, a disease caused by the Trypanosoma parasite that affects humans and livestock on the African continent. Metacyclic infection rates in natural tsetse populations with Trypanosoma brucei, including the two human-pathogenic subspecies, are very low, even in epidemic situations. Therefore, the infected fly/host contact frequency is a key determinant of the transmission dynamics. As an obligate blood feeder, tsetse flies rely on their complex salivary potion to inhibit host haemostatic reactions ensuring an efficient feeding. The results of this experimental study suggest that the parasite might promote its transmission through manipulation of the tsetse feeding behavior by modifying the saliva composition. Indeed, salivary gland Trypanosoma brucei-infected flies display a significantly prolonged feeding time, thereby enhancing the likelihood of infecting multiple hosts during the process of a single blood meal cycle. Comparison of the two major anti-haemostatic activities i.e. anti-platelet aggregation and anti-coagulation activity in these flies versus non-infected tsetse flies demonstrates a significant suppression of these activities as a result of the trypanosome-infection status. This effect was mainly related to the parasite-induced reduction in salivary gland gene transcription, resulting in a strong decrease in protein content and related biological activities. Additionally, the anti-thrombin activity and inhibition of thrombin-induced coagulation was even more severely hampered as a result of the trypanosome infection. Indeed, while naive tsetse saliva strongly inhibited human thrombin activity and thrombin-induced blood coagulation, saliva from T. brucei-infected flies showed a significantly enhanced thrombinase activity resulting in a far less potent anti-coagulation activity. These data clearly provide evidence for a trypanosome-mediated modification of the tsetse

  13. A Gateway® compatible vector for gene silencing in bloodstream form Trypanosoma brucei

    OpenAIRE

    Kalidas, Savitha; Li, Qiong; Margaret A Phillips

    2011-01-01

    RNA interference is the most rapid method for generation of conditional knockdown mutants in Trypanosoma brucei. The dual T7 promoter (pZJM) and the stem-loop vectors have been widely used to generate stable inducible RNAi cell lines with the latter providing tighter regulatory control. However, the steps for cloning stem-loop constructs are cumbersome requiring either multiple cloning steps or multi-fragment ligation reactions. We report the development of a vector (pTrypRNAiGate) derived fr...

  14. Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective Trypanosoma brucei Inhibitors.

    Science.gov (United States)

    Florence, Gordon J; Fraser, Andrew L; Gould, Eoin R; King, Elizabeth F; Menzies, Stefanie K; Morris, Joanne C; Thomson, Marie I; Tulloch, Lindsay B; Zacharova, Marija K; Smith, Terry K

    2016-07-19

    Neglected tropical diseases caused by parasitic infections are an ongoing and increasing concern. They are a burden to human and animal health, having the most devastating effect on the world's poorest countries. Building upon our previously reported triazole analogues, in this study we describe the synthesis and biological testing of other novel heterocyclic acetogenin-inspired derivatives, namely 3,5-isoxazoles, furoxans, and furazans. Several of these compounds maintain low-micromolar levels of inhibition against Trypanosoma brucei, whilst having no observable inhibitory effect on mammalian cells, leading to the possibility of novel lead compounds for selective treatment. PMID:27283448

  15. Evidence for a degradosome-like complex in the mitochondria of Trypanosoma brucei

    OpenAIRE

    Mattiacio, Jonelle L.; Read, Laurie K.

    2009-01-01

    Mitochondrial RNA turnover in yeast involves the degradosome, composed of DSS-1 exoribonuclease and SUV3 RNA helicase. Here, we describe a degradosome-like complex, containing SUV3 and DSS-1 homologues, in the early branching protozoan, Trypanosoma brucei. TbSUV3 is mitochondrially localized and co-sediments with TbDSS-1 on glycerol gradients. Co-immunoprecipitation demonstrates that TbSUV3 and TbDSS-1 associate in a stable complex, which differs from the yeast degradosome in that it is not s...

  16. Sleep Eduction: Treatment & Therapy

    Science.gov (United States)

    ... Facts Causes and Risk Factors Diagnosis and Treatment Sleepwalking Overview & Facts Symptoms & Risk Factors Diagnosis & Treatment Sleep Terrors Overview & Facts Symptoms & Risk Factors Diagnosis & Treatment Sleep Eating Disorder Overview & Facts Symptoms & Risk Factors Diagnosis & Treatment REM ...

  17. Teenagers and sleep

    Science.gov (United States)

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

  18. Brain Basics: Understanding Sleep

    Science.gov (United States)

    ... up. Some children experience bedwetting, night terrors, or sleepwalking during deep sleep. When we switch into REM ... stimulate some parts of the brain and can cause insomnia, or an inability to sleep. Many antidepressants ...

  19. Metformin and sleep disorders

    OpenAIRE

    Somsri Wiwanitkit; Viroj Wiwanitkit

    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.

  20. Sleep and Aging: Insomnia

    Science.gov (United States)

    ... page please turn Javascript on. Sleep and Aging Insomnia Insomnia is the most common sleep complaint at ... at greater risk for falling. Health Issues and Insomnia Disorders that cause pain or discomfort during the ...

  1. 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. PMID:27553980

  2. 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...... duration and single measures of salivary cortisol at awakening, which was observed in 3 studies. In these studies, sleep duration was also associated with low evening cortisol levels, steep diurnal deviation of cortisol and/or high area under the curve. Together these findings suggest that longer sleep...

  3. 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

    2010-01-01

    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 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: R2 = .38; Americans: R2 = .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. PMID:15251909

  4. Pediatric Sleep Surgery

    Directory of Open Access Journals (Sweden)

    Cecille Gail Sulman

    2014-06-01

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

  5. Pediatric Sleep Surgery

    OpenAIRE

    Cecille Gail Sulman

    2014-01-01

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

  6. Sleep disorders and stroke

    OpenAIRE

    Wallace, Douglas M; Ramos, Alberto R.; Rundek, Tatjana

    2012-01-01

    The purpose of this review is to highlight existing literature on the epidemiology, pathophysiology, and treatments of stroke sleep disorders. Stroke sleep disorders are associated with many intermediary vascular risk factors leading to stroke, but they may also influence these risk factors through direct or indirect mechanisms. Sleep disturbances may be further exacerbated by stroke or caused by stroke. Unrecognized and untreated sleep disorders may influence rehabilitation efforts and poor ...

  7. 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.

  8. 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.

  9. Sleep and Your Preschooler

    Science.gov (United States)

    ... Story" 5 Things to Know About Zika & Pregnancy Sleep and Your Preschooler KidsHealth > For Parents > Sleep and Your Preschooler Print A A A Text ... Preschoolers need about 11 to 12 hours of sleep each day, which can include a nap. There's ...

  10. Is Sleep Essential?

    OpenAIRE

    Chiara Cirelli; Giulio Tononi

    2008-01-01

    No current hypothesis can explain why animals need to sleep. Yet, sleep is universal, tightly regulated, and cannot be deprived without deleterious consequences. This suggests that searching for a core function of sleep, particularly at the cellular level, is still a worthwhile exercise.

  11. PILL series. Recognising sleep apnoea

    OpenAIRE

    How, Choon How; Hsu, Pon Poh; Tan, Kah Leong Alvin

    2015-01-01

    Most people spend a third of their lives sleeping, and thus, sleep has a major impact on all of us. As sleep is a function and not a structure, it is challenging to treat and prevent its complications. Sleep apnoea is one such complication, with serious and potentially life-threatening consequences. Local studies estimate that about 15% of Singapore’s population is afflicted with sleep apnoea. The resulting sleep fragmentation may result in poor quality of sleep, leading to daytime sleepiness...

  12. 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.

  13. 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.

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

    NARCIS (Netherlands)

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

    1980-01-01

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

  15. 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.

  16. 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

  17. 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.

  18. Sleep apnea and stroke.

    Science.gov (United States)

    Culebras, Antonio

    2015-01-01

    Clinical evidence has established that sleep apnea is a risk factor for stroke. Patients with stroke have a high prevalence of sleep apnea that may have preceded or developed as a result of the stroke. Well-established concurrent stroke risk factors for stroke like hypertension and atrial fibrillation respond favorably to the successful treatment of sleep apnea. The gold standard diagnosis of sleep apnea is obtained in the sleep laboratory, but unattended polysomnography is gaining acceptance. Positive airway pressure (PAP) (continuous positive airway pressure [CPAP] or bilevel positive airway pressure [BiPAP]) applications are the gold-standard treatment of sleep apnea. Suggestive evidence indicates that stroke occurrence or recurrence may be reduced with treatment of sleep apnea. PMID:25407131

  19. Dietary Macronutrients and Sleep.

    Science.gov (United States)

    Lindseth, Glenda; Murray, Ashley

    2016-08-01

    This study examined the effects of macronutrient diets on sleep quantity and quality. Using a repeated-measures, randomized crossover study design, 36 young adults served as their own control, and consumed high protein, carbohydrate, fat, and control diets. Treatment orders were counterbalanced across the dietary groups. Following consumption of the study diets, sleep measures were examined for within-subject differences. Fatty acid intakes and serum lipids were further analyzed for differences. Sleep actigraphs indicated wake times and wake minutes (after sleep onset) were significantly different when comparing consumption of macronutrient diets and a control diet. Post hoc testing indicated high carbohydrate intakes were associated with significantly shorter (p Sleep Quality Index© post hoc results indicated high fat intake was associated with significantly better (p sleep in comparison with the other diets. These results highlight the effects that dietary manipulations may have on sleep. PMID:27170039

  20. 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…

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

    Science.gov (United States)

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

    2009-01-01

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

  2. Sleep 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.

  3. 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. PMID:21977062

  4. Chronic sleep reduction in adolescents

    OpenAIRE

    Dewald-Kaufmann, J.F.

    2012-01-01

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

  5. 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

  6. 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. PMID:26478197

  7. 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.

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

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    OpenAIRE

    LeBourgeois, Monique K.; Giannotti, Flavia; CORTESI, FLAVIA; Wolfson, Amy; Harsh, John

    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...

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

    OpenAIRE

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

    2010-01-01

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

  11. Sleep-Route: Routing through Sleeping Sensors

    OpenAIRE

    Sarkar, Chayan; Rao, Vijay S.; Prasad, R. Venkatesha

    2014-01-01

    In this article, we propose an energy-efficient data gathering scheme for wireless sensor network called Sleep-Route, which splits the sensor nodes into two sets - active and dormant (low-power sleep). Only the active set of sensor nodes participate in data collection. The sensing values of the dormant sensor nodes are predicted with the help of an active sensor node. Virtual Sensing Framework (VSF) provides the mechanism to predict the sensing values by exploiting the data correlation among ...

  12. 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 (

  13. Irregular sleep-wake syndrome

    Science.gov (United States)

    Sleep-wake syndrome - irregular ... routine during the day. The amount of total sleep time is normal, but the body clock loses ... have a different condition, such as shift work sleep disorder or jet lag syndrome.

  14. American Academy of Sleep Medicine

    Science.gov (United States)

    ... help you share AASM sleep duration recommendations Senate Finance Committee considers revisions to Stark Law These papers ... announcement: After 38 years of jointly publishing the journal SLEEP with the Sleep Research Society, the AASM ...

  15. Sleep and metabolic function

    OpenAIRE

    Morselli, Lisa L.; Guyon, Aurore; Spiegel, Karine

    2011-01-01

    Evidence for the role of sleep on metabolic and endocrine function has been reported more than four decades ago. In the past 30 years, the prevalence of obesity and diabetes has greatly increased in industrialized countries, and self-imposed sleep curtailment, now very common, is starting to be recognized as a contributing factor, alongside with increased caloric intake and decreased physical activity. Furthermore, obstructive sleep apnea, a chronic condition characterized by recurrent upper ...

  16. DELIRIUM: IS SLEEP IMPORTANT?

    OpenAIRE

    Watson, Paula L.; Ceriana, Piero; Fanfulla, Francesco

    2012-01-01

    Delirium and poor sleep quality are common and often co-exist in hospitalized patients. A link between these disorders has been hypothesized but whether this link is a cause and effect relationship or simply an association resulting from shared mechanisms is yet to be determined. Potential shared mechanisms include: abnormalities of neurotransmitters, tissue ischemia, inflammation, and sedative exposure. Sedatives, while decreasing sleep latency, often cause a decrease in slow wave sleep and ...

  17. Classification of Sleep Disorders

    OpenAIRE

    Michael J. Thorpy

    2012-01-01

    The classification of sleep disorders is necessary to discriminate between disorders and to facilitate an understanding of symptoms, etiology, and pathophysiology that allows for appropriate treatment. The earliest classification systems, largely organized according to major symptoms (insomnia, excessive sleepiness, and abnormal events that occur during sleep), were unable to be based on pathophysiology because the cause of most sleep disorders was unknown. These 3 symptom-based categories ar...

  18. Sleep enhances exposure therapy

    OpenAIRE

    Kleim, Birgit; Wilhelm, F. H.; Temp, L; Margraf, J.; Wiederhold, B. K.; Rasch, Björn

    2014-01-01

    Background: Sleep benefits memory consolidation. Here, we tested the beneficial effect of sleep on memory consolidation following exposure psychotherapy of phobic anxiety. Method: A total of 40 individuals afflicted with spider phobia according to DSM-IV underwent a one-session virtual reality exposure treatment and either slept for 90 min or stayed awake afterwards. Results: Sleep following exposure therapy compared with wakefulness led to better reductions in self-reported fear (p = 0...

  19. Adenosine and Sleep

    OpenAIRE

    Bjorness, Theresa E.; Greene, Robert W.

    2009-01-01

    Over the last several decades the idea that adenosine (Ado) plays a role in sleep control was postulated due in large part to pharmacological studies that showed the ability of Ado agonists to induce sleep and Ado antagonists to decrease sleep. A second wave of research involving in vitro cellular analytic approaches and subsequently, the use of neurochemical tools such as microdialysis, identified a population of cells within the brainstem and basal forebrain arousal centers, with activity t...

  20. Pathophysiology of Sleep Apnea

    OpenAIRE

    Dempsey, Jerome A; Veasey, Sigrid C.; Morgan, Barbara J.; O'Donnell, Christopher P.

    2010-01-01

    Sleep-induced apnea and disordered breathing refers to intermittent, cyclical cessations or reductions of airflow, with or without obstructions of the upper airway (OSA). In the presence of an anatomically compromised, collapsible airway, the sleep-induced loss of compensatory tonic input to the upper airway dilator muscle motor neurons leads to collapse of the pharyngeal airway. In turn, the ability of the sleeping subject to compensate for this airway obstruction will determine the degree o...

  1. Sleep apnoea in acromegaly.

    OpenAIRE

    Perks, W H; Horrocks, P M; Cooper, R A; Bradbury, S; Allen, A; Baldock, N; Prowse, K.; Van't Hoff, W

    1980-01-01

    Day time somnolence or excessive snoring, or both, occurred in five out of 11 patients with acromegaly. All five had episodes of sleep apnoea, and three had the sleep apnoea syndrome. Growth hormone concentrations were higher (p less than 0.025) in these patients than in the six patients without these symptoms. One patient with daytime somnolence and one asymptomatic patient had flow loop evidence of upper airways obstruction. Two of the patients with the sleep apnoea syndrome had cardiomegal...

  2. Sleep and Hypertension

    OpenAIRE

    Calhoun, David A.; Harding, Susan M.

    2010-01-01

    Ambulatory BP studies indicate that even small increases in BP, particularly nighttime BP levels, are associated with significant increases in cardiovascular morbidity and mortality. Accordingly, sleep-related diseases that induce increases in BP would be anticipated to substantially affect cardiovascular risk. Both sleep deprivation and insomnia have been linked to increases in incidence and prevalence of hypertension. Likewise, sleep disruption attributable to restless legs syndrome increas...

  3. Isolated sleep paralysis

    OpenAIRE

    Sawant, Neena S.; Shubhangi R Parkar; 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.

  4. The Function of Sleep

    OpenAIRE

    Daniel A. Barone; Krieger, Ana C.

    2015-01-01

    The importance of sleep can be ascertained by noting the effects of its loss, which tends to be chronic and partial, on cognition, mood, alertness, and overall health. Many theories have been put forth to explain the function of sleep in humans, including proposals based on energy conservation, ecological adaptations, neurocognitive function, neural plasticity, nervous system and physical health, and performance. Most account for only a portion of sleep behavior and few are based on strong ex...

  5. 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 ...

  6. Burnout and sleep

    OpenAIRE

    Ekstedt, Mirjam

    2005-01-01

    Burnout and Sleep The overall aim of this thesis was to describe the physiological characteristics of sleep in persons with burnout and the relation between sleep and a number of physiological stress markers. The aim was also to evaluate the diurnal pattern of subjective sleepiness and fatigue across workday and weekend, and to describe the experiences of time preceding burnout from a life world perspective. This thesis focuses on burnout in white-collar workers; one gro...

  7. 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.

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

    Science.gov (United States)

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

    2016-01-14

    Intercellular communication between parasites and with host cells provides mechanisms for parasite development, immune evasion, and disease pathology. Bloodstream African trypanosomes produce membranous nanotubes that originate from the flagellar membrane and disassociate into free extracellular vesicles (EVs). Trypanosome EVs contain several flagellar proteins that contribute to virulence, and Trypanosoma brucei rhodesiense EVs contain the serum resistance-associated protein (SRA) necessary for human infectivity. T. b. rhodesiense EVs transfer SRA to non-human infectious trypanosomes, allowing evasion of human innate immunity. Trypanosome EVs can also fuse with mammalian erythrocytes, resulting in rapid erythrocyte clearance and anemia. These data indicate that trypanosome EVs are organelles mediating non-hereditary virulence factor transfer and causing host erythrocyte remodeling, inducing anemia. PMID:26771494

  9. Trypanosoma brucei: Enrichment by UV of intergenic transcripts from the variable surface glycoprotein gene expression site

    International Nuclear Information System (INIS)

    The expression site for the variable surface glycoprotein (VSG) gene AnTat 1.3A of Trypanosoma brucei is 45 kilobases long and encompasses seven expression site-associated genes (ESAGs). After UV irradiation, several large transcripts from the putative promoter region were strongly enriched. We report that one such major transcript starts near the poly(A) addition site of the first gene (ESAG 7), spans the intergenic region, and extends to the poly(A) addition site of the second gene (ESAG 6), thus bypassing the normal 3' splice site of the ESAG 6 mRNA. Since this transcript is spliced, we conclude that UV irradiation does not inhibit splicing but stabilizes unstable processing products. This demonstrates that at least some intergenic regions of the VSG gene expression site are continuously transcribed in accordance with a polycistronic transcription model

  10. 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. PMID:23622294

  11. [Sleep in depression].

    Science.gov (United States)

    Pringuey, D; Darcourt, G

    1990-11-28

    Insomnia is a cardinal symptom of depression, side by side with alterations of mood and slowing down of psychomotor activities. It bears witness to a rupture in the built-in circadian rhythm: architectural changes in sleep betray a biological desynchronization. Insomnia is also a failed attempt at finding a solution to depression. Total deprivation of sleep for one night may damp down the depressive disorders, and so does partial sleep deprivation in the second part of the night during several days. This leads to the conclusion that the waking-sleep system participates in the expression of symptoms of depression or even contributes to the genesis of the disease. PMID:2148377

  12. The Association of Testosterone Levels with Overall Sleep Quality, Sleep Architecture, and Sleep-Disordered Breathing

    OpenAIRE

    Barrett-Connor, Elizabeth; Dam, Thuy-Tien; Stone, Katie; Harrison, Stephanie Litwack; Redline, Susan; Orwoll, Eric

    2008-01-01

    Context: Little is known about the association of low endogenous testosterone levels and abnormal sleep patterns in older men, although pharmacological doses of testosterone are associated with increased severity of sleep apnea and other sleep disturbances.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. Effect of Daytime Exercise on Sleep Eeg and Subjective Sleep

    Science.gov (United States)

    Sasazawa, Y.; Kawada, T.; Kiryu, Y.

    1997-08-01

    This study was designed to assess the effects of daytime physical exercise on the quality of objective and subjective sleep by examining all-night sleep EEGs. The subjects were five male students, aged 19 to 20 years, who were in the habit of performing regular daytime exercise. The sleep polygraphic parameters in this study were sleep stage time as a percentage of total sleep time (%S1, %S2, %S(3+4), %SREM, %MT), time in bed (TIB), sleep time (ST), total sleep time (TST), sleep onset latency (SOL), waking from sleep, sleep efficiency, number of awakenings, number of stage shifts, number of spindles, and percentages of α and δ waves, all of which were determined by an automatic computer analysis system. The OSA questionnaire was used to investigate subjective sleep. The five scales of the OSA used were sleepiness, sleep maintenance, worry, integrated sleep feeling, and sleep initiation. Each sleep parameter was compared in the exercise and the non-exercise groups. Two-way analysis of variance was applied using subject factor and exercise factor. The main effect of the subject was significant in all parameters and the main effect of exercise in %S(3+4), SOL and sleep efficiency, among the objective sleep parameters. The main effects of the subject, except sleepiness, were significant, as was the main effect of exercise on sleep initiation, among the subjective sleep parameters. These findings suggest that daytime exercise shortened sleep latency and prolonged slow-wave sleep, and that the subjects fell asleep more easily on exercise days. There were also significant individual differences in both the objective and subjective sleep parameters.

  19. Sleep disorders in Parkinson's disease.

    Science.gov (United States)

    Thorpy, Michael J

    2004-01-01

    Depression, dementia, and physiologic changes contribute to the high prevalence of sleep disturbances in patients with Parkinson's disease (PD). Antiparkinsonian drugs also play a role in insomnia by increasing daytime sleepiness and affecting motor symptoms and depression. Common types of sleep disturbances in PD patients include nocturnal sleep disruption and excessive daytime sleepiness, restless legs syndrome, rapid eye movement sleep behavior disorder, sleep apnea, sleep walking and sleep talking, nightmares, sleep terrors, and panic attacks. A thorough assessment should include complete medical and psychiatric histories, sleep history, and a 1- to 2-week sleep diary or Epworth Sleepiness Scale evaluation. Polysomnography or actigraphy may also be indicated. Treatment should address underlying factors such as depression or anxiety. Hypnotic therapy for sleep disturbances in PD patients should be approached with care because of the risks of falling, agitation, drowsiness, and hypotension. Behavioral interventions may also be useful. PMID:15259535

  20. Diagnosing Sleep Disorders | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... REM sleep during their naps. What are Sleep Studies? Sleep studies are tests that measure how well you sleep ... a sleep disorder and how severe it is. Sleep studies are important because untreated sleep disorders can raise ...

  1. 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.

  2. 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. PMID:3016533

  3. Catalytic properties, localization, and in vivo role of Px IV, a novel tryparedoxin peroxidase of Trypanosoma brucei.

    Science.gov (United States)

    Liu, Ilon; Bogacz, Marta; Schaffroth, Corinna; Dirdjaja, Natalie; Krauth-Siegel, R Luise

    2016-06-01

    Px IV is a distant relative of the known glutathione peroxidase-type enzymes of African trypanosomes. Immunofluorescence microscopy of bloodstream cells expressing C-terminally Myc6-tagged Px IV revealed a mitochondrial localization. Recombinant Px IV possesses very low activity as glutathione peroxidase but catalyzes the trypanothione/tryparedoxin-dependent reduction of hydrogen peroxide and, even more efficiently, of arachidonic acid hydroperoxide. Neither overexpression in bloodstream cells nor the deletion of both alleles in bloodstream or procyclic parasites affected the in vitro proliferation. Trypanosoma brucei Px IV shares 58% of all residues with TcGPXII. The orthologous enzymes have in common their substrate preference for fatty acid hydroperoxides. However, the T. cruzi protein has been reported to be localized in the endoplasmic reticulum and to be specific for glutathione as reducing agent. Taken together, our data show that Px IV is a low abundant tryparedoxin peroxidase of T. brucei that is not essential, at least under culture conditions. PMID:27262262

  4. 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. PMID:26758201

  5. 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

  6. 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

  7. [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

  8. Shining evolutionary light on human sleep and sleep disorders.

    Science.gov (United States)

    Nunn, Charles L; Samson, David R; Krystal, Andrew D

    2016-01-01

    Sleep is essential to cognitive function and health in humans, yet the ultimate reasons for sleep-i.e. 'why' sleep evolved-remain mysterious. We integrate findings from human sleep studies, the ethnographic record, and the ecology and evolution of mammalian sleep to better understand sleep along the human lineage and in the modern world. Compared to other primates, sleep in great apes has undergone substantial evolutionary change, with all great apes building a sleeping platform or 'nest'. Further evolutionary change characterizes human sleep, with humans having the shortest sleep duration, yet the highest proportion of rapid eye movement sleep among primates. These changes likely reflect that our ancestors experienced fitness benefits from being active for a greater portion of the 24-h cycle than other primates, potentially related to advantages arising from learning, socializing and defending against predators and hostile conspecifics. Perspectives from evolutionary medicine have implications for understanding sleep disorders; we consider these perspectives in the context of insomnia, narcolepsy, seasonal affective disorder, circadian rhythm disorders and sleep apnea. We also identify how human sleep today differs from sleep through most of human evolution, and the implications of these changes for global health and health disparities. More generally, our review highlights the importance of phylogenetic comparisons in understanding human health, including well-known links between sleep, cognitive performance and health in humans. PMID:27470330

  9. Adenosine and sleep

    International Nuclear Information System (INIS)

    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 A1 receptors, 3H-L-PIA binding was measured. The Bmax values for 3H-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 3H-L-PIA binding resulted from REM sleep deprivation and not from stress

  10. 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

  11. 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

  12. What Are Sleep Studies?

    Science.gov (United States)

    ... Events Spokespeople Email Alerts E-Newsletters About NHLBI Organization NHLBI Director Budget, Planning, & Legislative Advisory Committees Contact Us FAQs Home » Health Information for the Public » Health Topics » Sleep Studies Explore Sleep Studies What Are... Types Who Needs ...

  13. 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

  14. 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.

  15. Functional dissection of T. brucei Protein Tyrosine Phosphatase 1 and investigation of its development as a therapeutic target

    OpenAIRE

    Ruberto, Irene

    2011-01-01

    Trypanosoma brucei undergoes developmentally regulated morphological and biochemical changes during its life cycle, being transmitted between the mammalian host and the tsetse fly. It is generally recognized that cellular responses to environmental changes are mediated through signalling pathways, but our understanding of trypanosome signal transduction during differentiation is limited. Protein Tyrosine Phosphatase 1 (TbPTP1) is the one of the few factors identified to b...

  16. A structural domain mediates attachment of ethanolamine phosphoglycerol to eukaryotic elongation factor 1A in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Eva Greganova

    Full Text Available Ethanolamine phosphoglycerol (EPG represents a protein modification that so far has only been found in eukaryotic elongation factor 1A (eEF1A. In mammals and plants, EPG is covalently attached to two conserved glutamate residues located in domains II and III of eEF1A. In contrast, Trypanosoma brucei eEF1A contains a single EPG attached to Glu362 in domain III. The sequence and/or structural requirements for covalent linkage of EPG to eEF1A have not been determined for any organism. Using a combination of biosynthetic labelling of parasites with tritiated ethanolamine and mass spectrometry analyses, we demonstrate that replacement of Glu362 in T. brucei eEF1A by site-directed mutagenesis prevents EPG attachment, whereas single or multiple amino acid substitutions around the attachment site are not critical. In addition, by expressing a series of eEF1A deletion mutants in T. brucei procyclic forms, we demonstrate that a peptide consisting of 80 amino acids of domain III of eEF1A is sufficient for EPG attachment to occur. Furthermore, EPG addition also occurs if domain III of eEF1A is fused to a soluble reporter protein. To our knowledge, this is the first report addressing amino acid sequence, or structure, requirements for EPG modification of eEF1A in any organism. Using T. brucei as a model organism, we show that amino acid substitutions around the modification site are not critical for EPG attachment and that a truncated version of domain III of eEF1A is sufficient to mediate EPG addition.

  17. 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.

  18. High-resolution complex of papain with remnants of a cysteine protease inhibitor derived from Trypanosoma brucei

    OpenAIRE

    Alphey, Magnus S.; Hunter, William N.

    2006-01-01

    Attempts to cocrystallize the cysteine protease papain derived from the latex of Carica papaya with an inhibitor of cysteine proteases (ICP) from Trypanosoma brucei were unsuccessful. However, crystals of papain that diffracted to higher resolution, 1.5 Å, than other crystals of this archetypal cysteine protease were obtained, so the analysis was continued. Surprisingly, the substrate-binding cleft was occupied by two short peptide fragments which have been assigned as remnants of ICP. Compar...

  19. 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.

  20. 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

  1. Shining evolutionary light on human sleep and sleep disorders

    OpenAIRE

    Charles L Nunn; David R. Samson; Krystal, Andrew D.

    2016-01-01

    Sleep is essential to cognitive function and health in humans, yet the ultimate reasons for sleep—i.e. ‘why’ sleep evolved—remain mysterious. We integrate findings from human sleep studies, the ethnographic record, and the ecology and evolution of mammalian sleep to better understand sleep along the human lineage and in the modern world. Compared to other primates, sleep in great apes has undergone substantial evolutionary change, with all great apes building a sleeping platform or ‘nest’. Fu...

  2. 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.

  3. The Function of Sleep

    Directory of Open Access Journals (Sweden)

    Daniel A. Barone

    2015-06-01

    Full Text Available The importance of sleep can be ascertained by noting the effects of its loss, which tends to be chronic and partial, on cognition, mood, alertness, and overall health. Many theories have been put forth to explain the function of sleep in humans, including proposals based on energy conservation, ecological adaptations, neurocognitive function, neural plasticity, nervous system and physical health, and performance. Most account for only a portion of sleep behavior and few are based on strong experimental support. In this review, we present theories proposing why sleep is necessary and supporting data demonstrating the effects of inadequate sleep, with the intention of gleaning further information as to its necessity, which remains one of the most perplexing mysteries in biology.

  4. Sleep effects on breathing and respiratory diseases

    Directory of Open Access Journals (Sweden)

    Choudhary Sumer

    2009-01-01

    Full Text Available To understand normal sleep pattern and physiological changes during sleep, sleep and breathing interaction, nomenclature and scales used in sleep study, discuss the effect of rapid eye movements and non-rapid eye movements while sleep and to review the effects of obstructive and restrictive lung disease on gas exchange during sleep and sleep architecture.

  5. Sleep effects on breathing and respiratory diseases

    OpenAIRE

    Choudhary Sumer; Choudhary Sanjiw

    2009-01-01

    To understand normal sleep pattern and physiological changes during sleep, sleep and breathing interaction, nomenclature and scales used in sleep study, discuss the effect of rapid eye movements and non-rapid eye movements while sleep and to review the effects of obstructive and restrictive lung disease on gas exchange during sleep and sleep architecture.

  6. 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.

  7. Ab initio identification of novel regulatory elements in the genome of Trypanosoma brucei by Bayesian inference on sequence segmentation.

    Directory of Open Access Journals (Sweden)

    Steven Kelly

    Full Text Available BACKGROUND: The rapid increase in the availability of genome information has created considerable demand for both comparative and ab initio predictive bioinformatic analyses. The biology laid bare in the genomes of many organisms is often novel, presenting new challenges for bioinformatic interrogation. A paradigm for this is the collected genomes of the kinetoplastid parasites, a group which includes Trypanosoma brucei the causative agent of human African trypanosomiasis. These genomes, though outwardly simple in organisation and gene content, have historically challenged many theories for gene expression regulation in eukaryotes. METHODOLOGY/PRINCIPLE FINDINGS: Here we utilise a Bayesian approach to identify local changes in nucleotide composition in the genome of T. brucei. We show that there are several elements which are found at the starts and ends of multicopy gene arrays and that there are compositional elements that are common to all intergenic regions. We also show that there is a composition-inversion element that occurs at the position of the trans-splice site. CONCLUSIONS/SIGNIFICANCE: The nature of the elements discovered reinforces the hypothesis that context dependant RNA secondary structure has an important influence on gene expression regulation in Trypanosoma brucei.

  8. Clinical Psychology Training in Sleep and Sleep Disorders

    OpenAIRE

    Meltzer, Lisa J.; Phillips, Cindy; Mindell, Jodi A.

    2009-01-01

    There is growing evidence to suggest that clinical psychologists would benefit from more training in sleep and sleep disorders. Sleep disturbances are commonly comorbid with mental health disorders and this relationship is often bidirectional. In addition, psychologists have become integral members of multidisciplinary sleep medicine teams and there are not enough qualified psychologists to meet the clinical demand. The purpose of this study was to evaluate the current education on sleep and ...

  9. Delayed Sleep Phase Disorder. Prevalence, sleep, circadian rhythm and treatment

    OpenAIRE

    Saxvig, Ingvild West

    2013-01-01

    Adolescence is often characterized by delayed and irregular sleep patterns, with potential negative consequences in terms of school performance and daytime functioning. At the most extreme, a stably delayed sleep phase may reflect a circadian rhythm sleep disorder of the delayed sleep phase type (delayed sleep phase disorder, DSPD). DSPD is assumed to be common amongst adolescents and young adults, but little is known about its prevalence and aetiology, and no guidelines exist ...

  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. Cocaine and Sleep: Early Abstinence

    Directory of Open Access Journals (Sweden)

    Peter T. Morgan

    2007-01-01

    Full Text Available Compulsive cocaine use is associated with a profound dysregulation of sleep. Perhaps the result of chronic use, a significant deterioration in sleep is apparent over the first 3 weeks of abstinence, with no indication of recovery. Interestingly, the diminished sleep is not accompanied by subjective reports of poor or worsening sleep. Rather, subjective reports actually improve over abstinence, while sleep-related cognitive performance declines. A mechanistic understanding of the apparent difference in objective and subjective measures is currently lacking. Here we review the relevant literature on cocaine use and sleep, and discuss the possible relevance of this sleep disturbance in relationship to the underlying disorder and its treatment.

  12. Sleep in traumatic brain injury.

    Science.gov (United States)

    Vermaelen, James; Greiffenstein, Patrick; deBoisblanc, Bennett P

    2015-07-01

    More than one-half million patients are hospitalized annually for traumatic brain injury (TBI). One-quarter demonstrate sleep-disordered breathing, up to 50% experience insomnia, and half have hypersomnia. Sleep disturbances after TBI may result from injury to sleep-regulating brain tissue, nonspecific neurohormonal responses to systemic injury, ICU environmental interference, and medication side effects. A diagnosis of sleep disturbances requires a high index of suspicion and appropriate testing. Treatment starts with a focus on making the ICU environment conducive to normal sleep. Treating sleep-disordered breathing likely has outcome benefits in TBI. The use of sleep promoting sedative-hypnotics and anxiolytics should be judicious. PMID:26118920

  13. 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. PMID:26600106

  14. Sleep disorders in hemodialysis patients

    OpenAIRE

    Sabry Alaa; Abo-Zenah Hamdy; Wafa Ehab; Mahmoud Khaled; El-Dahshan Khaled; Hassan Ahmed; Abbas Tarek; Saleh Abd El-Baset; Okasha Kamal

    2010-01-01

    The prevalence of sleep disorders is higher in patients with kidney failure than the general population. We studied the prevalence of sleep disorders in 88 (mean age; 41.59 ± 16.3 years) chronic hemodialysis (HD) patients at the Urology and Nephrology Center, Mansoura Uni-versity, Egypt over 4-month period. The investigated sleep disorders included insomnia, restless leg syndrome (RLS), obstructive sleep apnea syndrome (OSAS), excessive daytime sleepiness (EDS), narcolepsy and sleep walk...

  15. Genetic factors in sleep disorders.

    OpenAIRE

    Parkes, J. D.; Lock, C B

    1989-01-01

    Several sleep disorders have a genetic basis. These conditions include the narcoleptic syndrome, sleep walking, periodic movements in sleep, circadian delay syndromes and familial insomnia. These disorders illustrate different control mechanisms involved in sleep and wakefulness, including those determining the prevalence and timing of NREM and REM activity, somatomotor inhibition and excitation, autonomic discharge, and the circadian framework of sleep. The genetic defect in narcolepsy has b...

  16. The Neuroprotective Aspects of Sleep

    OpenAIRE

    Eugene, Andy R.; Masiak, Jolanta

    2015-01-01

    Sleep is an important component of human life, yet many people do not understand the relationship between the brain and the process of sleeping. Sleep has been proven to improve memory recall, regulate metabolism, and reduce mental fatigue. A minimum of 7 hours of daily sleep seems to be necessary for proper cognitive and behavioral function. The emotional and mental handicaps associated with chronic sleep loss as well as the highly hazardous situations which can be contributed to the lack of...

  17. 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.

  18. 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.

  19. Management of common sleep disorders.

    Science.gov (United States)

    Ramar, Kannan; Olson, Eric J

    2013-08-15

    Sleep disorders are common and affect sleep quality and quantity, leading to increased morbidity. Patients with sleep disorders can be categorized as those who cannot sleep, those who will not sleep, those with excessive daytime sleepiness, and those with increased movements during sleep. Insomnia, defined as difficulty initiating or maintaining sleep that results in daytime impairment, is diagnosed using history findings and treated with cognitive behavior therapy, with or without sleep hypnotics. Restless legs syndrome is characterized by an urge to move the legs that worsens with rest, is relieved by movement, and often occurs in the evening or at night. Restless legs syndrome is treated based on the frequency of symptoms. Narcolepsy is characterized by excessive sleepiness, cataplexy, hypnagogic or hypnopompic hallucinations, and sleep paralysis. It is diagnosed using a sleep log or actigraphy, followed by overnight polysomnography and a multiple sleep latency test. Narcolepsy is treated with stimulants, such as modafinil; selective serotonin reuptake inhibitors; or gamma hydroxybutyric acid (sodium oxybate). Patients with snoring and witnessed apneas may have obstructive sleep apnea, which is diagnosed using overnight polysomnography. Continuous positive airway pressure is the most common and effective treatment for obstructive sleep apnea. Rapid eye movement sleep behavior disorder is characterized by increased muscle tone during rapid eye movement sleep, resulting in the patient acting out dreams with possible harmful consequences. It is diagnosed based on history and polysomnography findings, and treated with environmental safety measures and melatonin or clonazepam. PMID:23944726

  20. Sleep deprivation in depression

    Directory of Open Access Journals (Sweden)

    Doongaji D

    1979-01-01

    Full Text Available Ten patients diagnosed as suffering from depressive illness were treated with 2 consecutive nights of sleep deprivation. Sleep deprivation was effective in both types of depression viz. endoge-nous and reactive. The improvement was greater and seemed to last longer in endogenous depression as compared to reactive depression at the time of evaluation, 7 days after completion of sleep deprivation. Depressed mood, suicidal tendencies and retard-ation seemed to show the greatest improvement while insight and gastro-intestinal and somatic symptoms, improved the least.

  1. Chimpanzee sleep stages.

    Science.gov (United States)

    Freemon, F. R.; Mcnew, J. J.; Adey, W. R.

    1971-01-01

    The electroencephalogram and electro-oculogram of two unrestrained juvenile chimpanzees was monitored for 7 consecutive nights using telemetry methods. Of the sleeping time, 23% was spent in the rapid eye movement of REM type of sleep, whereas 8, 4, 15, and 10% were spent in non-REM stages 1 through 4, respectively. Seven to nine periods of REM sleep occurred per night. The average time from the beginning of one REM period to the beginning of the next was approximately 85 min.

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    Melisa Gualdron-López

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

  4. 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.

  5. Treatments for Sleep Changes

    Science.gov (United States)

    ... caregivers. Daytime napping and other shifts in the sleep-wake cycle. Individuals may feel very drowsy during the ... problems worse include: Depression Restless legs syndrome, a disorder in which unpleasant “crawling” or “tingling” sensations in ...

  6. Sleep Problems and ADHD

    OpenAIRE

    J Gordon Millichap

    2008-01-01

    The prevalence of sleep problems and their associations with quality of life (QOL), school attendance, and family impacts in children with ADHD were determined in a study at Royal Children's Hospital, University of Melbourne, Australia.

  7. Employees with Sleep Disorders

    Science.gov (United States)

    ... in the legs, described as pins and needles, crawling, and tingling, occur during sleep. As a result ... many more that are not available on the Web site. Contact JAN directly if you have specific ...

  8. Getting Enough Sleep?

    Science.gov (United States)

    ... Illness & disability Drugs, alcohol & smoking Your feelings Relationships Bullying Safety Your future Environmental health Skip section navigation ( ... have around. Sound good? Now consider some possible effects of not getting enough sleep: Feeling angry or ...

  9. Obstructive sleep apnea - adults

    Science.gov (United States)

    ... eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 100. Kimoff RJ. Obstructive sleep ... Textbook of Respiratory Medicine . 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 88. Qaseem A, Holty JE, ...

  10. [Sleep related movement disorders].

    Science.gov (United States)

    Suzuki, Keisuke; Miyamoto, Masayuki; Miyamoto, Tomoyuki; Hirata, Koichi

    2015-06-01

    Sleep related movement disorders (SRMD) are characterized by simple, stereotyped movements occur during sleep, with the exception of restless legs syndrome (RLS). RLS has the following essential features; an urge to move the legs usually accompanied by uncomfortable sensation in the legs, improvement of symptoms after movement (non-stereotypical movements, such as walking and stretching, to reduce symptoms), and symptoms occur or worsen during periods of rest and in the evening and night. However, RLS is closely associated with periodic limb movement, which shows typical stererotyped limb movements. In the International Classification of Sleep Disorders, 3rd edition, sleep disturbances or daytime symptoms are prerequiste for a diagnosis of SRMD. We here review diagnosis and treatment of SRMD. PMID:26065126

  11. Sleep Problems and ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2008-05-01

    Full Text Available The prevalence of sleep problems and their associations with quality of life (QOL, school attendance, and family impacts in children with ADHD were determined in a study at Royal Children's Hospital, University of Melbourne, Australia.

  12. Psoriasis and Sleep Apnea

    DEFF Research Database (Denmark)

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

    2016-01-01

    , 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......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......) for sleep apnea were 1.30 (1.17-1.44), 1.65 (1.23-2.22), and 1.75 (1.35-2.26) in subjects with mild and severe psoriasis, and psoriatic arthritis, and IRRs for mild and severe psoriasis, and psoriatic arthritis in sleep apnea without continuous positive airway pressure (CPAP) therapy were 1.62 (1...

  13. Psoriasis and Sleep Apnea

    DEFF Research Database (Denmark)

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

    2015-01-01

    , 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......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......) for sleep apnea were 1.30 (1.17-1.44), 1.65 (1.23-2.22), and 1.75 (1.35-2.26) in subjects with mild and severe psoriasis, and psoriatic arthritis, and IRRs for mild and severe psoriasis, and psoriatic arthritis in sleep apnea without continuous positive airway pressure (CPAP) therapy were 1.62 (1...

  14. Sleep after laparoscopic cholecystectomy

    DEFF Research Database (Denmark)

    Rosenberg-Adamsen, S; Skarbye, M; Wildschiødtz, G;

    1996-01-01

    .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...... compared with the preoperative night. Comparison of our results with previous studies on SWS and REM sleep disturbances after open laparotomy, suggests that the magnitude of surgery or administration of opioids, or both, may be important factors in the development of postoperative sleep disturbances.......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...

  15. 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...

  16. Sleep in trigeminal autonomic cephalagias

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...... older study suggests chronic paroxysmal hemicranias may be locked to REM sleep but otherwise the relation is unknown. Reports indicate that CH and obstructive sleep apnoea are associated in some individuals but results are diverging. Single cases show improvement of CH upon treatment of sleep apnoea...

  17. 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.

  18. Artificial organisms that sleep.

    OpenAIRE

    Mirolli, Marco; Parisi, Domenico

    2003-01-01

    Abstract Populations of artificial organisms live in an environment in which light is cyclically present (day) or absent (night). Since being active during night is non-adaptive (activity consumes energy which is not compensated by the food found at night) the organisms evolve a sleep/wake behavioral pattern of being active during daytime and sleeping during nighttime. When the population moves to a different environment that contains "caves", they have to get out of a cave although the dark ...

  19. Reweighted Wake-Sleep

    OpenAIRE

    Bornschein, Jörg; Bengio, Yoshua

    2014-01-01

    Training deep directed graphical models with many hidden variables and performing inference remains a major challenge. Helmholtz machines and deep belief networks are such models, and the wake-sleep algorithm has been proposed to train them. The wake-sleep algorithm relies on training not just the directed generative model but also a conditional generative model (the inference network) that runs backward from visible to latent, estimating the posterior distribution of latent given visible. We...

  20. Sleep deprivation and depression

    OpenAIRE

    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 antidepressant effects. A large number of studies have followed these observations. The purpose of the studies presented in this thesis was to evaluate the clinical usefulness of TSD and related procedures for ...

  1. Sleep in thyrotoxicosis

    OpenAIRE

    G R Sridhar; Venkata Putcha; Lakshmi, G.

    2011-01-01

    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 slee...

  2. Sleep enhances category learning

    OpenAIRE

    Djonlagic, Ina; Rosenfeld, Andrew; Shohamy, Daphna; Myers, Catherine; Gluck, Mark; Stickgold, Robert

    2009-01-01

    The ability to categorize objects and events in the world around us is a fundamental and critical aspect of human learning. We trained healthy adults on a probabilistic category-learning task in two different training modes. The aim of this study was to see whether either form of probabilistic category learning (feedback or observational) undergoes subsequent enhancement during sleep. Our results suggest that after training, a good night of sleep can lead to improved performance the following...

  3. Complex Sleep Apnea Syndrome

    OpenAIRE

    Muhammad Talha Khan; Rose Amy Franco

    2014-01-01

    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, continu...

  4. Sleep EEG analysis

    OpenAIRE

    Vávrová, Eva

    2014-01-01

    This thesis deals with the analysis of EEG during various sleep stages, which is done by calculating the selected parameters from the time and frequency domain. These parameters are calculated from individual segments of EEG signals that correspond with various sleep stages. Based on the analysis it decides which EEG parameters are appropriate for the automatic detection of the phases and which method is more suitable for evaluation of data in hypnogram. The programme MATLAB was used for the ...

  5. Sleep and psychiatry

    OpenAIRE

    Abad, Vivien C.; Guilleminault, Christian

    2005-01-01

    Psychiatric disorders constitute 15.4% of the disease burden in established market economies. Many psychiatric disorders are associated with sleep disturbances, and the relationship is often bidirectional. This paper reviews the prevalence of various psychiatric disorders, their clinical presentation, and their association with sleep disorders. Among the psychiatric disorders reviewed are affective disorders, psychosis, anxiety disorders (including post-traumatic stress disorder), substance a...

  6. Sleep and anxiety disorders

    OpenAIRE

    Staner, Luc

    2003-01-01

    Sleep disturbances-particularly insomnia - are highly prevalent in anxiety disorders and complaints such as insomnia or nightmares have even been incorporated in some anxiety disorder definitions, such as generalized anxiety disorder and posttraumatic stress disorder. In the first part of this review, the relationship between sleep and anxiety is discussed in terms of adaptive response to stress. Recent studies suggested that the corticotropin-releasing hormone system and the locus ceruleus-a...

  7. 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.

  8. A new generation of T7 RNA polymerase-independent inducible expression plasmids for Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Jack Sunter

    Full Text Available Expression of transgenes is central to forward and reverse genetic analysis in Trypanosoma brucei. The inducible expression of transgenes in trypanosomes is based on the tetracycline repressor binding to a tetracycline operator to prevent transcription in the absence of tetracycline. The same inducible system is used to produce double-stranded RNA for RNAi knockdown of target genes. This study describes a new plasmid pSPR2.1 that drives consistent high-level expression of tetracycline repressor in procyclic form trypanosomes. A complementary expression plasmid, p3227, was constructed. The major difference between this and current plasmids is the separation of the inducible transgene and selectable marker promoters by the plasmid backbone. The plasmid p3227 was able to support inducible expression in cell lines containing pSPR2.1 as well as the established Lister 427 29-13 cell line. p3666, a derivative of p3227, was made for inducible expression of stem loop RNAi constructs and was effective for knockdown of DRBD3, which had proved problematic using existing RNAi plasmids with head-to-head promoters. The plasmid system was also able to support inducible transgene expression and DRBD3 RNAi knockdown in bloodstream form cells expressing tetracycline repressor from an integrated copy of the plasmid pHD1313.

  9. Immune Evasion Strategies of Trypanosoma brucei within the Mammalian Host: Progression to Pathogenicity

    Science.gov (United States)

    Stijlemans, Benoît; Caljon, Guy; Van Den Abbeele, Jan; Van Ginderachter, Jo A.; Magez, Stefan; De Trez, Carl

    2016-01-01

    The diseases caused by African trypanosomes (AT) are of both medical and veterinary importance and have adversely influenced the economic development of sub-Saharan Africa. Moreover, so far not a single field applicable vaccine exists, and chemotherapy is the only strategy available to treat the disease. These strictly extracellular protozoan parasites are confronted with different arms of the host’s immune response (cellular as well as humoral) and via an elaborate and efficient (vector)–parasite–host interplay they have evolved efficient immune escape mechanisms to evade/manipulate the entire host immune response. This is of importance, since these parasites need to survive sufficiently long in their mammalian/vector host in order to complete their life cycle/transmission. Here, we will give an overview of the different mechanisms AT (i.e. T. brucei as a model organism) employ, comprising both tsetse fly saliva and parasite-derived components to modulate host innate immune responses thereby sculpturing an environment that allows survival and development within the mammalian host.

  10. 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. PMID:25896436

  11. 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.

  12. 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.

  13. 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.

  14. The isolation and partial characterization of the plasma membrane from Trypanosoma brucei.

    Science.gov (United States)

    Voorheis, H P; Gale, J S; Owen, M J; Edwards, W

    1979-04-15

    Whole sheets of plasma membrane, each with their attached flagellum, were purified from Trypanosoma brucei. The method devised for their isolation included a new technique of cell breakage that used a combination of osmotic stress followed by mechanical sheer and avoided the problem of extreme vesiculation as well as the trapping of organelles in cell 'ghosts'. The purified membranes all contained the pellicular microtubular array. The antigenic surface coat was completely released from the plasma membrane during the isolation procedure. The membranes had a very high cholesterol/phospholipid ratio (1.54). A large proportion (42%) of the cellular DNA was recovered in the plasma-membrane fraction unless a step involving deoxyribonuclease treatment, which decreased the DNA content to less than 13%, was included before secrose-density gradient centrifugation. This step also aided the separation of plasma membranes from other cellular components. The ouabain-sensitive Na+ + K+-stimulated adenosine triphosphatase and adenylate cyclase co-purified with the plasma membranes. Although 5'-nucleotidase was thought to be a plasma-membrane component, it was easily detached from the membrane. The purified membranes were essentially free of L-alanine-alpha-oxoglutarate aminotransferase, L-asparte-alpha-oxoglutarate aminotransferase, malate dehydrogenase, oligomycin-sensitive adenosine triphosphatase, glucose 6-phosphatase, Mg2+-stimulated p-nitrophenyl phosphatase and catalase. PMID:486094

  15. Identification of paralogous life-cycle stage specific cytoskeletal proteins in the parasite Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Neil Portman

    Full Text Available The life cycle of the African trypanosome Trypanosoma brucei, is characterised by a transition between insect and mammalian hosts representing very different environments that present the parasite with very different challenges. These challenges are met by the expression of life-cycle stage-specific cohorts of proteins, which function in systems such as metabolism and immune evasion. These life-cycle transitions are also accompanied by morphological rearrangements orchestrated by microtubule dynamics and associated proteins of the subpellicular microtubule array. Here we employed a gel-based comparative proteomic technique, Difference Gel Electrophoresis, to identify cytoskeletal proteins that are expressed differentially in mammalian infective and insect form trypanosomes. From this analysis we identified a pair of novel, paralogous proteins, one of which is expressed in the procyclic form and the other in the bloodstream form. We show that these proteins, CAP51 and CAP51V, localise to the subpellicular corset of microtubules and are essential for correct organisation of the cytoskeleton and successful cytokinesis in their respective life cycle stages. We demonstrate for the first time redundancy of function between life-cycle stage specific paralogous sets in the cytoskeleton and reveal modification of cytoskeletal components in situ prior to their removal during differentiation from the bloodstream form to the insect form. These specific results emphasise a more generic concept that the trypanosome genome encodes a cohort of cytoskeletal components that are present in at least two forms with life-cycle stage-specific expression.

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    Daniel Nilsson

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

  18. Identification of the mitochondrially encoded subunit 6 of F1FO ATPase in Trypanosoma brucei.

    Science.gov (United States)

    Škodová-Sveráková, Ingrid; Horváth, Anton; Maslov, Dmitri A

    2015-06-01

    Kinetoplast maxicircle DNA of trypanosomatids encodes eighteen proteins. RNA editing is required to confer translatability to mRNA for twelve of these. Sequence conservation of the predicted hydrophobic polypeptides indicates that they represent functional components of the respiratory chain. Yet, so far only two of those, cytochrome c oxidase subunit I and apocytochrome b of cytochrome c reductase, have been identified with biochemical methods. Here we report on identification of A6 subunit of F1FO ATPase encoded by a pan-edited mRNA in Trypanosoma brucei. The polypeptide was present among the (35)S-labeled mitochondrial translation products characterized by anomalous migration in denaturing 2D gels. It was identified as an ATPase subunit by co-migration with this complex in Blue Native 2D gels. A partial N-terminal sequence of the corresponding polypeptide present in the gel-purified ATPase complex from Leishmania tarentolae was consistent with the predicted A6 sequence. PMID:26276057

  19. 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.

  20. 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.

  1. A sleep state during C. elegans development

    OpenAIRE

    Nelson, Matthew D.; Raizen, David M.

    2013-01-01

    Caenorhabditis elegans is the simplest animal shown to sleep. It sleeps during lethargus, a larval transition stage. Behavior during lethargus has the sleep properties of a specific quiescent posture and elevated arousal threshold that are reversible to strong stimulation and of increased sleep drive following sleep deprivation. Genetic similarities between sleep regulation during C. elegans lethargus and sleep regulation in other animals point to a sleep state that was an evolutionarily ance...

  2. Can non-REM sleep be depressogenic?

    OpenAIRE

    Beersma, Domien G. M.; Hoofdakker, Rutger H. van den

    1992-01-01

    Sleep and mood are clearly interrelated in major depression, as shown by the antidepressive effects of various experiments, such as total sleep deprivation, partial sleep deprivation, REM sleep deprivation, and temporal shifts of the sleep period. The prevailing hypotheses explaining these effects concern the antidepressant potency of the suppression of either REM sleep or non-REM sleep. This issue is discussed in the light of present knowledge of the kinetics of non-REM sleep intensity, REM ...

  3. 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.

  4. Sleep · 8: Paediatric obstructive sleep apnoea

    OpenAIRE

    Nixon, G; Brouillette, R

    2005-01-01

    In the past 25 years there has been increasing recognition of obstructive sleep apnoea (OSA) as a common condition of childhood. Morbidity includes impairment of growth, cardiovascular complications, learning impairment, and behavioural problems. Diagnosis and treatment of this condition in children differs in many respects from that in adults. We review here the key features of paediatric OSA, highlighting differences from adult OSA, and suggest future directions for research.

  5. Do birds sleep in flight?

    Science.gov (United States)

    Rattenborg, Niels C.

    2006-09-01

    The following review examines the evidence for sleep in flying birds. The daily need to sleep in most animals has led to the common belief that birds, such as the common swift ( Apus apus), which spend the night on the wing, sleep in flight. The electroencephalogram (EEG) recordings required to detect sleep in flight have not been performed, however, rendering the evidence for sleep in flight circumstantial. The neurophysiology of sleep and flight suggests that some types of sleep might be compatible with flight. As in mammals, birds exhibit two types of sleep, slow-wave sleep (SWS) and rapid eye-movement (REM) sleep. Whereas, SWS can occur in one or both brain hemispheres at a time, REM sleep only occurs bihemispherically. During unihemispheric SWS, the eye connected to the awake hemisphere remains open, a state that may allow birds to visually navigate during sleep in flight. Bihemispheric SWS may also be possible during flight when constant visual monitoring of the environment is unnecessary. Nevertheless, the reduction in muscle tone that usually accompanies REM sleep makes it unlikely that birds enter this state in flight. Upon landing, birds may need to recover the components of sleep that are incompatible with flight. Periods of undisturbed postflight recovery sleep may be essential for maintaining adaptive brain function during wakefulness. The recent miniaturization of EEG recording devices now makes it possible to measure brain activity in flight. Determining if and how birds sleep in flight will contribute to our understanding of a largely unexplored aspect of avian behavior and may also provide insight into the function of sleep.

  6. 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

  7. Sleep disorders in hemodialysis patients.

    Science.gov (United States)

    Sabry, Alaa A; Abo-Zenah, Hamdy; Wafa, Ehab; Mahmoud, Khaled; El-Dahshan, Khaled; Hassan, Ahmed; Abbas, Tarek Medhat; Saleh, Abd El-Baset M; Okasha, Kamal

    2010-03-01

    The prevalence of sleep disorders is higher in patients with kidney failure than the general population. We studied the prevalence of sleep disorders in 88 (mean age; 41.59 +/- 16.3 years) chronic hemodialysis (HD) patients at the Urology and Nephrology Center, Mansoura University, Egypt over 4-month period. The investigated sleep disorders included insomnia, restless leg syndrome (RLS), obstructive sleep apnea syndrome (OSAS), excessive daytime sleepiness (EDS), narcolepsy and sleep walking, and we used a questionnaire in accordance with those of the International Restless Legs Syndrome Study Group, the Berlin questionnaire, Italian version of Epworth Sleepiness Scale, International Classification of Sleep Disorders, and the specific questions of Hatoum's sleep questionnaire. The prevalence of sleep disorders was 79.5% in our patients, and the most common sleep abnormality was insomnia (65.9%), followed by RLS (42%), OSAS (31.8%), snoring (27.3%), EDS (27.3%), narcolepsy (15.9%), and sleep walking (3.4%). Insomnia correlated with anemia (r=0.31, P= 0.003), anxiety (r=0.279, P= 0.042), depression (r=0.298, P= 0.24) and RLS (r=0.327, P= 0.002). Also, RLS correlated with hypoalbuminemia (r=0.41, P= Sleep disorders are quite common in the HD patients, especially those who are anemic and hypoalbuminemic. Assessment of sleep quality, preferably with polysomnography, is necessary to confirm our results. Interventional studies for management of sleep disorders in HD patients are warranted. PMID:20228517

  8. Optogenetically induced sleep spindle rhythms alter sleep architectures in mice

    OpenAIRE

    Kim, Angela; Latchoumane, Charles; Lee, Soojung; Kim, Guk Bae; Cheong, Eunji; Augustine, George J.; Shin, Hee-Sup

    2012-01-01

    Sleep spindles are rhythmic patterns of neuronal activity generated within the thalamocortical circuit. Although spindles have been hypothesized to protect sleep by reducing the influence of external stimuli, it remains to be confirmed experimentally whether there is a direct relationship between sleep spindles and the stability of sleep. We have addressed this issue by using in vivo photostimulation of the thalamic reticular nucleus of mice to generate spindle oscillations that are structura...

  9. Sleep and Delinquency: Does the Amount of Sleep Matter?

    Science.gov (United States)

    Clinkinbeard, Samantha S.; Simi, Pete; Evans, Mary K.; Anderson, Amy L.

    2011-01-01

    Sleep, a key indicator of health, has been linked to a variety of indicators of well-being such that people who get an adequate amount generally experience greater well-being. Further, a lack of sleep has been linked to a wide range of negative developmental outcomes, yet sleep has been largely overlooked among researchers interested in adolescent…

  10. Sleep, its regulation and possible mechanisms of sleep disturbances.

    Science.gov (United States)

    Porkka-Heiskanen, T; Zitting, K-M; Wigren, H-K

    2013-08-01

    The state of sleep consists of different phases that proceed in successive, tightly regulated order through the night forming a physiological program, which for each individual is different but stabile from one night to another. Failure to accomplish this program results in feeling of unrefreshing sleep and tiredness in the morning. The program core is constructed by genetic factors but regulated by circadian rhythm and duration and intensity of day time brain activity. Many environmental factors modulate sleep, including stress, health status and ingestion of vigilance-affecting nutrients or medicines (e.g. caffeine). Acute sleep loss results in compromised cognitive performance, memory deficits, depressive mood and involuntary sleep episodes during the day. Moreover, prolonged sleep curtailment has many adverse health effects, as evidenced by both epidemiological and experimental studies. These effects include increased risk for depression, type II diabetes, obesity and cardiovascular diseases. In addition to voluntary restriction of sleep, shift work, irregular working hours, jet lag and stress are important factors that induce curtailed or bad quality sleep and/or insomnia. This review covers the current theories on the function of normal sleep and describes current knowledge on the physiologic effects of sleep loss. It provides insights into the basic mechanisms of the regulation of wakefulness and sleep creating a theoretical background for understanding different disturbances of sleep. PMID:23746394

  11. 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.

  12. Functional neuroimaging of sleep disorders

    International Nuclear Information System (INIS)

    Sleep disorders may affect the health and normal life of human badly. However, the pathophysiology underlying adult sleep disorders is still unclear. Functional neuroimaging can be used to investigate whether sleep disorders are associated with specific changes in brain structure or regional activity. This paper reviews functional brain imaging findings in major intrinsic sleep disorders (i.e., idiopathic insomnia, narcolepsy, and obstructive sleep apnea) and in abnormal motor behavior during sleep (i.e., periodic limb movement disorder and REM sleep behavior disorder). Metabolic/functional investigations (positron emission tomography, single photon emission computed tomography, functional magnetic resonance imaging) are mainly reviewed, as well as neuroanatomical assessments (voxel-based morphometry, magnetic resonance spectroscopy). Meanwhile, here are some brief introduction of different kinds of sleep disorders. (authors)

  13. Common Sleep Problems (For Teens)

    Science.gov (United States)

    ... Narcolepsy Sleepwalking What Should I Do? en español Problemas comunes del sueño Garrett had a hard time ... them include certain medicines, and consuming drugs or alcohol. Sleep deprivation (getting too little sleep) also can ...

  14. 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.

  15. THE MULTIPLE ROLES OF CYCLIN E1 IN CONTROLLING CELL CYCLE PROGRESSION AND CELLULAR MORPHOLOGY OF TRYPANOSOMA BRUCEI

    OpenAIRE

    Gourguechon, Stéphane; Savich, Jason M.; Ching C Wang

    2007-01-01

    Regulation of eukaryotic cell cycle progression requires sequential activation and inactivation of cyclin-dependent kinases. Previous RNA interference (RNAi) experiments in Trypanosoma brucei indicated that cyclin E1, cdc2-related kinase (CRK)1 and CRK2 are involved in regulating G1/S transition, whereas cyclin B2 and CRK3 play a pivotal role in controlling the G2/M checkpoint. To search for potential interactions between the other cyclins and CRKs that may not have been revealed by the RNAi ...

  16. Sleep Deprivation and False Memories

    OpenAIRE

    Frenda, SJ; Patihis, L; Loftus, EF; Lewis, HC; Fenn, KM

    2014-01-01

    © The Author(s) 2014. 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,...

  17. Sleep, noise and health: Review

    OpenAIRE

    Mia Zaharna; Christian Guilleminault

    2010-01-01

    Sleep is a physiologic recuperative state that may be negatively affected by factors such as psychosocial and work stress as well as external stimuli like noise. Chronic sleep loss is a common problem in today′s society, and it may have significant health repercussions such as cognitive impairment, and depressed mood, and negative effects on cardiovascular, endocrine, and immune function. This article reviews the definition of disturbed sleep versus sleep deprivation as well as the effects of...

  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. Experiences with an in-training community service model in the control of zoonotic sleeping sickness in Uganda.

    Science.gov (United States)

    Waiswa, Charles; Kabasa, John D

    2010-01-01

    By 2006, the acute and zoonotic Tripanosoma brucei rhodesiense sleeping sickness in Uganda was spreading northward, leading to fear of a merger with the chronic Tripanosoma brucei gambiese type that affects people in the northwest of the country. Eliminating infection in cattle was urgent because they had been confirmed to be spreading the zoonotic type, and eliminating infection would reduce the animal reservoir and subsequently reduce transmission of sleeping sickness. In this article, we describe how the staff and students of the Faculty of Veterinary Medicine, Makerere University, adjusted their approach to training veterinary students who could provide the urgently needed manpower to enable the community to halt the disease's spread. Because it was not usual for university staff and students to implement disease control activities, the government of Uganda had to delegate this responsibility to Makerere University. In turn, the university had to explore available opportunities in its training and outreach mandates. A model was developed that proved to be an effective hands-on training strategy while helping to control a disease that was threatening the health of people in a community that was just recovering from an armed rebellion. In total, 66 students and supervisors participated in the 10-week-long mass treatment activities in the target area and treated more than 190,000 out of 220,000 targeted (>86%) cattle with diminazene aceturate and deltamethrin. Also, the graduates' performance improved, as indicated by 43.5% of graduates securing employment within less than a month after completing the course. PMID:20847337

  20. 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. PMID:20442123

  1. [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. PMID:21077298

  2. Sleep in cluster headache

    DEFF Research Database (Denmark)

    Barloese, M C J; Jennum, P J; Lund, N T;

    2015-01-01

    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.......0037), longer REM latency (2.0 vs. 1.2 h, P = 0.0012) and fewer arousals (7.34 vs. 14.1, P = 0.003) in CH patients. There was no difference in prevalence of sleep apnea between patients (38%) and matched controls (32%, P = 0.64) although the apnea index in patients was numerically higher (mean apnea...

  3. 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.

  4. 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

  5. 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…

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. Respiratory rate variability in sleeping adults without obstructive sleep apnea.

    Science.gov (United States)

    Gutierrez, Guillermo; Williams, Jeffrey; Alrehaili, Ghadah A; McLean, Anna; Pirouz, Ramin; Amdur, Richard; Jain, Vivek; Ahari, Jalil; Bawa, Amandeep; Kimbro, Shawn

    2016-09-01

    Characterizing respiratory rate variability (RRV) in humans during sleep is challenging, since it requires the analysis of respiratory signals over a period of several hours. These signals are easily distorted by movement and volitional inputs. We applied the method of spectral analysis to the nasal pressure transducer signal in 38 adults with no obstructive sleep apnea, defined by an apnea-hypopnea index sleep stages, including wakefulness. The nasal pressure transducer signal was acquired at 100 Hz and consecutive frequency spectra were generated for the length of the PSG with the Fast Fourier Transform. For each spectrum, we computed the amplitude ratio of the first harmonic peak to the zero frequency peak (H1/DC), and defined as RRV as (100 - H1/DC) %. RRV was greater during wakefulness compared to any sleep stage, including rapid-eye-movement. Furthermore, RRV correlated with the depth of sleep, being lowest during N3. Patients spent most their sleep time supine, but we found no correlation between RRV and body position. There was a correlation between respiratory rate and sleep stage, being greater in wakefulness than in any sleep stage. We conclude that RRV varies according to sleep stage. Moreover, spectral analysis of nasal pressure signal appears to provide a valid measure of RRV during sleep. It remains to be seen if the method can differentiate normal from pathological sleep patterns. PMID:27597768

  13. Sleep in elite athletes and nutritional interventions to enhance sleep.

    Science.gov (United States)

    Halson, Shona L

    2014-05-01

    Sleep has numerous important physiological and cognitive functions that may be particularly important to elite athletes. Recent evidence, as well as anecdotal information, suggests that athletes may experience a reduced quality and/or quantity of sleep. Sleep deprivation can have significant effects on athletic performance, especially submaximal, prolonged exercise. Compromised sleep may also influence learning, memory, cognition, pain perception, immunity and inflammation. Furthermore, changes in glucose metabolism and neuroendocrine function as a result of chronic, partial sleep deprivation may result in alterations in carbohydrate metabolism, appetite, food intake and protein synthesis. These factors can ultimately have a negative influence on an athlete's nutritional, metabolic and endocrine status and hence potentially reduce athletic performance. Research has identified a number of neurotransmitters associated with the sleep-wake cycle. These include serotonin, gamma-aminobutyric acid, orexin, melanin-concentrating hormone, cholinergic, galanin, noradrenaline, and histamine. Therefore, nutritional interventions that may act on these neurotransmitters in the brain may also influence sleep. Carbohydrate, tryptophan, valerian, melatonin and other nutritional interventions have been investigated as possible sleep inducers and represent promising potential interventions. In this review, the factors influencing sleep quality and quantity in athletic populations are examined and the potential impact of nutritional interventions is considered. While there is some research investigating the effects of nutritional interventions on sleep, future research may highlight the importance of nutritional and dietary interventions to enhance sleep. PMID:24791913

  14. Nap sleep spindle correlates of intelligence

    OpenAIRE

    Ujma, Péter P.; Róbert Bódizs; Ferenc Gombos; Johannes Stintzing; Konrad, Boris N.; Lisa Genzel; Axel Steiger; Martin Dresler

    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 fluid intelligence scores, however more recently it has been shown that only few sleep spindle measures correlate with intelligence in females, and none in males. Sleep spindle regulation underlies a...

  15. Metabolic consequences of sleep and circadian disorders

    OpenAIRE

    Depner, Christopher M.; Stothard, Ellen R.; Wright, Kenneth P.

    2014-01-01

    Sleep and circadian rhythms modulate or control daily physiological patterns with importance for normal metabolic health. Sleep deficiencies associated with insufficient sleep schedules, insomnia with short-sleep duration, sleep apnea, narcolepsy, circadian misalignment, shift work, night eating syndrome and sleep-related eating disorder may all contribute to metabolic dysregulation. Sleep deficiencies and circadian disruption associated with metabolic dysregulation may contribute to weight g...

  16. Sleep Monitoring System Using Kinect Sensor

    OpenAIRE

    Jaehoon Lee; Min Hong; Sungyong Ryu

    2015-01-01

    Sleep activity is one of crucial factors for determining the quality of human life. However, a traditional sleep monitoring system onerously requires many devices to be attached to human body for achieving sleep related information. In this paper, we proposed and implemented the sleep monitoring system which can detect the sleep movement and posture during sleep using a Microsoft Kinect v2 sensor without any body attached devices. The proposed sleep monitoring system can readily gather the sl...

  17. 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.

  18. A novel high-throughput activity assay for the Trypanosoma brucei editosome enzyme REL1 and other RNA ligases

    Science.gov (United States)

    Zimmermann, Stephan; Hall, Laurence; Riley, Sean; Sørensen, Jesper; Amaro, Rommie E.; Schnaufer, Achim

    2016-01-01

    The protist parasite Trypanosoma brucei causes Human African trypanosomiasis (HAT), which threatens millions of people in sub-Saharan Africa. Without treatment the infection is almost always lethal. Current drugs for HAT are difficult to administer and have severe side effects. Together with increasing drug resistance this results in urgent need for new treatments. T. brucei and other trypanosomatid pathogens require a distinct form of post-transcriptional mRNA modification for mitochondrial gene expression. A multi-protein complex called the editosome cleaves mitochondrial mRNA, inserts or deletes uridine nucleotides at specific positions and re-ligates the mRNA. RNA editing ligase 1 (REL1) is essential for the re-ligation step and has no close homolog in the mammalian host, making it a promising target for drug discovery. However, traditional assays for RELs use radioactive substrates coupled with gel analysis and are not suitable for high-throughput screening of compound libraries. Here we describe a fluorescence-based REL activity assay. This assay is compatible with a 384-well microplate format and sensitive, satisfies statistical criteria for high-throughput methods and is readily adaptable for other polynucleotide ligases. We validated the assay by determining kinetic properties of REL1 and by identifying REL1 inhibitors in a library of small, pharmacologically active compounds. PMID:26400159

  19. TbPIF5 is a Trypanosoma brucei mitochondrial DNA helicase involved in processing of minicircle Okazaki fragments.

    Directory of Open Access Journals (Sweden)

    Beiyu Liu

    2009-09-01

    Full Text Available Trypanosoma brucei's mitochondrial genome, kinetoplast DNA (kDNA, is a giant network of catenated DNA rings. The network consists of a few thousand 1 kb minicircles and several dozen 23 kb maxicircles. Here we report that TbPIF5, one of T. brucei's six mitochondrial proteins related to Saccharomyces cerevisiae mitochondrial DNA helicase ScPIF1, is involved in minicircle lagging strand synthesis. Like its yeast homolog, TbPIF5 is a 5' to 3' DNA helicase. Together with other enzymes thought to be involved in Okazaki fragment processing, TbPIF5 localizes in vivo to the antipodal sites flanking the kDNA. Minicircles in wild type cells replicate unidirectionally as theta-structures and are unusual in that Okazaki fragments are not joined until after the progeny minicircles have segregated. We now report that overexpression of TbPIF5 causes premature removal of RNA primers and joining of Okazaki fragments on theta structures. Further elongation of the lagging strand is blocked, but the leading strand is completed and the minicircle progeny, one with a truncated H strand (ranging from 0.1 to 1 kb, are segregated. The minicircles with a truncated H strand electrophorese on an agarose gel as a smear. This replication defect is associated with kinetoplast shrinkage and eventual slowing of cell growth. We propose that TbPIF5 unwinds RNA primers after lagging strand synthesis, thus facilitating processing of Okazaki fragments.

  20. 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.

  1. Tracking the Biogenesis and Inheritance of Subpellicular Microtubule in Trypanosoma brucei with Inducible YFP-α-Tubulin

    Directory of Open Access Journals (Sweden)

    Omar Sheriff

    2014-01-01

    Full Text Available The microtubule cytoskeleton forms the most prominent structural system in Trypanosoma brucei, undergoing extensive modifications during the cell cycle. Visualization of tyrosinated microtubules leads to a semiconservative mode of inheritance, whereas recent studies employing microtubule plus end tracking proteins have hinted at an asymmetric pattern of cytoskeletal inheritance. To further the knowledge of microtubule synthesis and inheritance during T. brucei cell cycle, the dynamics of the microtubule cytoskeleton was visualized by inducible YFP-α-tubulin expression. During new flagellum/flagellum attachment zone (FAZ biogenesis and cell growth, YFP-α-tubulin was incorporated mainly between the old and new flagellum/FAZ complexes. Cytoskeletal modifications at the posterior end of the cells were observed with EB1, a microtubule plus end binding protein, particularly during mitosis. Additionally, the newly formed microtubules segregated asymmetrically, with the daughter cell inheriting the new flagellum/FAZ complex retaining most of the new microtubules. Together, our results suggest an intimate connection between new microtubule formation and new FAZ assembly, consequently leading to asymmetric microtubule inheritance and cell division.

  2. Independent analysis of the flagellum surface and matrix proteomes provides insight into flagellum signaling in mammalian-infectious Trypanosoma brucei.

    Science.gov (United States)

    Oberholzer, Michael; Langousis, Gerasimos; Nguyen, HoangKim T; Saada, Edwin A; Shimogawa, Michelle M; Jonsson, Zophonias O; Nguyen, Steven M; Wohlschlegel, James A; Hill, Kent L

    2011-10-01

    The flagellum of African trypanosomes is an essential and multifunctional organelle that functions in motility, cell morphogenesis, and host-parasite interaction. Previous studies of the trypanosome flagellum have been limited by the inability to purify flagella without first removing the flagellar membrane. This limitation is particularly relevant in the context of studying flagellum signaling, as signaling requires surface-exposed proteins in the flagellar membrane and soluble signaling proteins in the flagellar matrix. Here we employ a combination of genetic and mechanical approaches to purify intact flagella from the African trypanosome, Trypanosoma brucei, in its mammalian-infectious stage. We combined flagellum purification with affinity-purification of surface-exposed proteins to conduct independent proteomic analyses of the flagellum surface and matrix fractions. The proteins identified encompass a broad range of molecular functionalities, including many predicted to function in signaling. Immunofluorescence and RNA interference studies demonstrate flagellum localization and function for proteins identified and provide insight into mechanisms of flagellum attachment and motility. The flagellum surface proteome includes many T. brucei-specific proteins and is enriched for proteins up-regulated in the mammalian-infectious stage of the parasite life-cycle. The combined results indicate that the flagellum surface presents a diverse and dynamic host-parasite interface that is well-suited for host-parasite signaling. PMID:21685506

  3. Genome-wide Analysis Reveals Extensive Functional Interaction between DNA Replication Initiation and Transcription in the Genome of Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Calvin Tiengwe

    2012-07-01

    Full Text Available Identification of replication initiation sites, termed origins, is a crucial step in understanding genome transmission in any organism. Transcription of the Trypanosoma brucei genome is highly unusual, with each chromosome comprising a few discrete transcription units. To understand how DNA replication occurs in the context of such organization, we have performed genome-wide mapping of the binding sites of the replication initiator ORC1/CDC6 and have identified replication origins, revealing that both localize to the boundaries of the transcription units. A remarkably small number of active origins is seen, whose spacing is greater than in any other eukaryote. We show that replication and transcription in T. brucei have a profound functional overlap, as reducing ORC1/CDC6 levels leads to genome-wide increases in mRNA levels arising from the boundaries of the transcription units. In addition, ORC1/CDC6 loss causes derepression of silent Variant Surface Glycoprotein genes, which are critical for host immune evasion.

  4. 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.

  5. 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.

    2014-01-01

    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. PMID:25340575

  6. 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

  7. 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.

  8. 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...

  9. Sleep Dysfunction and Gastrointestinal Diseases.

    Science.gov (United States)

    Khanijow, Vikesh; Prakash, Pia; Emsellem, Helene A; Borum, Marie L; Doman, David B

    2015-12-01

    Sleep deprivation and impaired sleep quality have been associated with poor health outcomes. Many patients experience sleep disturbances, which can increase the risk of medical conditions such as hypertension, obesity, stroke, and heart disease as well as increase overall mortality. Recent studies have suggested that there is a strong association between sleep disturbances and gastrointestinal diseases. Proinflammatory cytokines, such as tumor necrosis factor, interleukin-1, and interleukin-6, have been associated with sleep dysfunction. Alterations in these cytokines have been seen in certain gastrointestinal diseases, such as gastroesophageal reflux disease, inflammatory bowel disease, liver disorders, and colorectal cancer. It is important for gastroenterologists to be aware of the relationship between sleep disorders and gastrointestinal illnesses to ensure good care for patients. This article reviews the current research on the interplay between sleep disorders, immune function, and gastrointestinal diseases. PMID:27134599

  10. 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 Sleep Quality Index increased (indicating decreased subjective sleep quality) and percentage REM sleep decreased, while REM sleep latency increased (Ps sleep quality and adverse changes in REM sleep were associated with diminished vasodilation, which could link sleep disturbances to cardiovascular disease.

  11. 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

  12. 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...

  13. 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.

  14. Changing your sleep habits

    Science.gov (United States)

    ... 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 tells you to slow down or take a break.

  15. 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.

  16. 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.

  17. 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…

  18. 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.

  19. Sleep smart-optimizing sleep for declarative learning and memory.

    Science.gov (United States)

    Feld, Gordon B; Diekelmann, Susanne

    2015-01-01

    The last decade has witnessed a spurt of new publications documenting sleep's essential contribution to the brains ability to form lasting memories. For the declarative memory domain, slow wave sleep (the deepest sleep stage) has the greatest beneficial effect on the consolidation of memories acquired during preceding wakefulness. The finding that newly encoded memories become reactivated during subsequent sleep fostered the idea that reactivation leads to the strengthening and transformation of the memory trace. According to the active system consolidation account, trace reactivation leads to the redistribution of the transient memory representations from the hippocampus to the long-lasting knowledge networks of the cortex. Apart from consolidating previously learned information, sleep also facilitates the encoding of new memories after sleep, which probably relies on the renormalization of synaptic weights during sleep as suggested by the synaptic homeostasis theory. During wakefulness overshooting potentiation causes an imbalance in synaptic weights that is countered by synaptic downscaling during subsequent sleep. This review briefly introduces the basic concepts and central findings of the research on sleep and memory, and discusses implications of this lab-based work for everyday applications to make the best possible use of sleep's beneficial effect on learning and memory. PMID:26029150

  20. 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.

  1. Sleep and Epilepsy: Strange Bedfellows No More

    OpenAIRE

    St. Louis, Erik K

    2011-01-01

    Ancient philosophers and theologians believed that altered consciousness freed the mind to prophesy the future, equating sleep with seizures. Only recently has the bidirectional influences of epilepsy and sleep upon one another received more substantive analysis. This article reviews the complex and increasingly recognized interrelationships between sleep and epilepsy. NREM sleep differentially activates interictal epileptiform discharges during slow wave (N3) sleep, while i...

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. Common sleep disorders in children.

    Science.gov (United States)

    Carter, Kevin A; Hathaway, Nathanael E; Lettieri, Christine F

    2014-03-01

    Up to 50% of children will experience a sleep problem. Early identification of sleep problems may prevent negative consequences, such as daytime sleepiness, irritability, behavioral problems, learning difficulties, motor vehicle crashes in teenagers, and poor academic performance. Obstructive sleep apnea occurs in 1% to 5% of children. Polysomnography is needed to diagnose the condition because it may not be detected through history and physical examination alone. Adenotonsillectomy is the primary treatment for most children with obstructive sleep apnea. Parasomnias are common in childhood; sleepwalking, sleep talking, confusional arousals, and sleep terrors tend to occur in the first half of the night, whereas nightmares are more common in the second half of the night. Only 4% of parasomnias will persist past adolescence; thus, the best management is parental reassurance and proper safety measures. Behavioral insomnia of childhood is common and is characterized by a learned inability to fall and/or stay asleep. Management begins with consistent implementation of good sleep hygiene practices, and, in some cases, use of extinction techniques may be appropriate. Delayed sleep phase disorder is most common in adolescence, presenting as difficulty falling asleep and awakening at socially acceptable times. Treatment involves good sleep hygiene and a consistent sleep-wake schedule, with nighttime melatonin and/or morning bright light therapy as needed. Diagnosing restless legs syndrome in children can be difficult; management focuses on trigger avoidance and treatment of iron deficiency, if present. PMID:24695508

  8. 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. PMID:20424573

  9. [Quality of sleep in students].

    Science.gov (United States)

    Micu, Alina; Cojocaru, Cristian; Luca, Gianina; Mihăescu, Traian

    2012-01-01

    Sleep quality is an important factor involved in students' learning process. Using different methods, actual studies suggest that complaints about sleep problems are common in young medical students. The aim of this study was to evaluate if is any relation between factors like medium and lifestyle among students of the University of Medicine and Pharmacy "Grigore T Popa" from Iaşi. The study group included 30 students (2 of them were excluded) who performed a polisomnography, self reported Epworth questionnaire and two weeks sleep diary. Coffee, energy drinks, green and black tea and alcohol intake were recorded. In our evaluation it was used sleep disturbance index (SDI), for sleep quality description. In those two weeks, the mean sleep hours was 7.8 (95% CI 7.6-8), greater in female than in male. The results suggest a significant correlation between psychical excitants and sleep fragmentation. More, excessive daytime somnolence declared is not in concordance with sleep quality observed in sleep recorded with polysomnography. It looks to be in correlation with bad sleep habits and psychical excitants intake. PMID:22545485

  10. Sleep disorders in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Sabry Alaa

    2010-01-01

    Full Text Available The prevalence of sleep disorders is higher in patients with kidney failure than the general population. We studied the prevalence of sleep disorders in 88 (mean age; 41.59 ± 16.3 years chronic hemodialysis (HD patients at the Urology and Nephrology Center, Mansoura Uni-versity, Egypt over 4-month period. The investigated sleep disorders included insomnia, restless leg syndrome (RLS, obstructive sleep apnea syndrome (OSAS, excessive daytime sleepiness (EDS, narcolepsy and sleep walking, and we used a questionnaire in accordance with those of the International Restless Legs Syndrome Study Group, the Berlin questionnaire, Italian version of Epworth Sleepiness Scale, International Classification of Sleep Disorders, and the specific ques-tions of Hatoum′s sleep questionnaire. The prevalence of sleep disorders was 79.5% in our pa-tients, and the most common sleep abnormality was insomnia (65.9%, followed by RLS (42%, OSAS (31.8%, snoring (27.3%, EDS (27.3%, narcolepsy (15.9%, and sleep walking (3.4%. Insomnia correlated with anemia (r=0.31, P= 0.003, anxiety (r=0.279, P= 0.042, depression (r=0.298, P= 0.24 and RLS (r=0.327, P= 0.002. Also, RLS correlated with hypoalbuminemia (r=0.41, P= < 0.0001, anemia (r=0.301 and P= 0.046, hyperphosphatemia (r=0.343 and P= 0.001. EDS correlated with OSAS (r=0.5, P= < 0.0001, snoring (r=0.341, P= 0.001, and social worry (r=0.27, P= 0.011. Sleep disorders are quite common in the HD patients, especially those who are anemic and hypoalbuminemic. Assessment of sleep quality, preferably with polysomno-graphy, is necessary to confirm our results. Interventional studies for management of sleep disor-ders in HD patients are warranted.

  11. 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).

  12. Dynamics of Sleep-Wake Transitions During Sleep

    OpenAIRE

    Lo, Chung-Chuan; Amaral, Luis A. Nunes; Havlin, Shlomo; Ivanov, Plamen Ch.; Penzel, Thomas; Peter, Joerg-Hermann; Stanley, H. Eugene

    2001-01-01

    We study the dynamics of the awakening during the night for healthy subjects and find that the wake and the sleep periods exhibit completely different behavior: the durations of wake periods are characterized by a scale-free power-law distribution, while the durations of sleep periods have an exponential distribution with a characteristic time scale. We find that the characteristic time scale of sleep periods changes throughout the night. In contrast, there is no measurable variation in the p...

  13. 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.

  14. 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.

  15. Overview on Sleep Bruxism for Sleep Medicine Clinicians.

    Science.gov (United States)

    Carra, Maria Clotilde; Huynh, Nelly; Fleury, Bernard; Lavigne, Gilles

    2015-09-01

    Sleep bruxism (SB) is a common sleep-related jaw motor disorder observed in 8% of the adult population. SB diagnosis is based on history of tooth grinding and clenching and is confirmed by the polysomnographic recording of the electromyographic activity of jaw muscles during sleep. SB may be associated with orofacial pain, headaches, and sleep-disordered breathing. Managing SB cannot be done without a comprehensive clinical and, when indicated, polysomnographic differential diagnosis of other comorbidities, which need to be taken into account to select the best treatment approach. PMID:26329448

  16. Diagnosing Sleep Disorders | NIH MedlinePlus the Magazine

    Science.gov (United States)

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

  17. Sleep On It: How Snoozing Strengthens Memories

    Science.gov (United States)

    ... External link, please review our exit disclaimer . Subscribe Sleep On It How Snoozing Strengthens Memories When you ... the best way to remember it is to sleep on it. That’s because sleeping helps strengthen memories ...

  18. 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. ...

  19. Sleep Disorders 6 Times Higher Among Veterans

    Science.gov (United States)

    ... of PTSD tripled over the course of the study. Sleep apnea was the most commonly diagnosed sleep disorder among the study participants. Sleep apnea, which causes brief pauses in breathing during ...

  20. 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.

  1. 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.

  2. Sleep deprivation: consequences for students.

    Science.gov (United States)

    Marhefka, Julie King

    2011-09-01

    During the adolescent years, a delayed pattern of the sleep-wake cycle occurs. Many parents and health care providers are not aware that once established, these poor sleep habits can continue into adulthood. Early school hours start a pattern of sleep loss that begins a cycle of daytime sleepiness, which may affect mood, behavior, and increase risk for accidents or injury. These sleep-deprived habits established in adolescence can often lead to problems during college years. Sleep hygiene can be initiated to help break the cycle, along with education and implementation of a strict regimen. Monitoring all adolescents and college-aged students for sleep insufficiency is imperative to improve both academic and emotional well-being. PMID:21846079

  3. 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 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...

  4. Sleep and Women’s Health

    OpenAIRE

    Nowakowski, Sara; Meers, Jessica; Heimbach, Erin

    2013-01-01

    Sex differences in sleep begin at a very early age and women report poorer sleep quality and have higher risk for insomnia than do men. Sleep may be affected by variation in reproductive hormones, stress, depression, aging, life/role transitions, and other factors. The menstrual cycle is associated with changes in circadian rhythms and sleep architecture. Menstruating women (even without significant menstrual-related complaints) often report poorer sleep quality and greater sleep disturbance ...

  5. 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...

  6. Sleep Disorders in Postmenopausal Women

    OpenAIRE

    Jehan, Shazia; Masters-Isarilov, Alina; Salifu, Idoko; Zizi, Ferdinand; Jean-Louis, Girardin; Pandi-Perumal, Seithikurippu R.; Gupta, Ravi; Brzezinski, Amnon; McFarlane, Samy I

    2015-01-01

    One of the core symptoms of the menopausal transition is sleep disturbance. Peri-menopausal women often complain of difficulties initiating and/or maintaining sleep with frequent nocturnal and early morning awakenings. Factors that may play a role in this type of insomnia include vasomotor symptoms, changing reproductive hormone levels, circadian rhythm abnormalities, mood disorders, coexistent medical conditions, and lifestyle. Other common sleep problems in this age group, such as obstructi...

  7. Sleep and Respiration in Microgravity

    Science.gov (United States)

    West, John B.; Elliott, Ann R.; Prisk, G. Kim; Paiva, Manuel

    2003-01-01

    Sleep is often reported to be of poor quality in microgravity, and studies on the ground have shown a strong relationship between sleep-disordered breathing and sleep disruption. During the 16-day Neurolab mission, we studied the influence of possible changes in respiratory function on sleep by performing comprehensive sleep recordings on the payload crew on four nights during the mission. In addition, we measured the changes in the ventilatory response to low oxygen and high carbon dioxide in the same subjects during the day, hypothesizing that changes in ventilatory control might affect respiration during sleep. Microgravity caused a large reduction in the ventilatory response to reduced oxygen. This is likely the result of an increase in blood pressure at the peripheral chemoreceptors in the neck that occurs when the normally present hydrostatic pressure gradient between the heart and upper body is abolished. This reduction was similar to that seen when the subjects were placed acutely in the supine position in one-G. In sharp contrast to low oxygen, the ventilatory response to elevated carbon dioxide was unaltered by microgravity or the supine position. Because of the similarities of the findings in microgravity and the supine position, it is unlikely that changes in ventilatory control alter respiration during sleep in microgravity. During sleep on the ground, there were a small number of apneas (cessation of breathing) and hypopneas (reduced breathing) in these normal subjects. During sleep in microgravity, there was a reduction in the number of apneas and hypopneas per hour compared to preflight. Obstructive apneas virtually disappeared in microgravity, suggesting that the removal of gravity prevents the collapse of upper airways during sleep. Arousals from sleep were reduced in microgravity compared to preflight, and virtually all of this reduction was as a result of a reduction in the number of arousals from apneas and hypopneas. We conclude that any sleep

  8. Does sleep improve memory organization?

    Directory of Open Access Journals (Sweden)

    Masashi eTakeuchi

    2014-04-01

    Full Text Available Sleep can integrate information into existing memory networks, look for common patterns and distill overarching rules, or simply stabilize and strengthen the memory exactly as it was learned. Recent research has shown that sleep facilitates abstraction of gist information as well as integration across multiple memories, insight into hidden solutions, and even the ability to make creative connections between distantly related ideas and concepts. To investigate the effect of sleep on memory organization, thirty-five normal volunteers were randomly assigned either to the sleep (n=17 or wake group (n=18. The sleep subjects performed the Japanese Verbal Learning Test (JVLT, a measure of learning and memory, three times in the evening, and slept. On the following morning (9 hours later, they were asked to recall the words on the list. The wake subjects took the same test in the morning, and were asked to recall the words in the same time interval as in the sleep group. The Semantic Clustering Ratio (SCR, divided by the total number of words recalled, was used as an index of memory organization. Our main interest was whether the sleep subjects elicit a greater increase in this measure from the third to the fourth assessments. Time-by-group interaction effect on SCR was not significant between the sleep group and wake group as a whole. Meanwhile, the change in the SCR between the third and fourth trials was negatively correlated with duration of nocturnal waking in the sleep group, but not other sleep indices. Based on this observation, further analysis was conducted for subjects in the sleep group who awoke nocturnally for less than 60 minutes for comparison with the wake group. A significant time-by-group interaction was noted; these good-sleepers showed a significantly greater improvement in the memory index compared with the wake subjects. These results provide the first suggestion that sleep may enhance memory organization, which requires further

  9. Sleep and circadian rhythms

    Science.gov (United States)

    Monk, Timothy H.

    1991-01-01

    Three interacting processes are involved in the preservation of circadian rhythms: (1) endogenous rhythm generation mechanisms, (2) entrainment mechanisms to keep these rhythms 'on track', and (3) exogenous masking processes stemming from changes in environment and bahavior. These processes, particularly the latter two, can be dramatically affected in individuals of advanced age and in space travelers, with a consequent disruption in sleep and daytime functioning. This paper presents results of a phase-shift experiment investigating the age-related effects of the exogeneous component of circadian rhythms in various physiological and psychological functions by comparing these functions in middle aged and old subjects. Dramatic differences were found between the two age groups in measures of sleep, mood, activation, and performance efficiency.

  10. 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

  11. Sleep and Learning

    Science.gov (United States)

    Margoliash, Daniel

    2010-03-01

    The neural basis of cognition represents a grand challenge problem involving multiple disciplines and approaches to the analysis of behavior. Song learning by juvenile songbirds such as zebra finches has proven to have considerable utility for exploring how behavior is represented at multiple levels of brain function. As classically described, young birds are exposed to a ``tutor'' (adult) song and commit that song to memory early in life, then engage in an extended period (weeks) of plastic singing as they slowly learn to match vocal output to the tutor song memory via auditory feedback. In recent years, the role of sleep in learning processes has been actively explored. Young birds isolated from adult songs, then suddenly given access to such songs at circa 40 days of age, show a sudden change in their singing behavior starting on the day following first exposure. Such birds sing songs that have less structure in the mornings than do the songs sung in the afternoons before or after that morning. This fluctuation is directly the result of sleep (not circadian rhythm), and the magnitude of fluctuation is positively correlated with the ultimate similarity to the tutor song. Examining spontaneous neuronal activity in certain brain structures during the night in sleeping adults shows ``replay'' of the patterns of activity the same neurons exhibit during daytime singing, and ``preplay'' of new patterns that will first be incorporated into daytime singing the following day. In experiments on juveniles, nighttime neuronal activity shows dramatic changes associated with song learning, even on the night after the first day of tutor song exposure (preceding changes in singing behavior). Offline processing, especially sleep, has been well documented to participate in memory consolidation in a very broad range of behaviors including in humans. Placing the bird song results in a theoretical framework thereby helps to inform a very broad range of phenomena.

  12. Primary sleep apnoea syndrome.

    OpenAIRE

    Chokroverty, S.; Sharp, J T

    1981-01-01

    Polygraphic study in 18 men with the sleep apnoea syndrome showed central, upper airway obstructive, and mixed apnoeas. Fifty per cent of the total apnoea time was central, 33% was obstructive, and 17% was mixed. Apnoeic episodes were accompanied by oxygen desaturation, relative bradycardia and hypotonia of orofacial muscles innervated by ponto-medullary neurons. During regular breathing these muscles revealed tonic and phasic inspiratory EMG activities. The data suggest that the primary slee...

  13. No ordinary sleep

    OpenAIRE

    Mockrin, Jessica F.

    2011-01-01

    No ordinary sleep includes nine works that combine oil painting with photographs printed on canvas. The painting and the photograph are not resolved into a continuous image but rather left with the seams exposed: painted figures floating in an uninhabitable, photographic space. The nine images depict the same two young men, nude and in close proximity to each other but rarely touching. These paintings raise questions about modes of reproduction, the use of the composite, fantasy, kitsch, desi...

  14. Sleep-related psychosis

    OpenAIRE

    Frase, Lukas; Sixt, Barbara; Nissen, Christoph

    2013-01-01

    We report the case of a 19-year-old male student with a Kleine-Levin syndrome who was referred to our sleep laboratory during an episode of hypersomnia, hypersexuality, cognitive impairment and bizarre behaviour. Owing to similar clinical symptoms, he had been misdiagnosed with schizophrenia. This had led to a placement in a facility for persons with chronic schizophrenia, antipsychotic pharmacotherapy for 4 years and side effects, including substantial weight gain and hypertension. After ces...

  15. Sleep and Stroke

    OpenAIRE

    M V Padma Srivastav

    2014-01-01

    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 ...

  16. Sleep without drugs

    OpenAIRE

    Giblin, M J; Clift, A. D.

    1983-01-01

    Disturbed sleep is a common problem, particularly among elderly people, and is usually treated with hypnotics. The side effects of longterm administration of hypnotic drugs are well known, but despite this there remains a substantial population of chronic users. These people can be helped to reduce their dependence on hypnotics through psychological techniques. A group of longterm users treated in this manner were shown to reduce their intake of hypnotics significantly more than a group of us...

  17. Sleep and stroke

    OpenAIRE

    Dib, Salim; Ramos, Alberto R.; Wallace, Douglas M; Rundek, Tatjana

    2012-01-01

    Obstructive Sleep-Disordered Breathing (OSDB) is an under-recognized risk factor for stroke. OSDB is associatedwith traditional vascular risk factors such as hypertension, obesity, and diabetes, and can influence the risk for stroke through direct and indirect mechanisms. Untreated OSDB may also influence rehabilitation efforts and functional outcome following a stroke, as well as the risk for stroke recurrence. Stroke risk is greatly reduced if the OSDB is adequately treated. Conversely, ...

  18. 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.

  19. 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.

  20. Sleep quality of professional firefighters

    Directory of Open Access Journals (Sweden)

    Ramin Mehrdad

    2013-01-01

    Full Text Available Background: Firefighting is a unique job with contradictious demands that expose firefighters to many well documented causal factors of sleep debt, but no studies in Iran and only a few worldwide studies have investigated their sleep quality while sleep problems may lead to catastrophes especially in critical service workers. The aim of this study is to evaluate sleep quality and its related factors among a sample of professional Iranian firefighters. Methods: Using simple random sampling method in a cross-sectional study, 427 personnel of fire and rescue service were invited. They completed the Persian version of Pittsburgh Sleep Quality Index (PSQI and a data collection sheet about their demographic and occupational features during an individual face to face interview in central office and firehouses throughout Tehran. Response rate was 88.7%. Results: The mean ± SD global PSQI score was 7.97 ± 3.77. Sleep latency was the component of PSQI with the greatest degree of abnormality. 69.9% of participants were poor sleepers. Interestingly, we found no significant differences between sleep quality of shift workers and non shift workers. Using multiple logistic regression analysis, only having another job, smoking and years of job experience were predictors of poor sleep. Conclusions: In comparison with adult population of Tehran, sleep quality deterioration is notably more common in Tehran firefighters which require health promotion interventions to prevent its serious adverse outcomes.

  1. Sleep apnea in childhood migraine

    OpenAIRE

    Bruni, Oliviero; Miano, Silvia; Galli, Federica; Verrillo, Elisabetta; Guidetti, Vincenzo

    2000-01-01

    In our previous study we found a high prevalence of disordered sleep breathing in migraine children vs. controls. Since no quantitative studies about sleep respiratory disorders have been carried out in migraine children, we performed a polysomnographic (PSG) study in 10 migraine patients (7 boys, 3 girls; mean age 8.11 years, range, 5.8–14.5) attending the Headache Center of our department, to evaluate the presence of sleep apnea. Mothers completed a headache diary and a sleep diary for at l...

  2. Sleep quality and sleep associated problems in female pharmacy students

    Directory of Open Access Journals (Sweden)

    Vivek Jain

    2013-01-01

    Full Text Available Background: Sleep is an essential element for adolescent mental and physical growth and development, but today′s young adolescents are deprived of this. Earlier studies in Europe and America showed pitiable sleep quality of young college students, which affect their academic growth. However, as per our literature search there is a lack of such studies in Indian context especially, within pharmacy education. Objective: The present study was designed to investigate the interrelation between the demographic characteristics, life-style, and academic progress with sleep quality and sleep problems along with daytime and nighttime habits in young female pharmacy students of India. Materials and Methods: Questionnaire on sleep and daytime habits (QS and DH was prepared. Our sample survey consists of 226 female pharmacy students of Banasthali University. QS and DH of multiple choice type, covered demographic characteristic (3 questions sleep and daytime habits (25 questions, life-style and academic progress (3 questions, and one question of course curriculum. Parameters were co-related by point scale method using the SPSS 16.0 software. Results: Data derived and analyze from survey illustrated that quality of sleep was as: Excellent - 20.4%, good - 38.5%, satisfactory - 35.8%, poor - 4%, and very poor - 1.3% of participants. Living condition (ρ=0.168, P =0.011, academic progress (ρ=0.151, P=0.023, leisure activity (ρ=0.133, P<0.05, and daytime naps (ρ=0.160, P=0.016 were significantly correlated with sleep quality. In addition, daytime sleepiness caused a significant problem for students and created a number of sleep disorders. Nevertheless, Sleep quality was not associated with age, body mass index, and coffee in the late evening. Conclusion: Study reported that sleep associated problems were common complaints in female pharmacy students.

  3. Sleep disorders in pregnancy

    Directory of Open Access Journals (Sweden)

    Lopes Eliane Aversa

    2004-01-01

    Full Text Available CONTEXT: The precise function of sleep in animals and human beings is still unknown, and any sort of physical, social or psychological variation may change the normal sleep-wake cycle. PURPOSE: This research aims is to determine the sleep disorders (SD for each of the three trimesters of the pregnancy comparing them to the pre-pregnancy state (PG. METHOD: SD were investigated in three hundred pregnant women 11- to 40-years-old through with a brief clinical interview based on directed questions. One hundred pregnant women were considered for each trimester. RESULTS: The rate of pregnant women with insomnia increased by 23% in the 2nd trimester (p< 0.005; the rate for excessive daytime sleepiness (EDS by 15% in the 1st trimester (p<0.003, 55% in the 2nd trimester (p<0.001 and by 14% in the 3rd trimester (p<0.002; the rate for mild sleepiness increased by 33% in the 2nd trimester (p<0.002 and by 48% in the 3rd trimester (p<0.001; the rate for specific awakenings increased by 63% in the 1st trimester, by 80% in the 2nd trimester and by 84% in the 3rd trimester (p<0.001. CONCLUSION: SD were more frequent during pregnancy comparatively to PG state, mostly at the expenses of EDS and specific awakenings.

  4. 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.

  5. Synthesis of novel guttiferone A derivatives: in-vitro evaluation toward Plasmodium falciparum, Trypanosoma brucei and Leishmania donovani.

    Science.gov (United States)

    Fromentin, Yann; Gaboriaud-Kolar, Nicolas; Lenta, Bruno Ndjakou; Wansi, Jean Duplex; Buisson, Didier; Mouray, Elisabeth; Grellier, Philippe; Loiseau, Philippe M; Lallemand, Marie-Christine; Michel, Sylvie

    2013-07-01

    The catechol pharmacomodulation of the natural product guttiferone A, isolated from the Symphonia globulifera tree, led to the semisynthesis of a collection of twenty derivatives. The ester and ether derivatives of guttiferone A were evaluated for their anti-plasmodial, trypanocidal and anti-leishmanial activities. Some compounds described below have shown potent antiparasitic activity against Plasmodium falciparum, Trypanosoma brucei and Leishmania donovani in a range from 1 to 5 μM. The evaluation of guttiferone A derivatives against VERO cells highlighted catechol modulations as an interesting tool to decrease the toxicity and keep the activity of this natural compound. The current study revealed new molecules as promising new antiparasitic drug candidates. PMID:23727538

  6. JBP2, a SWI2/SNF2-like protein, regulates de novo telomeric DNA glycosylation in bloodstream form Trypanosoma brucei.

    Science.gov (United States)

    Kieft, Rudo; Brand, Verena; Ekanayake, Dilrukshi K; Sweeney, Kate; DiPaolo, Courtney; Reznikoff, William S; Sabatini, Robert

    2007-11-01

    Synthesis of the modified thymine base, beta-d-glucosyl-hydroxymethyluracil or J, within telomeric DNA of Trypanosoma brucei correlates with the bloodstream form specific epigenetic silencing of telomeric variant surface glycoprotein genes involved in antigenic variation. In order to analyze the function of base J in the regulation of antigenic variation, we are characterizing the regulatory mechanism of J biosynthesis. We have recently proposed a model in which chromatin remodeling by a SWI2/SNF2-like protein (JBP2) regulates the developmental and de novo site-specific localization of J synthesis within bloodstream form trypanosome DNA. Consistent with this model, we now show that JBP2 (-/-) bloodstream form trypanosomes contain five-fold less base J and are unable to stimulate de novo J synthesis in newly generated telomeric arrays. PMID:17706299

  7. Differential expression of glycosomal and mitochondrial proteins in the two major life-cycle stages of Trypanosoma brucei.

    Science.gov (United States)

    Vertommen, Didier; Van Roy, Joris; Szikora, Jean-Pierre; Rider, Mark H; Michels, Paul A M; Opperdoes, Fred R

    2008-04-01

    Label-free semi-quantitative differential three-dimensional liquid chromatography coupled to mass spectrometry (3D-LC-MS/MS) was used to compare the glycosomal and mitochondrial proteomes of the bloodstream- and insect-form of Trypanosoma brucei. The abundance of glycosomal marker proteins identified in the two life-cycle stages corresponded well with the relative importance of biochemical pathways present in the glycosomes of the two stages and the peptide spectral count ratios of selected enzymes were in good agreement with published data about their enzymatic specific activities. This approach proved extremely useful for the generation of large scale proteomics data for the comparison of different life-cycle stages. Several proteins involved in oxidative stress protection, sugar-nucleotide synthesis, purine salvage, nucleotide-monophosphate formation and purine-nucleotide cycle were identified as glycosomal proteins. PMID:18242729

  8. 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...... and 140 days post-infection (dpi) respectively. Matched serum and CSF samples were obtained at regular intervals and immunospecific IgM, immunoglobulin G (IgG) and IL-10 were quantified by ELISA. RESULTS: There was no detectable immunospecific IgM and IgG in the CSF before 49 dpi. CSF IgM and Ig...... followed a pattern that mimics the progression of the disease and may present reliable and useful biomarkers of the disease stage. Due to rapid decline, serum IgM and IL-10 are, additionally, potential biomarkers of the success of chemotherapy....

  9. 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...

  10. The relationship between parent and child dysfunctional beliefs about sleep and child sleep

    OpenAIRE

    Ng, A S; Helen F Dodd; Gamble, A. L.; Hudson, J. L.

    2013-01-01

    Cognitive theories emphasise the role of dysfunctional beliefs about sleep in the development and maintenance of sleep-related problems (SRPs). The present research examines how parents' dysfunctional beliefs about children's sleep and child dysfunctional beliefs about sleep are related to each other and to children's subjective and objective sleep. Participants were 45 children aged 11 -12 years and their parents. Self-report measures of dysfunctional beliefs about sleep and child sleep were...

  11. 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.

  12. The multiple roles of cyclin E1 in controlling cell cycle progression and cellular morphology of Trypanosoma brucei.

    Science.gov (United States)

    Gourguechon, Stéphane; Savich, Jason M; Wang, Ching C

    2007-05-11

    Regulation of eukaryotic cell cycle progression requires sequential activation and inactivation of cyclin-dependent kinases. Previous RNA interference (RNAi) experiments in Trypanosoma brucei indicated that cyclin E1, cdc2-related kinase (CRK)1 and CRK2 are involved in regulating G1/S transition, whereas cyclin B2 and CRK3 play a pivotal role in controlling the G2/M checkpoint. To search for potential interactions between the other cyclins and CRKs that may not have been revealed by the RNAi assays, we used the yeast two-hybrid system and an in vitro glutathione-S-transferase pulldown assay and observed interactions between cyclin E1 and CRK1, CRK2 and CRK3. Cyclins E1-E4 are homologues of yeast Pho80 cyclin. But yeast complementation assays indicated that none of them possesses a Pho80-like function. Analysis of cyclin E1+CRK1 and cyclin E1+CRK2 double knockdowns in the procyclic form of T. brucei indicated that the cells were arrested more extensively in the G1 phase beyond the cumulative effect of individual knockdowns. But BrdU incorporation was impaired significantly only in cyclin E1+CRK1-depleted cells, whereas a higher percentage of cyclin E1+CRK2 knockdown cells assumed a grossly elongated posterior end morphology. A double knockdown of cyclin E1 and CRK3 arrested cells in G2/M much more efficiently than if only CRK3 was depleted. Taken together, these data suggest multiple functions of cyclin E1: it forms a complex with CRK1 in promoting G1/S phase transition; it forms a complex with CRK2 in controlling the posterior morphogenesis during G1/S transition; and it forms a complex with CRK3 in promoting passage across the G2/M checkpoint in the trypanosome. PMID:17376478

  13. 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.

  14. The spliceosomal snRNP core complex of Trypanosoma brucei: Cloning and functional analysis reveals seven Sm protein constituents

    Science.gov (United States)

    Palfi, Zsofia; Lücke, Stephan; Lahm, Hans-Werner; Lane, William S.; Kruft, Volker; Bragado-Nilsson, Elisabeth; Séraphin, Bertrand; Bindereif, Albrecht

    2000-01-01

    Each of the trypanosome small nuclear ribonucleoproteins (snRNPs) U2, U4/U6, and U5, as well as the spliced leader (SL) RNP, contains a core of common proteins, which we have previously identified. This core is unusual because it is not recognized by anti-Sm Abs and it associates with an Sm-related sequence in the trypanosome small nuclear RNAs (snRNAs). Using peptide sequences derived from affinity-purified U2 snRNP proteins, we have cloned cDNAs for five common proteins of 8.5, 10, 12.5, 14, and 15 kDa of Trypanosoma brucei and identified them as Sm proteins SmF (8.5 kDa), -E (10 kDa), -D1 (12.5 kDa), -G (14 kDa), and -D2 (15 kDa), respectively. Furthermore, we found the trypanosome SmB (T. brucei) and SmD3 (Trypanosoma cruzi) homologues through database searches, thus completing a set of seven canonical Sm proteins. Sequence comparisons of the trypanosome proteins revealed several deviations in highly conserved positions from the Sm consensus motif. We have identified a network of specific heterodimeric and -trimeric Sm protein interactions in vitro. These results are summarized in a model of the trypanosome Sm core, which argues for a strong conservation of the Sm particle structure. The conservation extends also to the functional level, because at least one trypanosome Sm protein, SmG, was able to specifically complement a corresponding mutation in yeast. PMID:10900267

  15. Sleep and Breathing at High Altitude.

    Science.gov (United States)

    Wickramasinghe, Himanshu; Anholm, James D.

    1999-01-01

    Sleep at high altitude is characterized by poor subjective quality, increased awakenings, frequent brief arousals, marked nocturnal hypoxemia, and periodic breathing. A change in sleep architecture with an increase in light sleep and decreasing slow-wave and REM sleep have been demonstrated. Periodic breathing with central apnea is almost universally seen amongst sojourners to high altitude, although it is far less common in long-standing high altitude dwellers. Hypobaric hypoxia in concert with periodic breathing appears to be the principal cause of sleep disruption at altitude. Increased sleep fragmentation accounts for the poor sleep quality and may account for some of the worsened daytime performance at high altitude. Hypoxic sleep disruption contributes to the symptoms of acute mountain sickness. Hypoxemia at high altitude is most severe during sleep. Acetazolamide improves sleep, AMS symptoms, and hypoxemia at high altitude. Low doses of a short acting benzodiazepine (temazepam) may also be useful in improving sleep in high altitude. PMID:11898114

  16. 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.

  17. 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.

  18. Sleep Disturbances in Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Cátia Alves Moreira

    2015-11-01

    Full Text Available Background: Bipolar disorder, characterized by episodes of mania, hypomania and depression is associated with sleep disturbances and circadian rhythm disruption. These changes have significant impact on quality of life and in the disease prognosis. Aims: Review of the main sleep disturbances observed in the bipolar disorder, their clinical impact and the hypothetical pathophysiological mechanisms involved. Methods: We conducted a non-systematic review of the literature in English through research in PubMed with the keywords “sleep disturbance”, “bipolar disorder”, “polysomnography”. Results and Conclusions: Complaints about sleep pattern changes may occur during any phase of the disease. These in clude frequent night-time awakenings, poor sleep quality, reduction of the total sleeping time and decreased latency and increased density of REM sleep. The treatment of the sleep disturbances observed in bipolar disorder should be considered a priority, since it prevents symptoms recurrence and facilitate the socio-professional integration, thus providing greater success in patient’s rehabilitation and quality of life.

  19. 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.

  20. Sleep Tips for Sjogren's Patients

    Science.gov (United States)

    ... secure, dark, and quiet. Try to maintain good “sleep hygiene:” Get out of bed at the same time nearly every morning (including weekends) and into bed with lights out at roughly the same time at night. Use the bedroom for sleep and sex: no TV, no “homework,” no arguments, ...

  1. 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…

  2. 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....

  3. Melatonin use in sleep disorders

    OpenAIRE

    Chung, KF

    1997-01-01

    Melatonin is a widely publicized 'magical drug'. Claims of its use include regulation of sleep, circadian rhythm, mood, immune system and reproduction, anti-aging, protection against cancer, and treatment of AIDS. This article reviews the evidence of its use in sleep disorders. Its possible indications and adverse effects are discussed.

  4. How sleep activates epileptic networks?

    Science.gov (United States)

    Halász, Peter

    2013-01-01

    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.

  5. Characterization of 2,4-Diamino-6-oxo-1,6-dihydropyrimidin-5-yl Ureido Based Inhibitors of Trypanosoma brucei FolD and Testing for Antiparasitic Activity.

    Science.gov (United States)

    Eadsforth, Thomas C; Pinto, Andrea; Luciani, Rosaria; Tamborini, Lucia; Cullia, Gregorio; De Micheli, Carlo; Marinelli, Luciana; Cosconati, Sandro; Novellino, Ettore; Lo Presti, Leonardo; Cordeiro da Silva, Anabela; Conti, Paola; Hunter, William N; Costi, Maria P

    2015-10-22

    The bifunctional enzyme N(5),N(10)-methylenetetrahydrofolate dehydrogenase/cyclo hydrolase (FolD) is essential for growth in Trypanosomatidae. We sought to develop inhibitors of Trypanosoma brucei FolD (TbFolD) as potential antiparasitic agents. Compound 2 was synthesized, and the molecular structure was unequivocally assigned through X-ray crystallography of the intermediate compound 3. Compound 2 showed an IC50 of 2.2 μM, against TbFolD and displayed antiparasitic activity against T. brucei (IC50 49 μM). Using compound 2, we were able to obtain the first X-ray structure of TbFolD in the presence of NADP(+) and the inhibitor, which then guided the rational design of a new series of potent TbFolD inhibitors. PMID:26322631

  6. Pathophysiology of central sleep apneas.

    Science.gov (United States)

    Hernandez, Adam B; Patil, Susheel P

    2016-05-01

    The transition from wake to sleep is accompanied by a host of physiologic changes, which result in major alterations in respiratory control and may result in sleep-related breathing disorders. The central sleep apneas are a group of sleep-related breathing disorders that are characterized by recurrent episodes of airflow reduction or cessation due to a temporary reduction or absence of central respiratory drive. The fundamental hallmark of central sleep apnea (CSA) disorders is the presence of ventilatory control instability; however, additional mechanisms play a role in one or more specific manifestations of CSA. CSA may manifest during conditions of eucapnia/hypocapnia or chronic hypercapnia, which is a useful clinical classification that lends understanding to the underlying pathophysiology and potential therapies. In this review, an overview of normal breathing physiology is provided, followed by a discussion of pathophysiologic mechanisms that promote CSA and the mechanisms that are specific to different manifestations of CSA. PMID:26782104

  7. Sleep in intensive care unit

    DEFF Research Database (Denmark)

    Boyko, Yuliya; Jennum, Poul; Nikolic, Miki;

    2016-01-01

    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...

  8. 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…

  9. 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.

  10. 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.

  11. Sleep in obese patients

    OpenAIRE

    Natalya Victorova Strueva; Galina Afanas'evna Melnichenko; Mikhail Gur'evich Poluektov; Larisa Victorovna Savel'eva; Gul'nara Victorovna Katsiya; Nikolay Petrovich Goncharov

    2014-01-01

    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 circumf...

  12. Sleeps in Oysters: Lo!

    OpenAIRE

    Busby, Lisa; Harries, John

    2011-01-01

    A 12 track, 45 minute album of original recorded works released under the project name 'Sleeps in Oysters'. Lo! was released in a glossy card gatefold sleeve with each standard edition accompanied by a hand-illustrated insert depicting each of the 12 animal masks featured in the album photography as a cross stitch chart. 50 hand numbered special edition packs were available each with one of the 12 animal masks featured on the sleeve, and a kit consisting of threads, fabric and thimble to enab...

  13. 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…

  14. Sleep Problems in Asthma and COPD

    Science.gov (United States)

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

  15. Sleep: The E-ZZZ Intervention

    Science.gov (United States)

    Bergin, Christi A.; Bergin, David A.

    2009-01-01

    Research has shown that students who do not get enough sleep are more likely to misbehave in school and have lower academic achievement than their peers with healthy sleeping habits. In this article, Christi A. Bergin and David A. Bergin share research into students' sleep habits and conclude that helping students get adequate sleep has potential…

  16. 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

  17. Find a Sleep Center Near You

    Science.gov (United States)

    ... Sleep Insomnia Overview & Facts Symptoms & Causes Diagnosis & Self Tests Treatment Sleep Apnea Overview & Facts Symptoms & Risk Factors Self-Tests ... Snoring Overview and Facts Causes and Symptoms Self Tests & Diagnosis Treatments In-Lab Sleep Study Overview Preparing for a Sleep Study Testing ...

  18. Sleep and Rest Requirements: Physiological Considerations

    Science.gov (United States)

    Neri, David F.; Rosekind, Mark R. (Technical Monitor)

    1997-01-01

    Sleep is a vital physiological need which must be met to insure optimal functioning. A single night of significantly shortened sleep negatively impacts performance, alertness, and mood. Restricted sleep studies have shown that even a relatively small amount of sleep loss over several consecutive days can be additive and result in a cumulative sleep debt with similar detrimental effects. Compounding the problem of sleep loss in the operational environment is the poor correlation between subjective reports of sleepiness and objective measures of physiological sleep need. Some of the factors determining how sleepy an individual is at a given point in time are: (1) individual characteristics (e.g., amount of prior sleep and wakefulness, circadian phase, age), (2) environmental conditions (e.g., noise, temperature, amount of social interaction), and (3) task variables (e.g., signal rate, workload). Although sleep need can be masked with medications, the only way to reduce it is with sleep itself. The timing of the sleep period can affect sleep duration and quality and thus its restorative strength. The data are clear that increasing sleep time results in improved alertness. This paper will briefly review the scientific findings on sleep need, the effects of sleep loss, napping strategies, and the implications of incorporating physiologically sound sleep and rest strategies into the operational aviation environment.

  19. Sleep education in college: a preliminary study.

    Science.gov (United States)

    Tsai, Ling-Ling; Li, Sheng-Ping

    2004-12-01

    In this study we evaluated the effect of a two-credit (100 min./week) "Sleep Management" course on the sleep patterns of college students as the course progressed over an 18-wk. semester. Curricular activity included lectures, group discussions, and practice of self-evaluation of sleep. Instead of giving the students the whole list of sleep hygiene at the outset of the course, each concept of sleep hygiene was introduced and discussed under related lecture topics. A total of 241 students (131 men and 110 women) took the course and kept 7-day sleep logs three times. Concurrently, sleep-log data were collected from 65 students (32 men and 33 women) who were not taking the course. Both groups showed similar varieties of academic backgrounds and characteristics of sleep patterns at the beginning. Similarly, their sleep patterns, namely, rise time, nighttime awakenings, time asleep, time in bed, sleep efficiency, and rise time regularity, changed over the semester. Women in both groups had more nighttime awakenings. In contrast, sleep quality was progressively better for the group in the course but not for the control group. Only women in the course decreased their nap time in the second and third months. Thus, the course of "Sleep Management" only had a mild and limited effect on sleep patterns. The course content needs refinement to maximize influence on students' sleep patterns and habits, particularly, on reduction of insufficient sleep and daytime sleepiness which are the highest ranking sleep problems among college students. PMID:15648478

  20. 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