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https://www.readbyqxmd.com/read/28642005/expression-purification-and-crystallization-of-type-1-isocitrate-dehydrogenase-from-trypanosoma-brucei
#1
Xinying Wang, Daniel Ken Inaoka, Tomoo Shiba, Emmanuel Oluwadare Balogun, Stefan Allmann, Yoh-Ichi Watanabe, Michael Boshart, Kiyoshi Kita, Shigeharu Harada
Isocitrate dehydrogenases (IDHs) are metabolic enzymes that catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate. Depending on the electron acceptor and subcellular localization, these enzymes are classified as NADP(+)-dependent IDH1 in the cytosol or peroxisomes, NADP(+)-dependent IDH2 and NAD(+)-dependent IDH3 in mitochondria. Trypanosoma brucei is a protozoan parasite that causes African sleeping sickness in humans and Nagana disease in animals. Here, for the first time, a putative glycosomal T...
June 19, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28637278/functional-and-structural-analysis-of-at-specific-minor-groove-binders-that-disrupt-dna-protein-interactions-and-cause-disintegration-of-the-trypanosoma-brucei-kinetoplast
#2
Cinthia R Millan, Francisco J Acosta-Reyes, Laura Lagartera, Godwin U Ebiloma, Leandro Lemgruber, J Jonathan Nué Martínez, Núria Saperas, Christophe Dardonville, Harry P de Koning, J Lourdes Campos
Trypanosoma brucei, the causative agent of sleeping sickness (Human African Trypanosomiasis, HAT), contains a kinetoplast with the mitochondrial DNA (kDNA), comprising of >70% AT base pairs. This has prompted studies of drugs interacting with AT-rich DNA, such as the N-phenylbenzamide bis(2-aminoimidazoline) derivatives 1 [4-((4,5-dihydro-1H-imidazol-2-yl)amino)-N-(4-((4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)benzamide dihydrochloride] and 2 [N-(3-chloro-4-((4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)-4-((4,5-dihydro-1H-imidazol-2-yl)amino)benzamide] as potential drugs for HAT...
June 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28636879/delineating-neuroinflammation-parasite-cns-invasion-and-blood-brain-barrier-dysfunction-in-an-experimental-murine-model-of-human-african-trypanosomiasis
#3
Jean Rodgers, Barbara Bradley, Peter G E Kennedy
Although Trypanosoma brucei spp. was first detected by Aldo Castellani in CSF samples taken from sleeping sickness patients over a century ago there is still a great deal of debate surrounding the timing, route and effects of transmigration of the parasite from the blood to the CNS. In this investigation, we have applied contrast-enhance magnetic resonance imaging (MRI) to study the effects of trypanosome infection on the blood-brain barrier (BBB) in the well-established GVR35 mouse model of sleeping sickness...
June 18, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28635658/asperentin-b-a-new-inhibitor-of-the-protein-tyrosine-phosphatase-1b
#4
Jutta Wiese, Hülya Aldemir, Rolf Schmaljohann, Tobias A M Gulder, Johannes F Imhoff
In the frame of studies on secondary metabolites produced by fungi from deep-sea environments we have investigated inhibitors of enzymes playing key roles in signaling cascades of biochemical pathways relevant for the treatment of diseases. Here we report on a new inhibitor of the human protein tyrosine phosphatase 1B (PTP1B), a target in the signaling pathway of insulin. A new asperentin analog is produced by an Aspergillussydowii strain isolated from the sediment of the deep Mediterranean Sea. Asperentin B (1) contains an additional phenolic hydroxy function at C-6 and exhibits an IC50 value against PTP1B of 2 μM in vitro, which is six times stronger than the positive control, suramin...
June 21, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28623292/structural-and-biochemical-characterization-of-poly-adp-ribose-polymerase-from-trypanosoma-brucei
#5
Teemu Haikarainen, Mariana Schlesinger, Ezeogo Obaji, Silvia H Fernández Villamil, Lari Lehtiö
Trypanosoma brucei is a unicellular parasite responsible for African trypanosomiasis or sleeping sickness. It contains a single PARP enzyme opposed to many higher eukaryotes, which have numerous PARPs. PARPs are responsible for a post-translational modification, ADP-ribosylation, regulating a multitude of cellular events. T. brucei PARP, like human PARPs-1-3, is activated by DNA binding and it potentially functions in DNA repair processes. Here we characterized activation requirements, structure and subcellular localization of T...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28620452/metabolic-reprogramming-during-the-trypanosoma-brucei-life-cycle
#6
REVIEW
Terry K Smith, Frédéric Bringaud, Derek P Nolan, Luisa M Figueiredo
Cellular metabolic activity is a highly complex, dynamic, regulated process that is influenced by numerous factors, including extracellular environmental signals, nutrient availability and the physiological and developmental status of the cell. The causative agent of sleeping sickness, Trypanosoma brucei, is an exclusively extracellular protozoan parasite that encounters very different extracellular environments during its life cycle within the mammalian host and tsetse fly insect vector. In order to meet these challenges, there are significant alterations in the major energetic and metabolic pathways of these highly adaptable parasites...
2017: F1000Research
https://www.readbyqxmd.com/read/28609481/the-ubiquitin-conjugating-enzyme-cdc34-is-essential-for-cytokinesis-in-contrast-to-putative-subunits-of-a-scf-complex-in-trypanosoma-brucei
#7
Federico Rojas, Joanna Koszela, Jacqueline Búa, Briardo Llorente, Richard Burchmore, Manfred Auer, Jeremy C Mottram, María Teresa Téllez-Iñón
The ubiquitin-proteasome system is a post-translational regulatory pathway for controlling protein stability and activity that underlies many fundamental cellular processes, including cell cycle progression. Target proteins are tagged with ubiquitin molecules through the action of an enzymatic cascade composed of E1 ubiquitin activating enzymes, E2 ubiquitin conjugating enzymes, and E3 ubiquitin ligases. One of the E3 ligases known to be responsible for the ubiquitination of cell cycle regulators in eukaryotes is the SKP1-CUL1-F-box complex (SCFC)...
June 13, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28605986/perceived-stress-disturbed-sleep-and-cognitive-impairments-in-patients-with-work-related-stress-complaints-a-longitudinal-study
#8
Anita Eskildsen, Hanne Nørr Fentz, Lars Peter Andersen, Anders Degn Pedersen, Simon Bang Kristensen, Johan Hviid Andersen
Patients on sick leave due to work-related stress often present with cognitive impairments as well as sleep disturbances. The aim of this longitudinal study was to examine the role of perceived stress and sleep disturbances in the longitudinal development in cognitive impairments in a group of patients with prolonged work-related stress (N = 60) during a period of 12 months following initial professional care-seeking. Objective cognitive impairments (neuropsychological tests) were measured on two occasions - at initial professional care-seeking and at 12-month follow-up...
June 12, 2017: Stress: the International Journal on the Biology of Stress
https://www.readbyqxmd.com/read/28596486/experimental-african-trypanosome-infection-suppresses-the-development-of-multiple-myeloma-in-mice-by-inducing-intrinsic-apoptosis-of-malignant-plasma-cells
#9
Nathan De Beule, Eline Menu, Mathieu Jm Bertrand, Mérédis Favreau, Elke De Bruyne, Ken Maes, Kim De Veirman, Magdalena Radwanska, Afshin Samali, Stefan Magez, Karin Vanderkerken, Carl De Trez
Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells in the bone marrow (BM). Recently, several studies have highlighted the role of pathogens in either promoting or dampening malignancies of unrelated origin. Trypanosoma brucei is an extracellular protozoan parasite which causes sleeping sickness. Our group has previously demonstrated that trypanosome infection affects effector plasma B cells. Therefore, we hypothesized that T. brucei infection could have an impact on MM development...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28586543/acute-fatigue-predicts-sickness-absence-in-the-workplace-a-1-year-retrospective-cohort-study-in-pediatric-nurses
#10
Knar Sagherian, George J Unick, Shijun Zhu, Debra Derickson, Pamela S Hinds, Jeanne Geiger-Brown
AIMS: To examine the relationship between fatigue and sickness absence in nurses from a pediatric hospital over 12 months of follow-up. A secondary aim was to identify other work and personal factors that predict sickness absence. BACKGROUND: Sickness absence is often related to worker-fatigue, yet few studies have explored this relationship in nurses despite documented high fatigue levels. DESIGN: The study used retrospective cohort design...
June 6, 2017: Journal of Advanced Nursing
https://www.readbyqxmd.com/read/28586253/characterization-of-recombinant-trypanosoma-brucei-gambiense-translationally-controlled-tumor-protein-rtbgtctp-and-its-interaction-with-glossina-midgut-bacteria
#11
Géraldine Bossard, Manon Bartoli, Marie-Laure Fardeau, Philippe Hozmuller, Bernard Ollivier, Anne Geiger
In humans, sleeping sickness (i.e. Human African Trypanosomiasis) is caused by the protozoan parasites Trypanosoma brucei gambiense (Tbg) in West and Central Africa, and T. b. rhodesiense in East Africa. We previously showed in vitro that Tbg is able to excrete/secrete a large number of proteins, including Translationally Controlled Tumour Protein (TCTP). Moreover, the tctp gene was previously described to be expressed in Tbg-infected flies. Aside from its involvement in diverse cellular processes, we have investigated a possible alternative role within the interactions occurring between the trypanosome parasite, its tsetse fly vector, and the associated midgut bacteria...
June 6, 2017: Gut Microbes
https://www.readbyqxmd.com/read/28578742/applicability-of-plant-based-products-in-the-treatment-of-trypanosoma-cruzi-and-trypanosoma-brucei-infections-a-systematic-review-of-preclinical-in-vivo-evidence
#12
Rodrigo M Pereira, Glícia M Z Greco, Andreia M Moreira, Pablo F Chagas, Ivo S Caldas, Reggiani V Gonçalves, Rômulo D Novaes
Chagas disease and sleeping sickness are neglected tropical diseases closely related to poverty, for which the development of plant-derived treatments has not been a promising prospect. Thus, we systematicaly review the preclinical in vivo evidence on the applicability of plant-based products in the treatment of Trypanosoma cruzi and Trypanosoma brucei infections. Characteristics such as disease models, treatments, toxicological safety and methodological bias were analysed. We recovered 66 full text articles from 16 countries investigating 91 plant species...
June 5, 2017: Parasitology
https://www.readbyqxmd.com/read/28575287/an-essential-domain-of-an-early-diverged-rna-polymerase-ii-functions-to-accurately-decode-a-primitive-chromatin-landscape
#13
Anish Das, Mahrukh Banday, Michael A Fisher, Yun-Juan Chang, Jeffrey Rosenfeld, Vivian Bellofatto
A unique feature of RNA polymerase II (RNA pol II) is its long C-terminal extension, called the carboxy-terminal domain (CTD). The well-studied eukaryotes possess a tandemly repeated 7-amino-acid sequence, called the canonical CTD, which orchestrates various steps in mRNA synthesis. Many eukaryotes possess a CTD devoid of repeats, appropriately called a non-canonical CTD, which performs completely unknown functions. Trypanosoma brucei, the etiologic agent of African Sleeping Sickness, deploys an RNA pol II that contains a non-canonical CTD to accomplish an unusual transcriptional program; all protein-coding genes are transcribed as part of a polygenic precursor mRNA (pre-mRNA) that is initiated within a several-kilobase-long region, called the transcription start site (TSS), which is upstream of the first protein-coding gene in the polygenic array...
May 26, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28573456/backbone-nmr-assignments-of-tryparedoxin-the-central-protein-in-the-hydroperoxide-detoxification-cascade-of-african-trypanosomes-in-the-oxidized-and-reduced-form
#14
Annika Wagner, Erika Diehl, R Luise Krauth-Siegel, Ute A Hellmich
Tryparedoxin (Tpx) is a pivotal protein in the redox-metabolism of trypanosomatid parasites. Tpx has previously been identified as a potential target for drug development in the fight against human African sleeping sickness caused by Trypanosoma brucei. Tpx belongs to the thioredoxin superfamily and acts as an oxidoreductase in the parasite's cytoplasm. It contains a WCPPC active site motif, which enables the protein to undergo thiol-disulfide exchange. To promote future protein-drug interaction analyses, we report the (1)H, (13)C and (15)N backbone chemical shift assignments for both the oxidized and reduced states of Tpx...
June 1, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28571553/parasite-polyamines-as-pharmaceutical-targets
#15
Sigrid Roberts, Buddy Ullman
There is an urgent need for the identification and validation of new therapeutic targets in protozoan parasites because currently available drugs are limited in number and usefulness, and no vaccines are available. The discovery that alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, is an efficacious treatment for African Sleeping Sickness caused by the protozoan parasite Trypanosoma brucei, has validated the polyamine pathway as a target in protozoan parasites. Polyamines are ubiquitous organic cations that play critical roles in key cellular processes such as growth, differentiation, and macromolecular biosynthesis...
May 31, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28552794/front-line-glioblastoma-chemotherapeutic-temozolomide-is-toxic-to-trypanosoma-brucei-and-potently-enhances-melarsoprol-and-eflornithine
#16
Dietmar Steverding, Stuart A Rushworth
Sleeping sickness is an infectious disease that is caused by the protozoan parasite Trypanosoma brucei. The second stage of the disease is characterised by the parasites entering the brain. It is therefore important that sleeping sickness therapies are able to cross the blood-brain barrier. At present, only three medications for chemotherapy of the second stage of the disease are available. As these trypanocides have serious side effects and are difficult to administer, new and safe anti-trypanosomal brain-penetrating drugs are needed...
July 2017: Experimental Parasitology
https://www.readbyqxmd.com/read/28533143/drugs-in-space-pharmacokinetics-and-pharmacodynamics-in-astronauts
#17
REVIEW
Johannes Kast, Yichao Yu, Christoph N Seubert, Virginia E Wotring, Hartmut Derendorf
Space agencies are working intensely to push the current boundaries of human spaceflight by sending astronauts deeper into space than ever before, including missions to Mars and asteroids. Spaceflight alters human physiology due to fluid shifts, muscle and bone loss, immune system dysregulation, and changes in the gastrointestinal tract and metabolic enzymes. These alterations may change the pharmacokinetics and/or pharmacodynamics of medications used by astronauts and subsequently might impact drug efficacy and safety...
May 19, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28530462/using-yoga-nidra-to-improve-stress-in-psychiatric-nurses-in-a-pilot-study
#18
Roberta Anderson, Kristine Mammen, Padmini Paul, Allisyn Pletch, Kathleen Pulia
Given today's hurried and stressful heathcare system, nurses need mechanisms to take care of themselves, promote their own wellness, and build resilience in managing sick patients. Yoga is one such mechanism; it can decrease anxiety and improve sleep and quality of life. In this pilot study, nine nurses participated in 6 weekly sessions of yoga nidra. Measures of sleep, stress, and muscle fatigue were obtained to determine whether yoga had a positive impact upon quality of life and stress. Although based on a small sample of nurses, results indicated positive findings for both perceived stress level and muscle fatigue...
June 2017: Journal of Alternative and Complementary Medicine: Research on Paradigm, Practice, and Policy
https://www.readbyqxmd.com/read/28522152/anti-trypanosomal-activity-of-cationic-n-heterocyclic-carbene-gold-i-complexes
#19
Isabel Winter, Julia Lockhauserbäumer, Gertrud Lallinger-Kube, Rainer Schobert, Klaus Ersfeld, Bernhard Biersack
Two gold(I) N-heterocyclic carbene complexes 1a and 1b were tested for their anti-trypanosomal activity against Trypanosoma brucei parasites. Both gold compounds exhibited excellent anti-trypanosomal activity (IC50=0.9-3.0nM). The effects of the gold complexes 1a and 1b on the T. b. brucei cytoskeleton were evaluated. Rapid detachment of the flagellum from the cell body occurred after treatment with the gold complexes. In addition, a quick and complete degeneration of the parasitic cytoskeleton was induced by the gold complexes, only the microtubules of the detached flagellum remained intact...
May 15, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28456523/the-canonical-poly-a-polymerase-pap1-polyadenylates-non-coding-rnas-and-is-essential-for-snorna-biogenesis-in-trypanosoma-brucei
#20
Vaibhav Chikne, Sachin Kumar Gupta, Tirza Doniger, Shanmugha Rajan K, Smadar Cohen-Chalamish, Hiba Waldman Ben-Asher, Liat Kolet, Nasreen Hag Yahia, Ron Unger, Elisabetta Ullu, Nikolay G Kolev, Christian Tschudi, Shulamit Michaeli
The parasite Trypanosoma brucei is the causative agent of African sleeping sickness and is known for its unique RNA processing mechanisms that are common to all the kinetoplastidea including Leishmania and Trypanosoma cruzi. Trypanosomes possess two canonical RNA poly (A) polymerases (PAPs) termed PAP1 and PAP2. PAP1 is encoded by one of the only two genes harboring cis-spliced introns in this organism, and its function is currently unknown. In trypanosomes, all mRNAs, and non-coding RNAs such as small nucleolar RNAs (snoRNAs) and long non-coding RNAs (lncRNAs), undergo trans-splicing and polyadenylation...
April 26, 2017: Journal of Molecular Biology
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