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SECTION B -ABSTRACTS (continued)

7. EXPERIMENTAL TRYPANOSOMIASIS

(a) DIAGNOSTICS

13353 Cox, A., Tilley, A., McOdimba, F., Fyfe, J., Eisler, M., Hide, G. & Welburn, S., 2005. A PCR based assay for detection and differentiation of African trypanosome species in blood. Experimental Parasitology , 111 (1): 24–29.

Welburn: Centre for Tropical Veterinary Medicine, Royal (Dick) School of Veterinary Medicine, University of Edinburgh, Easter Bush, Roslin, Midlothian EH25 9RG, UK.

Direct PCR analysis of trypanosome infected blood samples in the quantities required for large scale epidemiological study has always been problematic. Current methods for identifying and differentiating trypanosomes typically require several species-specific reactions, many of which rely on mouse passaged samples to obtain quality concentrated genomic DNA. As a consequence important epidemiological information may be lost during the sample preparation stage. Here, we report a PCR methodology that reduces processing and improves on the sensitivity of present screening methods. The PCR technique targets the gene encoding the small ribosomal subunit in order to identify and differentiate all clinically important African trypanosome species and some subspecies. The method is more economical, simple, and sensitive than current screening methods, and yields more detailed information, thereby making it a viable tool for large-scale epidemiological studies.

13354 Gonzalez, L.E., Garcia, J.A., Nunez, C., Perrone, T.M., Gonzalez-Baradat, B., Gonzatti, M. & Reyna-Bello, A., 2005. Trypanosoma vivax : A novel method for purification from experimentally infected sheep blood. Experimental Parasitology , 111 (2): 126–129.

Reyna-Bello: Universidad Simón Rodríguez-IDECYT, Laboratorio de Inmunología, Caracas, Venezuela.

Trypanosoma vivax is the principal aetiological agent of bovine trypanosomosis, a widely disseminated disease in tropical and subtropical regions. Here, we present a simple and reproducible method for the purification of T. vivax from experimentally infected and immunosuppressed sheep, using an isopycnic Percoll gradient, followed by DEAE-cellulose chromatography, with an estimated yield of 11–15 percent. This method could be used for the purification of T. vivax geographical isolates from various locations and from different natural hosts.

(b) PATHOLOGY AND IMMUNOLOGY

13355 Abenga, J.N., David, K.M., Ezebuiro, C.O.G., Samdi, S. & Fajinmi, A.O., 2004. Leucocyte and thrombocyte changes in young dogs infected with Trypanosoma congolense . Journal of Protozoology Research , 14 (1–2): 8–15.

Abenga: Pathology, Epidemiology and Statistics Division Nigerian Institute for Trypanosomiasis Research, P.M.B. 2077, Kaduna, Nigeria.

Studies were undertaken to determine the effect of infection with Trypanosoma congolense on the leucocyte and thrombocyte values of six local puppies. The puppies were of mixed sexes and seven weeks old. Although the puppies became parasitaemic 6 to 7 days post infection (PI), the effect on leucocyte counts were mild as significant leucopenia characterised by neutropenia, ensinopenia, and lymphopenia (P≤0.05) did not occur until the last four weeks of the 8 week observation period. Infection had more effects on thrombocyte counts as thrombocytopenia occurred from week one PI. The low impact of infection with T. congolense on the leucocyte values of infected puppies was attributable to trypanotolerance in the local breed of dogs and low antigenicity of the strain of T. congolense used. It is concluded that the ability to resist the development of anaemia may not be the only haematological evidence of trypanotolerance in animals and that further research is needed to determine the true trypanotolerance status of breeds of local dogs in Nigeria and other parts of the West African subregion.

13356 Abenga, J.N., Ezebuiro, C.O., David, K., Fajinmi, A.O. & Samdi, S., 2005. Studies on anaemia in Nigerian local puppies infected with Trypanosoma congolense . Veterinarski Arhiv , 75 (2): 165–174.

Abenga: Pathology, Epidemiology and Statistics Division, Nigerian Institute for Trypanosomiasis Research, Private Mail Bag, 2077 Kaduna, Nigeria.

Investigation into the effect of infection with Trypanosoma congolense on the haematology of growing Nigerian local dogs was undertaken using six puppies infected with 1×106of the parasites. Infection resulted in mild anaemia characterized by a slight drop in the packed cell volume (PCV), haemoglobin (Hb) and red blood cells (RBC) counts which did not occur until the second half of the eight-week observation period. The anaemia was macrocytic normochromic. The mild decrease in the overall erythrocyte values of T. congolense-infected young dogs was attributable to trypanotolerance in the local breed of dog. However, the infected group did not attain full erythrocyte values as in the control group, suggesting that similar changes occurring in infected young animals contribute to retarded growth associated with trypanosome infections.

13357 Ajuwape, A.T.P., Adetosoye, A.I., Ikheloa, J.O., Alaka, O.O., Taiwo, V.O., Talabi, O.A., Otesile, E.B. & Ojo, M.O., 2004. Pathogenicity of Mycoplasma capricolum subspecies capricolum for cattle immunosuppressed with Trypanosoma congolense . Israel Journal of Veterinary Medicine , 59 (4): 73–77.

Ajuwape: Department of Veterinary Microbiology and Parasitology, University of Ibadan, Ibadan, Nigeria.

The pathogenicity of Mycoplasma capricolum subspecies capricolum in Red Bororo (RB) bull calves was investigated. Two calves infected with 4.21×106 cells of Trypanosoma congolense and later inoculated endobronchially with 1.6×109 CFU/ml of M. capricolum subspecies capricolum (Tc/Mcc) died 38.0±1.4 days post infection (pi) presenting fibrinous interstitial pneumonia and severe lymphoid depletion in spleen and lymph nodes, while another set of two calves was infected with Trypanosoma congolense (Tc) only. The mean PCV values (mPCV) of each of the four Tc-infected RB calves (21.7±2.4 percent, 25.5±2.5 percent, 23.3±3.9 percent and 23.3±2.4 percent) were significantly lower than that of the control (31.1±1.7 percent). The mean rectal temperature (mRT) of each of the four calves (39.6±0.8 degrees C, 40.0±0.5 degrees C, 37.9±0.5 degrees C and 38.1±0.2 degrees C) with Tc and Mcc or Tc infections was significantly higher than that of the control (38.2±0.5 degrees C). In these experimental infections, necropsy examinations revealed oedema, congestion, consolidation and marbling of the lungs. Histopathological changes observed were inter alia thickening of the interlobular septae by fibrin and showers of lymphocytes. The spleen showed lymphoid necrosis and haemosiderosis in the red pulp. Mycoplasma capricolum subspecies capricolum was recovered from the lungs, lymph nodes, kidneys, spleen and liver of the dead calves. The Trypanosoma congolense infection induced a state of immunosuppression. In Africa, where cattle are herded along with sheep and goats, this study revealed that Mycoplasma capricolum subsp. capricolum can indeed cause CBPPlike lesions that may be indistinguishable from CBPP caused by bovine mycoplasmas. It is therefore suggested that thorough laboratory investigation should be carried out along with post mortem examination of suspected CBPP cases to identify the specific Mycoplasma species involved. Efforts should be made to immunize cattle, sheep and goats against M. capricolum subsp. capricolum .

13358 Berge, B., Chevrier, C., Blanc, A., Rehailia, M., Buguet, A. & Bourdon, L., 2005. Disruptions of ultradian and circadian organization of core temperature in a rat model of African trypanosomiasis using periodogram techniques on detrended data. Chronobiology International , 22 (2): 237–251.

Blanc: Laboratoire de Biologie Animale et Appliquée, 23 Rue Docteur Paul Michelon, F-42023 St Etienne, Cedex 2, France.

Periodogram techniques on detrended data were used to determine the effect of Trypanosoma brucei brucei infection on the distribution of the core temperature of rats and on the expression of temperature rhythms. In such an animal model, sudden episodic hypothermic bouts are described. These episodes of hypothermia are used here as marks for the purpose of performing time-based comparisons on temperature organization. The experiment was conducted on ten infected and three control (non-infected) Sprague-Dawley rats reared under a 24 h light-dark cycle. Core temperature was recorded continuously throughout the experiment, until the animals' death. Temperature distributions, analyzed longitudinally for the full duration of the experiment, exhibited a progressive shift from a bimodal to a unimodal pattern, suggesting a weakening of the day/night core temperature differences. After hypothermic events, the robustness of the circadian rhythm substantially weakened, also affecting the ultradian components. The ultradian periods were reduced, suggesting breakdown of temperature generation. Moreover, differences between daytime and nighttime ultradian patterns decreased during illness, confirming the weakening of the circadian component. The results of the experiments show that both core temperature distribution and temperature rhythm were disrupted during the infection. These disruptions worsened after each episode of hypothermia, suggesting an alteration of the temperature regulatory system.

13359 Büscher, P., Shamamba, S.K.B., Ngoyi, D.M., Pyana, P., Baelmans, R., Magnus, E. & Overmeir, C.V., 2005. Susceptibility of Grammomys surdaster thicket rats to Trypanosoma brucei gambiense infection. Tropical Medicine and International Health , 10 (9): 850–855.

Büscher: Unit of Parasite Diagnostics, Department of Parasitology, Institute of Tropical Medicine, Antwerp, Belgium.

Human African trypanosomiasis is caused by Trypanosoma brucei gambiense and T. b. rhodesiense . Historically, a treatment relapse rate of about 5 percent is observed in patients treated with melarsoprol, an arsenical derivative used for treatment of both gambiense and rhodesiense second stage sleeping sickness. More recently, relapse rates up to 30 percent are noted in gambiense sleeping sickness foci in Angola, Sudan and Uganda. Accordingly, WHO established a Network on Treatment Failure and Drug Resistance in Sleeping Sickness. One of its objectives is to improve isolation of T. b. gambiense from relapsing cases for research on drug resistance mechanisms. Trypanosoma b. gambiense isolation techniques suffer from low success rates and long periods needed to adapt the parasite to its new host. Usually, rodents are inoculated with patient's blood or cerebrospinal fluid and sub-passaged until the strain becomes sufficiently adapted to yield high parasitaemia within few days after inoculation. Until now, the best recipient for T. b. gambiense is Mastomys natalensis , with a success rate of about 50 percent. In this study, Grammomys surdaster (formerly Thamnomys surdaster) was investigated as a potential recipient for isolation of T. b. gambiense . Comparative experimental infections of Swiss mice, Wistar rats and G. surdaster thicket rats with T. b. gambiense clearly show that this trypanosome grows faster in G. surdaster . Inoculation of the same rodent species with patient's blood and cerebrospinal fluid in Kinshasa (R.D. Congo) confirms the observation that the thicket rats are more susceptible to T. b. gambiense infection than typical laboratory rodents.

13360 Chevrier, C., Canini, F., Darsaud, A., Cespuglio, R., Buguet, A. & Bourdon, L., 2005. Clinical assessment of the entry into neurological state in rat experimental African trypanosomiasis. Acta Tropica , 95 (1): 33–39.

Chevrier: Centre de recherches du service de santé des armées, Département des Facteurs Humains, 24 avenue des Maquis du Grésivaudan, BP 87, 38702 La Tronche, France.

Human African trypanosomiasis, caused by Trypanosoma brucei gambiense or T. b. rhodesiense , evolves in two stages: the haemolymphatic stage and the meningoencephalitic stage, the latter featuring numerous neurological disorders. In experimental models infected with diverse T. brucei sub-species, body weight (BW) loss, drop in food intake (FI), and hypo-activity after an asymptomatic period suggest the occurrence of a similar two-stage organization. In addition to daily measurement of BW and FI, body core temperature (Tco) and spontaneous activity (SA) were recorded by telemetry in T. b. brucei-infected rats. After a 10-to 12-day symptom-free period, a complex clinical syndrome suddenly occurred. If the animal survived the crisis, the syndrome recurred at approximately 5-day intervals until death. The syndrome consisted of a drop in FI and BW, a sharp decrease in Tco and a loss of SA, suggesting a rapid alteration of the central nervous system functioning. Such events confirm the existence of a two-stage disease development in experimental trypanosomiasis. The entry into the second stage is marked by the occurrence of the first crisis, with tracking of the BW being essential and often sufficient for its determination.

13361 Drennan, M.B., Stijlemans, B., Abbeele, J. van den, Quesniaux, V.J., Barkhuizen, M., Brombacher, F., Baetselier, P. de, Ryffel, B. & Magez, S., 2005. The induction of a type 1 immune response following a Trypanosoma brucei infection is MyD88 dependent. [Mice] Journal of Immunology , 175 (4): 2501–2509.

Drennan: Immunology of Infectious Disease Medical Research Council/University of Cape Town Unit, Institute of Infectious Disease and Molecular Medicine, Health Science Faculty, University of Cape Town, Cape Town, South Africa.

The initial host response toward the extracellular parasite Trypanosoma brucei is characterized by the early release of inflammatory mediators associated with a type 1 immune response. In this study, we show that this inflammatory response is dependent on activation of the innate immune system mediated by the adaptor molecule MyD88. In the present study, MyD88-deficient macrophages are nonresponsive toward both soluble VSG (variant-specific surface glycoprotein), as well as membrane-bound VSG purified from T. brucei . Infection of MyD88-deficient mice with either clonal or nonclonal stocks of T. brucei resulted in elevated levels of parasitemia. This was accompanied by reduced plasma IFN-γ and TNF levels during the initial stage of infection, followed by moderately lower VSG-specific IgG2a Ab titers during the chronic stages of infection. Analysis of several TLR-deficient mice revealed a partial requirement for TLR9 in the production of IFN-γ and VSG-specific IgG2a Ab levels during T. brucei infections. These results implicate the mammalian TLR family and MyD88 signaling in the innate immune recognition of T. brucei .

13362 Sallau, A.B., Nok, A.J., Ndams, I.S. & Balogun, E.O., 2004. Role of sialic acids in the midguts of Trypanosoma congolense infected Culex pipiens pipiens mosquitoes. African Journal of Biotechnology , 3 (8): 405–408.

Balogun: Department of Biochemistry, Ahmadu Bello University, Zaria, Nigeria.

Free and total sialic acid concentrations were determined in the midgut extracts of Culex pipiense pipiense mosquitoes infected with Trypanosoma congolense . The mean total sialic acid concentrations were found to be 1.5 to 2 fold higher than the mean free sialic acid concentrations in the midgut extracts of all the groups of the T. congolense infected C. p. pipiense . Infusion of 10 mg/ml galactose and 10 mg/ml lactose did not change the pattern of this difference but resulted to 1.3 to 1.4 fold decrease in the total sialic acid concentration. The relevance of these findings to the role of sialic acids in the midgut of T. congolense infected C. p. pipiense mosquitoes is discussed.

(c) CHEMOTHERAPEUTICS

13363 Ansede, J.H., Voyksner, R.D., Ismail, M.A., Boykin, D.W., Tidwell, R.R. & Hall, J.E., 2005. In vitro metabolism of an orally active O-methyl amidoxime prodrug for the treatment of CNS trypanosomiasis. Xenobiotica , 35 (3): 211–226.

Ansede: Division of Drug Delivery and Disposition, School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, N. Carolina, USA

13364 Anthony, J.P., Fyfe, L. & Smith, H., 2005. Plant active components -a resource for antiparasitic agents? Trends in Parasitology , 21 (10): 462–468.

Smith: Scottish Parasite Diagnostic Laboratory, Stobhill Hospital, Glasgow G21 3UW, UK.

Plant essential oils (and/or active components) can be used as alternatives or adjuncts to current antiparasitic therapies. Garlic oil has broad-spectrum activity against Trypanosoma , Plasmodium , Giardia and Leishmania , and Cochlospermum planchonii and Croton cajucara oils specifically inhibit Plasmodium falciparum and Leishmania amazonensis , respectively. Some plant oils have immunomodulatory effects that could modify host-parasite immunobiology, and the lipid solubility of plant oils might offer alternative, transcutaneous delivery routes. The emergence of parasites resistant to current chemotherapies highlights the importance of plant essential oils as novel antiparasitic agents.

13365 Arafa, R.K., Brun, R., Wenzler, T., Tanious, F.A., Wilson, W.D., Stephens, C.E. & Boykin, D.W., 2005. Synthesis, DNA affinity, and antiprotozoal activity of fused ring dicationic compounds and their prodrugs. Journal of Medicinal Chemistry , 48 (17): 5480–5488.

Boykin: Department of Chemistry, Center for Biotechnology and Drug Design, Georgia State University, Atlanta, GA 30303-3083, USA.

13366 Atawodi, S.E., 2005. Comparative in vitro trypanocidal activities of petroleum ether, chloroform, methanol and aqueous extracts of some Nigerian savannah plants. African Journal of Biotechnology , 4 (2): 177–182.

Atawodi: Biochemistry Department, Ahmadu Bello University, Zaria, Nigeria. [atawodise@yahoo.com]

Using Trypanosoma brucei as test organism, about two hundred extracts of varying polarities obtained from different parts of about forty tropical plants harvested from the savannah vegetational belt of Nigeria, were evaluated for their in vitro trypanocidal activities at concentrations of 2 and 4 mg/ml. The proportion of petroleum ether, chloroform, methanol and aqueous extracts that eliminated motility within 60 min at the highest concentration tested were 77, 67, 50 and 47 percent, respectively, while 10, 11, 19 and 14 percent of these extracts were completely non-active under the test condition. Among the plants studied, extracts of Adenium obesum (stem bark), Afrormosia laxiflora (leaves and stem bark), Cochlospermum planchoni (stem bark), Prosopis africana (stem and root barks), Striga spp. (leaves), Terminalia avicennioides (root and stem bark) and Swartzia madagascariensis (fruit pulp) exhibited the highest trypanocidal activity. These results suggest that tropical plants could be a very promising source of new generations of trypanocidal agents.

13367 Baliani, A., Bueno, G.J., Stewart, M.L., Yardley, V., Brun, R., Barrett, M.P. & Gilbert, I.H., 2005. Design and synthesis of a series of melamine-based nitroheterocycles with activity against trypanosomatid parasites. Journal of Medicinal Chemistry , 48 (17): 5570–5579.

Gilbert: Welsh School of Pharmacy, Redwood Building, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK.

The parasites that give rise to human African trypanosomiasis (HAT) are auxotrophs for various nutrients from the human host, including purines. They have specialist nucleoside transporters to import these metabolites. In addition to uptake of purine nucleobases and purine nucleosides, one of these transporters, the P2 transporter, can carry melamine derivatives; these derivatives are not substrates for the corresponding mammalian transporters. In this paper, we report the coupling of the melamine moiety to selected nitroheterocycles with the aim of selectively delivering these compounds to the parasites. Some compounds prepared have similar in vitro trypanocidal activities as melarsoprol, the principal drug used against late-stage HAT, with 50 percent growth inhibitory concentrations in the submicromolar range. Selected compounds were also evaluated in vivo in rodent models infected with Trypanosoma brucei brucei and T. brucei rhodesiense and showed pronounced activity and in two cases were curative without overt signs of toxicity. Compounds were also tested against other trypanosomatid pathogens, Leishmania donovani and Trypanosoma cruzi , and significant activity in vitro was noted for T. cruzi against which various nitroheterocycles are already registered for use.

13368 Chérigo, L., Polanco, V., Ortega-Barria, E., Heller, M.V., Capson, T.L. & Rios, L.C., 2005. Antitrypanosomal activity of a novel norlignan purified from Nectandra lineata . Natural Product Research , 19 (4): 373–377.

Rios: Laboratory of Natural Products, Faculty of Natural and Exact Sciences and Technology, Apdo. 0824, University of Panama, Panama City, Republic of Panama.

13369 Delespaux, V., Geysen, D., Majiwa, P.A.O. & Geerts, S., 2005. Identification of a genetic marker for isometamidium chloride resistance in Trypanosoma congolense . International Journal for Parasitology , 35 (2): 235–243.

Delespaux: Institute of Tropical Medicine, Nationalestraat 155, B-2000 Antwerp, Belgium.

Isometamidium chloride has remained a very important prophylactic and therapeutic drug against trypanosomosis in cattle since its introduction into the market in the 1950s with, unfortunately, a concomitant development of resistance in trypanosomosis endemic areas. Amplified Fragment Length Polymorphism (AFLP) was used to compare two isogenic clones of Trypanosoma congolense . The parent clone, sensitive to isometamidium, has a CD50 (the curative dose that gives complete cure in 50 percent of the animals) in the mouse of 0.018 mg/kg and its derivative exposed to increasing doses of isometamidium, has a CD50 that is 94-fold higher. Sixty-four combinations of eight Eco RI and eight Mse I primers were used in comparative AFLP analysis to detect subtle genetic differences between the two clones. Thirty-five polymorphic fragments of DNA that were observed only in the resistant clone were purified and then sequenced. The nucleotide sequences were used in searching the GeneDB T. congolense database to find surrounding sequences upstream of an open reading frame and downstream to a stop codon. The sequences of the open reading frames were subsequently compared to the sequences in the genomic databases. A predicted gene coding for an 854 amino acids protein was thus identified. The protein contains a putative ATP binding site, Walker B and LSGG motifs and eight predicted trans-membrane domains. The gene in the resistant strain of T. congolense has a triplet insertion coding for an extra lysine. Using polymerase chain reaction-restriction fragment length polymorphism, the insertion was sought in the genomes of 35 T. congolense strains isolated from different geographic origins and whose response to isometamidium chloride had been determined through single dose mouse tests. The presence of the insertion, specifying an extra codon, was found to always be present in the genomes of T. congolense clones that were resistant to isometamidium chloride.

13370 Hoet, S., Opperdoes, F., Brun, R. & Quetin-Leclercq, J., 2004. Natural products active against African trypanosomes: a step towards new drugs. Natural Product Reports , 21 (3): 353–364.

Hoet: Laboratoire de Pharmacognosie, Unité d'Analyse Chimique et Physico-Chimique des Médicaments, Université Catholique de Louvain, Av. E. Mounier 72, UCL 72.30-CHAM, B-1200, Brussels, Belgium. [sara.hoet@cham.ucl.ac.be]

13371 Ismail, M.A., Brun, R., Wenzler, T., Tanious, F.A., Wilson, W.D. & Boykin, D. W., 2004. Novel dicationic imidazo[1,2-α]pyridines and 5,6,7,8-tetrahydroimidazo[1,2-α]pyridines as antiprotozoal agents. [mice] Journal of Medicinal Chemistry , 47 (14): 3658–3664.

Ismail: Department of Chemistry and Center for Biotechnology and Drug Design, Georgia State University, Atlanta, GA 30303-3083, USA.

13372 Katete, D.P., McIntosh, R.J. & Lubega, G.W., 2004. Antibodies to recombinant tubulin can kill trypanosomes in culture. Molecular Biology of the Cell , 15 (Suppl.): 463a.

Katete: Veterinary Parasitology and Microbiology, Makarere University, Kampala, Uganda.

An antiserum against recombinant tubulin can kill trypanosomes in vitro ; the mechanism is still unclear and requires further study as part of the general effort needed towards developing a vaccine against sleeping sickness and/or nagana.

13373 Kubata, B.K., Nagamune, K., Murakami, N., Merkel, P., Kabututu, Z., Martin, S.K., Kalulu, T.M., Haq Mustakuk, Yoshida, M., Ohnishi-Kameyama, M., Kinoshita, T., Duszenko, M. & Urade, Y., 2005. Kola acuminata proanthocyanidins: a class of anti-trypanosomal compounds effective against Trypanosoma brucei . International Journal for Parasitology , 35 (1): 91–103.

Kubata: Department of Molecular Behavioral Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan.

Human African trypanosomiasis is undergoing an alarming rate of recrudescence in many parts of sub-Saharan Africa. Yet, there is no successful chemotherapy for the disease due to a limited number of useful drugs, side effects and drawbacks of the existing medication, as well as the development of drug resistance by the parasite. Here we describe a new lead anti-trypanosomal compound isolated from Kola acuminata (Makasu). We purified a proanthocyanidin by chromatographic procedures and confirmed its homogeneity and structure by Nuclear Magnetic Resonance and Matrix-Assisted Laser Desorption Ionization Time-of-Flight mass spectrometry, respectively. In vitro , this compound potently induced growth arrest and lysis of the bloodstream form trypanosomes in a dose-and time-dependent manner. In a mouse model, it exhibited a trypanostatic effect that extended the life of infected, treated animals up to 8 days postinfection against the 4 days for infected, untreated animals. The proanthocyanidin showed a low cytotoxicity against mammalian cells, whereas treated-bloodstream form showed massive enlargement of their flagellar pocket and lysosome-like structures caused by an intense formation of multivesicular bodies and vesicles within these organelles. The observed ultrastructural alterations caused rupture of plasma membranes and the release of cell contents, indicative of a necrotic process rather than a programmed cell death. Interestingly, the proanthocyanidin acted against the bloodstream form but not the procyclic form trypanosomes. This new anti-trypanosomal compound should be further studied to determine its efficacy and suitability as an anti-trypanosomal drug and may be used as a tool to define novel specific drug targets in bloodstream trypanosomes.

13374 Maikaje, D.B., 2000. Study on the sensitivity of a Trypanosoma brucei isolate from the Kaura Local Government Area to trypanocides. West African Journal of Biological Sciences , 11: 65–70.

Maikaje: Department of Biological Sciences, Nigerian Defence Academy, PMB 2109, Kaduna, Nigeria.

The sensitivity of Trypanosoma brucei brucei , the species most commonly isolated from cattle in Kaura LGA of Kaduna State, to Berenil and Samorin at dosages of 7mg/kg and 0.5mg/kg body weight was experimentally investigated in six Red Sokoto goats. The T. b. brucei isolate showed high sensitivities to these trypanocides which resulted in complete cure of the goats experimentally infected with it. This observation, which supports similar results obtained from Berenil treatment of natural bovine trypanosomiasis in this LGA, tends to suggest the non-existence of a drug-resistant strain of T. b. brucei in this area.

13375 Maikaje, D.B., 2001. Preliminary investigations on the therapeutic activities of diminazene and isometamidium on a Trypanosoma congolense isolate from the Kaura endemic focus of bovine trypanosomosis. Academy Journal of Science and Engineering , 1 (1): 16–24.

Maikaje: Department of Biological Sciences, Nigerian Defence Academy, PMB 2109, Kaduna, Nigeria.

The therapeutic responses of a Trypanosoma congolense isolate obtained from the bovine trypanosomosis endemic focus of Kaura Local Government Area, to diminazene aceturate and isometamidium chloride, were investigated. Three goats infected with this trypanosome isolate were completely cured within 24 hours of isometamidium treatment, and remained trypanosomosis-free until the study was completed 10 weeks later. However, there was a lapsed infection in one of two infected goats 17 days after diminazene aceturate treatment cleared the initial parasitaemia within 24 hours. In spite of the clearance of the T. congolense parasitaemia in the cured animals by these trypanocides, the declining trend in the values of the clinical parameters observed from the onset of the infection never reversed to normal values even during the ten weeks posttreatment monitoring. Isometamidium chloride at a dosage of 0.5 mg/kg body weight cleared the relapsed infections initially treated with diminazene. The continuous decline in clinical parameters in treated aparasitaemic goats in this study could be attributed to the cytotoxic effects of T. congolense- derived substances and/or the effects of confinement of these experimental animals which were used to grazing over long distances in their natural habitats. The initial treatment of trypanosomosis positive cases with the cheap diminazene followed by isometamidium treatment of relapsed cases and vector trapping are suggested for the effective control of bovine trypanosomosis in Kaura LGA.

13376 Ngamga, D., Yankep, E., Tane, P., Bezabih, M., Ngadjui, B.T., Fomum, Z.T. & Abegaz, B.M., 2005. Antiparasitic prenylated isoflavonoids from seeds of Millettia griffoniana . Bulletin of the Chemical Society of Ethiopia , 19 (1): 75–80.

Abegaz: Department of Chemistry, Faculty of Science, University of Botswana, POBox UB00704, Gaborone, Botswana.

Two new prenylated isoflavonoids, namely 7-methoxyebenosin and griffonianone E along with the known calopogonium isoflavone B and 7,2'-dimethoxy-4',5'methylenedioxy isoflavone were isolated from the seeds of Millettia griffoniana . Their structures were assigned on the basis of spectroscopic data. The new compounds exhibit moderate trypanocidal and antiplasmodial activities.

13377 Nyarko, E., Hara, T., Grab, D.J. & Fukuma, T., 2004. Trypanocidal effects of Au(III) in the presence of alamarBlueTM. An in vitro study. Molecular Biology of the Cell , 15 (Suppl.): 464a.

Trypanocidal toxicity tests are described involving possible synergy between Au(III) and the proprietary dye alamarBlue.

13378 Roch, P., Beschin, A. & Bernard, E., 2004. Antiprotozoan and antiviral activities of non-cytotoxic truncated and variant analogues of mussel defensin. Evidence-based Complementary and Alternative Medicine , 1 (2): 167–174.

Roch: Pathogènes et Immunité, UMR Ecosystèmes Lagunaires, Université de Montpellier 2, cc 093, Place E. Bataillon, 34095 Montpellier Cedex 5, France. [proch@univ-montp2.fr]

13379 Seebacher, W., Brun, R., Kaiser, M., Saf, R. & Weis, R., 2005. Synthesis and evaluation of the antitrypanosomal and antiplasmodial activities of new 4aminobicyclo[2.2.2] octane derivatives. European Journal of Medicinal Chemistry , 40 (9): 888–896.

Seebacher: Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl-Franzens-University, Universitätsplatz 1, A-8010 Graz, Austria.

13380 Shah, S.T.A., Merkel, P., Ragge, H., Duszenko, M., Rademann, J. & Voelter, W., 2005. Stereospecific synthesis of chiral 2,3-dihydro-1,4-benzodithiine and methyl-2,3-dihydro-1,4-benzodithiine derivatives and their toxic effects on Trypanosoma brucei . Chembiochem , 6 (8): 1438–1441.

Voelter: Physiologisch-chemisches Institut der Universität Tübingen, Hoppe-Seyler Strasse 4, 72076 Tübingen, Germany.

13381 Soeiro, M.N.C., De Souza, E.M., Stephens, C.E. & Boykin, D.W., 2005. Aromatic diamidines as antiparasitic agents. Expert Opinion on Investigational Drugs , 14 (8): 957–972.

Soeiro: Fiocruz MS, Lab Biologia Celular, Instituto Oswaldo Cruz DUBC, Avenida Brasil 4365, BR-21045900 Rio De Janeiro, Brazil.

Parasitic infections are widespread in developing countries and in developed countries are frequently associated with immunocompromised patients. Consequently, such infections are responsible for a significant amount of human mortality, morbidity and economic hardship. A growing consensus has identified the urgent need for the development of new antiparasitic compounds, mostly due to the large number of drugresistant parasites and the fact that currently available drugs are expensive, highly toxic, require long treatment regimens and frequently exhibit significantly reduced activity towards certain parasite strains and evolutive stages. In this context, the activity of aromatic diamidines has been explored against a widespread range of microorganisms, and the authors' present aim is to review the current status of chemotherapy with these compounds against human parasitic infections.

13382 Sternberg, J.M., Rodgers, J., Bradley, B., MacLean, L., Murray, M. & Kennedy, P.G.E., 2005. Meningoencephalitic African trypanosomiasis: Brain IL-10 and IL-6 are associated with protection from neuro-inflammatory pathology. Journal of Neuroimmunology , 167 (1–2): 81–89.

Sternberg: School of Biological Sciences, Zoology Building, University of Aberdeen, Aberdeen AB24 2TZ, UK.

The relationship of neuropathology to CNS inflammatory and counterinflammatory cytokine production in African trypanosome-infected mice was studied using an infection model with a defined disease progression. The initial phase of CNS infection by trypanosomes, where only mild neuropathology is evident, was characterised by high levels of IL-10 and IL-6. In the later phase of CNS infection and in a post-drug treatment model, moderate to severe neuropathology was associated with high levels of IFN-γ and TNF-α. The relationship of these cytokines to neuropathological grade suggests that IL-10 and IL-6 protect the CNS from inflammatory pathology when parasites first enter the brain and the data reconcile previously contradictory clinical measurements of CSF cytokines in meningoencephalitic patients with post-mortem histopathology observations.

13383 Steverding, D. & Tyler, K.M., 2005. Novel antitrypanosomal agents. Expert Opinion on Investigational Drugs , 14 (8): 939–955.

Steverding: School of Medicine, Health Policy and Practice, University of East Anglia, Norwich NR4 TJ7, Norfolk, UK.

Trypanosomes are the causative agents of Chagas' disease in Central and South America and sleeping sickness in sub-Saharan Africa. The current chemotherapy of the human trypanosomiases relies on only six drugs, five of which were developed > 30 years ago. In addition, these drugs display undesirable toxic side effects and the emergence of drug-resistant trypanosomes has been reported. Therefore, the development of new drugs in the treatment of Chagas' disease and sleeping sickness is urgently required. This article summarises the recent progress in identifying novel lead compounds for antitrypanosomal chemotherapy. Particular emphasis is placed on those agents showing promising, selective antitrypanosomal activity.

13384 Wurochekke, A.U. & Nok, A.J., 2004. In vitro antitrypanosomal activity of some medicinal plants used in the treatment of trypanosomosis in northern Nigeria. African Journal of Biotechnology , 3 (9): 481–483.

Wurochekke: Biochemistry Department, Federal University of Technology, Yola, Nigeria. [wchekke@yahoo.co.uk]

The in vitro trypanocidal activity of 13 medicinal plants (Cassia sieberiana, Ximenia americana, Ziziphus spina-christi, Z. abyssinica, Guiera senegalensis, Maytenus senegalensis, Albizia lebbeck, Cassia siamea, Tamarindus indica, Lawsonia inermis, Balanites aegyptiaca, Khaya senegalensis and Vernonia amygdalina) used by local herdsmen in northern Nigeria for the treatment of trypanosomosis was investigated. Forty-four extracts prepared from the 13 plants were screened for in vitro activity against Trypanosoma brucei brucei . Four of the extracts (extracts of G. senegalensis roots, T. indica leaves, and K. senegalensis bark) showed activity against the parasite at a minimum concentration of 8.3 mg/ml of blood.

8. TRYPANOSOME RESEARCH

(a) CULTIVATION OF TRYPANOSOMES

(b) TAXONOMY, CHARACTERIZATION OF ISOLATES

[See also 28: nos. 13321, 13331, 13341, 13353, 13354, 13369]

13385 Adl, S.M., Simpson, A.G.B., Farmer, M.A., Andersen, R.A., Anderson, O.R., Barta, J.R., Bowser, S.S., Brugerolle, G., Fensome, R.A., Fredericq, S., James, T.Y., Karpov, S., Kugrens, P., Krug, J., Lane, C.E., Lewis, L.A., Lodge, J., Lynn, D.H., Mann, D.G., McCourt, R.M., Mendoza, L., Moestrup, Ø., Mozley-Standridge, S.E., Nerad, T.A., Shearer, C.A., Smirnov, A.V., Spiegel, F.W., & Taylor, M.F.J.R., 2005. The new higher level classification of eukaryotes with emphasis on the taxonomy of protists. Journal of Eukaryotic Microbiology , 52 (5): 399–451

Adl: Department of Biology, Dalhousie University, Halifax, NSB3H 4JI Canada.

A new higher level classification of eukaryotes is presented. Regarding the genus Trypanosoma , this is placed within the following successively more inclusive groups: Trypanosomatida Kent, Metakinetoplastida Vickerman, Kinetoplastea Honigberg, Euglenozoa Cavalier-Smith, and Excavata Cavalier-Smith.

13386 Hamilton, P.B., Stevens, J.R., Gaunt, M.W., Gidley, J. & Gibson, W.C., 2004. Trypanosomes are monophyletic: evidence from genes for glyceraldehyde phosphate dehydrogenase and small subunit ribosomal RNA. International Journal for Parasitology , 34 (12): 1393–1404.

Gibson: School of Biological Sciences, University of Bristol, Bristol BS8 1UG, UK.

The genomes of Trypanosoma brucei , Trypanosoma cruzi and Leishmania major have been sequenced, but the phylogenetic relationships of these three protozoa remain uncertain. We have constructed trypanosomatid phylogenies based on genes for glycosomal glyceraldehyde phosphate dehydrogenase (gGAPDH) and small subunit ribosomal RNA (SSU rRNA). Trees based on gGAPDH nucleotide and amino acid sequences (51 taxa) robustly support monophyly of the genus Trypanosoma , which is revealed to be a relatively late-evolving lineage of the family Trypanosomatidae. Other trypanosomatids, including the genus Leishmania , branch paraphyletically at the base of the trypanosome clade. On the other hand, analysis of the SSU rRNA gene data produced equivocal results, as trees either robustly support or reject monophyly depending on the range of taxa included in the alignment. We conclude that the SSU rRNA gene is not a reliable marker for inferring deep level trypanosome phylogeny. The gGAPDH results support the hypothesis that trypanosomes evolved from an ancestral insect parasite, which adapted to a vertebrate/insect transmission cycle. This implies that the switch from terrestrial insect to aquatic leech vectors for fish and some amphibian trypanosomes was secondary. We conclude that the three sequenced pathogens, T. brucei , T. cruzi and L. major , are only distantly related and have distinct evolutionary histories.

13387 Simo, G. Herder, S., Njiokou, F., Asonganyi, T., Tilley, A. & Cuny, G., 2005. Trypanosoma brucei s.l.: characterisation of stocks from Central Africa by PCR analysis of mobile genetic elements. Experimental Parasitology , 110 (4): 353–362.

Simo: Laboratoire de Recherche sur les Trypanosomoses (LRT) OCEAC, P.O. Box 288, Yaoundé, Cameroon.

To better understand the epidemiology of sleeping sickness in the Central African sub-region, notably the heterogeneity of Human African Trypanosomiasis (HAT) foci, the mobile genetic element PCR (MGE-PCR) technique was used to genotype Trypanosoma brucei s.l. (T. brucei s.l.) isolates from this sub-region. Using a single primer REV B, which detects positional variation of the mobile genetic element RIME, via amplification of flanking regions, MGE-PCR revealed a micro genetic variability between Trypanosoma brucei gambiense (T. b. gambiense) isolates from Central Africa. The technique also revealed the presence of several T. b. gambiense genotypes and allowed the identification of minor and major ubiquitous genotypes in HAT foci. The presence of several T. b. gambiense genotypes in HAT foci may explain the persistence and the resurgence phenomena of the disease and also the epidemic and the endemic status of some Central African sleeping sickness foci. The MGE-PCR technique represents a simple, rapid, and specific method to differentiate Central African T. brucei s.l. isolates.

13388 Simonite, T., 2005. Protists push animals aside in rule revamp. Nature , 438 (7064): 8–9.

The article describes new perspectives on how the various types of eukaryotes should be classified. A group of protistologists have put forward the view that eukaryotes should be divided into six kingdoms, of which four are for protists, another group for animals and fungi (Opisthokonta), and a sixth group for plants (Archaeplastida). For the protists, one group (Amoeobazoa) comprises amoebae and slime moulds; another is Rhizaria; the third and fourth are termed Chromalveolata and Excavata. The last two are the most controversial of the groupings.

(c) LIFE CYCLE, MORPHOLOGY, BIOCHEMICAL AND MOLECULAR STUDIES

[See also 28: nos. 13362, 13369, 13378]

13389 Aitcheson, N., Talbot, S., Shapiro, J., Hughes, K., Adkin, C., Butt, T., Sheader, K. & Rudenko, G., 2005. VSG switching in Trypanosoma brucei : antigenic variation analysed using RNAi in the absence of immune selection. Molecular Microbiology , 57 (6): 1608–1622.

Rudenko: Peter Medawar Building, Pathogen Research, South Parks Road, University of Oxford, Oxford OX1 3SY, UK.

13390 Albert, M.A., Haanstra, J.R., Hannaert, V., Van Roy, J., Opperdoes, F.R., Bakker, B.M. & Michels, P.A.M., 2005. Experimental and in silico analyses of glycolytic flux control in bloodstream form Trypanosoma brucei . Journal of Biological Chemistry , 280 (31): 28306–28315.

Michels: Research Unit for Tropical Diseases, Christian de Duve Institute of Cellular Pathology, ICP-TROP 74.39, Université Catholique de Louvain, Ave. Hippocrate 74, B-1200 Brussels, Belgium. [michels@bchm.ucl.ac.be]

13391 Aphasizhev, R., 2005. RNA uridylyltransferases. [Review] Cellular and Molecular Life Sciences , 62 (19–20): 2194–2203.

Aphasizhev: Department of Microbiology and Molecular Genetics, B240-Medical Sciences I, University of California, Irvine, California 92697, USA.

13392 Archuleta, L., Dunham, A., Rains, J. & Fry, D., 2005. Differential tethering of log phase Trypanosoma brucei onto chemically distinct surfaces. ISIS International Symposium on Interdisciplinary Science , 755: 185–189.

Archuleta: Northwestern State University, Natchitoches, Louisiana, USA.

13393 Atrih, A., Richardson, J.M., Prescott, A.R. & Ferguson, M.A.J., 2005. Trypanosoma brucei glycoproteins contain novel giant poly-N acetyllactosamine carbohydrate chains. Journal of Biological Chemistry , 280 (2): 865–871.

Ferguson: University of Dundee School of Life Sciences, Wellcome Trust Biocentre, Dow St., Dundee DD1 5EH, Scotland, United Kingdom. [M.a.j.ferguson@dundee.ac.uk]

13394 Banerjee, S.K., Kessler, P.S., Saveria, T. & Parsons, M., 2005. Identification of trypanosomatid PEX19: functional characterization reveals impact on cell growth and glycosome size and number. Molecular and Biochemical Parasitology , 142 (1): 47–55.

Parsons: Seattle Biomedical Research Institute, 307 Westlake Avenue N., Seattle, WA 98109, USA.

13395 Barth, S., Hury, A., Liang, X.H. & Michaeli, S., 2005. Elucidating the role of H/ACA-like RNAs in trans-splicing and rRNA processing via RNA interference silencing of the Trypanosoma brucei CBF5 pseudouridine synthase. Journal of Biological Chemistry , 280 (41): 34558–34568.

Michaeli: Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel. [michaes@mail.biu.ac.il]

13396 Beitz, E., 2005. Aquaporins from pathogenic protozoan parasites: structure, function and potential for chemotherapy. Biology of the Cell , 97 (6): 373–383.

Beitz: Department of Pharmaceutical Chemistry, University of Tübingen, Morgenstelle 8, D-72076 Tübingen, Germany. [eric.beitz@uni.tuebingen. de]

13397 Benz, C., Nilsson, D., Andersson, B., Clayton, C., & Guilbride, D.L., 2005. Messenger RNA processing sites in Trypanosoma brucei . Molecular and Biochemical Parasitology , 143 (2): 125–134.

Andersson: Centre for Genomics and Bioinformatics, Karolinska Institutet, Berzelius väg 35, S-171 77 Stockholm, Sweden.

13398 Berriman, M., Ghedin, E., Hertz-Fowler, C., Blandin, G., Renauld, H., Bartholomeu, D.C., Lennard, N.J., Caler, E., Hamlin, N.E., Haas, B., Böhme, U., Hannick, L., Aslett, M.A., Shallom, J., Marcello, L., Hou, L.H., Wickstead, B., Alsmark, U.C.M., Arrowsmith, C., Atkin, R.J., Barron, A.J., Bringaud, F., Brooks, K., Carrington, M., Cherevach, I., Chillingworth, T.J., Churcher, C., Clark, L.N., Corton, C.H., Cronin, A., Davies, R,M., Doggett, J., Djikeng, A., Feldblyum, T., Field, M.C., Fraser, A., Goodhead, I., Hance, Z., Harper, D., Harris, B.R., Hauser, H., Hostetler, J., Ivens, A., Jagels, K., Johnson, D., Johnson, J., Jones, K., Kerhornou, A.X., Koo, H., Larke, N., Landfear, S., Larkin, C., Leech, V., Line, A., Lord, A., MacLeod, A., Mooney, P.J., Moule, S., Martin, D.M.A., Morgan, G.W., Mungall, K., Norbertczak, H., Ormond, D., Pai, G., Peacock, C.S., Peterson, J., Quail, M.A., Rabbinowitsch, E., Rajandream, M.-A., Reitter, C., Salzberg, S.L., Sanders, M., Schobel, S., Sharp, S., Simmonds, M., Simpson, A.J., Tallon, L., Turner, M.R., Tait, A., Tivey, A.R., Van Aken, S., Walker, D., Wanless, D., Wang, S., White, B., White, O., Whitehead, S., Woodward, J., Wortman, J., Adams, M.D., Embley, T.M., Gull, K., Ullu, E., Barry, J.D., Fairlamb, A.H., Opperdoes, F., Barrell, B.G., Donelson, J.E., Hall, N., Fraser, C.M., Melville, S.E. & El-Sayed, N.M., 2005. The genome of the African trypanosome Trypanosoma brucei . Science , 309 (5733): 416–422, 423–431, 435.

Berriman: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK. [mb4@sanger.ac.uk]

African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of Trypanosoma brucei . The 26-megabase genome contains 9 068 predicted genes, including ~900 pseudogenes and ~1 700 T. brucei specific genes. Large subtelomeric arrays contain an archive of 806 variant surface glycoprotein (VSG) genes used by the parasite to evade the mammalian immune system. Most VSG genes are pseudogenes, which may be used to generate expressed mosaic genes by ectopic recombination. Comparisons of the cytoskeleton and endocytic trafficking systems with those of humans and other eukaryotic organisms reveal major differences. A comparison of metabolic pathways encoded by the genomes of T. brucei , T. cruzi , and Leishmania major reveals the least overall metabolic capability in T. brucei and the greatest in L. major . Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified.

13399 Byres, E., Martin, D.M.A. & Hunter, W.N., 2005. A preliminary crystallographic analysis of the putative mevalonate diphosphate decarboxylase from Trypanosoma brucei . Acta Crystallographica A Section F - Structural Biology and Crystallization Communications , 61 (6): 581–584.

Hunter: Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.

13400 Chaudhuri, M., Ott, R.D., Saha, L., Williams, S. & Hill, G.C., 2005. The trypanosome alternative oxidase exists as a monomer in Trypanosoma brucei mitochondria. Parasitology Research , 96 (3): 178–183.

Department of Microbiology, School of Medicine, Meharry Medical College, Nashville, TN 37208, USA. [mchaudhuri@mmc.edu]

13401 Chevalier, N., Bertrand, L., Rider, M.H., Opperdoes, F.R., Rigden, D.J. & Michels, P.A.M., 2005.6-Phosphofructo-2-kinase and fructose-2,6bisphosphatase in Trypanosomatidae: Molecular characterization, database searches, modelling studies and evolutionary analysis. FEBS Journal , 272 (14): 3542–3560.

Michels: Université catholique de Louvain, ICP-TROP 74-39, Avenue Hippocrate 74, B-1200, Brussels, Belgium. [michels@bchm.ucl.ac.be]

13402 Chung, W.C. & Kermode, J.C., 2005. Suramin disrupts receptor-G protein coupling by blocking association of G protein α and βγ subunits. Journal of Pharmacology and Experimental Therapeutics , 313 (1): 191–198.

Kermode: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 392164505, USA. [jkermode@pharmacology.umsmed.edu]

13403 Claes, F., Büscher, P., Touratier, L. & Goddeeris, B.M., 2005. Trypanosoma equiperdum : master of disguise or historical mistake? Trends in Parasitology , 21 (7): 316–321.

Claes: Faculty of Applied Bioscience and Engineering, Department of Animal Sciences, Katholieke Universiteit Leuven, Kasteelpark Arenberg 30, 3001 Leuven, Belgium.

After 100 years of research, only a small number of laboratory strains of Trypanosoma equiperdum exists, and the history of most of the strains is unknown. No definitive diagnosis of dourine can be made at the serological or molecular level. Only clinical signs are pathognomonic and international screening relies on an outdated crossreactive serological test (the complement-fixation test) from 1915, resulting in serious consequences at the practical level. Despite many characterization attempts, no clear picture has emerged of the position of T. equiperdum within the Trypanozoon group. In this article, we highlight the controversies that exist regarding T. equiperdum , and the overlap that occurs with Trypanosoma evansi and Trypanosoma brucei brucei . By revisiting the published data, from the early decades of discovery to the recent serological-and molecular-characterization studies, a new hypothesis arises in which T. equiperdum no longer exists as a separate species and in which current strains can be divided into T. evansi (the historical mistake) and Trypanosoma brucei equiperdum (the master of disguise). Hence, dourine is a disease caused by specific host immune responses to a T. b. equiperdum or T. evansi infection.

13404 Coustou, V., Besteiro, S., Rivière, L., Biran, M., Biteau, N., Franconi, J.M., Boshart, M., Baltz, T. & Bringaud, F., 2005. A mitochondrial NADHdependent fumarate reductase involved in the production of succinate excreted by procyclic Trypanosoma brucei . Journal of Biological Chemistry , 280 (17): 16559–16570.

Bringaud: Laboratoire de Génomique Fonctionnelle des Trypanosomatides, UMR-5162 CNRS, Université Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux cedex, France. [bringaud@u-bordeaux2.fr]

13405 Cross, G.A.M., 2005. Trypanosomes at the gates. [Editorial] Science , 309 (5733): 355.

Cross: Laboratory of Molecular Parasitology, Rockefeller University, New York, NY 10021, USA.

The question is posed: Why do the three trypanosomatid species Trypanosoma brucei , T. cruzi and Leishmania major , generate so much interest from scientists? The answer is largely, but only partly, that these are responsible for severe diseases in many parts of the warmer parts of the world. Additionally, these organisms are especially amenable to laboratory culture and study, and have unique features to do with their genetics and metabolic pathways, RNA editing and anchoring of proteins to membranes. The traditional pharmaceutical industry will not become involved in the vital task of transforming laboratory findings on suitable drug targets, into clinical successes. The idea is floated that perhaps the situation needs research institutes dedicated to “diseases of the poor”. Funding by donors such as the governments of the wealthier nations, and others, is needed to respond to these dangerous pathogens.

13406 Crossman, A. Jr., Smith, T.K., Ferguson, M.A.J. & Brimacombe, J.S., 2005. Synthesis of a cell-permeable analogue of a glycosylphosphatidylinositol (GPI) intermediate that is toxic to the living bloodstream form of Trypanosoma brucei . Tetrahedron Letters , 46 (43): 7419–7421.

Ferguson: School of Life Sciences, Division of Biological Chemistry and Molecular Microbiology, University of Dundee, The Wellcome Trust Biocentre, Dundee DD1 5EH, Scotland, UK. [m.a.j.ferguson@dundee. ac.uk]

13407 Das, A., Zhang, Q., Palenchar, J.B., Chatterjee, B., Cross, G.A.M. & Bellofatto, V., 2005. Trypanosomal TBP functions with the multisubunit transcription factor tSNAP to direct spliced-leader RNA gene expression. Molecular and Cellular Biology , 25 (16): 7314–7322.

Bellofatto: Department of Microbiology and Molecular Genetics, UMDNJ-NJ Medical School, International Center for Public Health, 225 Warren St., Newark, NJ 07103 USA. [bellofat@umdnj.edu]

13408 Dreesen, O., Li, B. & Cross, G.A.M., 2005. Telomere structure and shortening in telomerase-deficient Trypanosoma brucei . Nucleic Acids Research , 33 (14): 4536–4543.

Cross: Laboratory of Molecular Parasitology, The Rockefeller University 1230 York Avenue, NY 10021-6399, USA. [george.cross@rockefeller.edu]

13409 Dubois, M.E., Demick, K.P. & Mansfield, J.M., 2005. Trypanosomes expressing a mosaic variant surface glycoprotein coat escape early detection by the immune system. Infection and Immunity , 73 (5): 2690–2697.

Mansfield: Department of Bacteriology, University of Wisconsin-Madison, 1925 Willow Drive, Madison, WI 53706, USA. [jmm@bact.wisc.edu]

13410 El-Sayed, N.M., Myler, P.J., Bartholomeu, D.C., Nilsson, D., Aggarwal, G., Anh Nhi Tran, Ghedin, E., Worthey, E.A., Delcher, A.L., Blandin, G., Westenberger, S.J., Caler, E., Cerqueira, G.C., Branche, C., Haas, B.,Anupama, A., Arner, E., Åslund, L., Attipoe, P., Bontempi, E., Bringaud, F., Burton, P., Cadag, E., Campbell, D.A., Carrington, M., Crabtree, J., Darban, H., da Silveira, J.C., de Jong, P., Edwards, K., Englund, P.T., Fazekina, G., Feldblyum, T., Ferella, M., Frasch, A.C., Gull, K., Horn, D., Hou, L.H., Kindlund, E., Klingbeil, M., Kluge, S., Koo, H. Lacerda, D., Levin, M.J., Lorenzi, H., Louie, T., Machado, C.R., McCulloch, R., McKenna, A., Mizuno, Y., Mottram, J.C., Nelson, S., Ochaya, S., Ososegawa, K., Pai, G., Parsons, M., Pentony, M., Pettersson, U., Pop, M., Ramirez, J.L., Rinta, J., Robertson, L., Salzberg, S.L., Sanchez, D.O., Seyler, A., Sharma, R., Shetty, J., Simpson, A.J., Sisk, E., Tammi, M.T., Tarleton, R., Teixeira, S., Van Aken, S., Vogt, C., Ward, P.N., Wickstead, B., Wortman, J., White, O., Fraser, C.M., Stuart, K.D. & Andersson, B., 2005. The genome sequence of Trypanosoma cruzi , etiologic agent of Chagas disease. Science , 309 (5733): 409–415, 423–428, 435.

El-Sayed: Department of Parasite Genomics, The Institute for Genomic Research, Rockville, MD 20850, USA. [nelsayed@tigr.org]

Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that the diploid genome contains a predicted 22 570 proteins encoded by genes, of which 12 570 represent allelic pairs. Over 50 percent of the genome consists of repeated sequences, such as retrotransposons and genes for large families of surface molecules, which include trans-sialidases, mucins, gp63s, and a large novel family (>1 300 copies) of mucin-associated surface protein (MASP) genes. Analyses of the T. cruzi , T. brucei , and Leishmania major (Tritryp) genomes imply differences from other eukaryotes in DNA repair and initiation of replication and reflect their unusual mitochondrial DNA. Although the Tritryp lack several classes of signalling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention

13411 El-Sayed, N.M., Myler, P.J., Blandin, G., Berriman, M., Crabtree, J., Aggarwal, G., Caler, E., Renauld, H., Worthey, E.A., Hertz-Fowler, C., Ghedin, E., Peacock, C., Bartholomeu, D.C., Haas, B.J., Anh Nhi Tran, Wortman, J.R., Alsmark, U.C.M., Angiuoli, S., Anupama, A., Badger, J., Bringaud, F., Cadag, E., Carlton, J.M., Cerqueira, G.C., Creasy, T., Delcher, A.L., Djikeng, A., Ebley, T.M., Hauser, C., Ivens, A.C., Kummerfeld, S.K., Pereira-Leal, J.B., Nilsson, D., Peterson, J., Salzberg, S.L., Shallom, J., Silva, J.C., Sundaram, J., Westenberger, S., White, O., Melville, S.E., Donelson, J.E., Andersson, B., Stuart, K.D. & Hall, N., 2005. Comparative genomics of trypanosomatid parasitic protozoa. Science , 309 (5733): 404–409, 423–435.

El-Sayed: The Institute for Genomic Research, 9712 Medical Center Drive, Rockville, MD 20850, USA. [nelsayed@tigr.org]

A comparison of gene content and genome architecture of Trypanosoma brucei , T. cruzi , and Leishmania major , three related pathogens with different life cycles and disease pathology, revealed a conserved core proteome of about 6 200 genes in large syntenic polycistronic gene clusters. Many species-specific genes, especially large surface antigen families, occur at nonsyntenic chromosome-internal and subtelomeric regions. Retroelements, structural RNAs, and gene family expansion are often associated with syntenic discontinuities that - along with gene divergence, acquisition and loss, and rearrangement within the syntenic regions - have shaped the genomes of each parasite. Contrary to recent reports, the analyses reveal no evidence that these species are descended from an ancestor that contained a photosynthetic endosymbiont.

13412 Engstler, M. & Boshart, M., 2004. Cold shock and regulation of surface protein trafficking convey sensitization to inducers of stage differentiation in Trypanosoma brucei . Genes & Development , 18 (22): 2798–2811.

Engstler: Ludwig-Maximilians-Universität, Department Biologie I, Genetik, 80638 München, Germany. [engstler@lrz.uni-muenchen.de]

13413 Engstler, M., Weise, F., Bopp, K., Grünfelder, C.G., Günzel, M., Heddergott, N. & Overath, P., 2005. The membrane-bound histidine acid phosphatase TbMBAP1 is essential for endocytosis and membrane recycling in Trypanosoma brucei . Journal of Cell Science , 118 (10): 2105–2118.

Engstler: Ludwig-Maximilians-Universität, Department Biologie I, Genetik, Maria-Ward-Strasse 1a, München, 80638, Germany. [engstler@lrz.unimuenchen.de]

13414 Field, M.C., 2005. Signalling the genome: the Ras-like small GTPase family of trypanosomatids. Trends in Parasitology , 21 (10): 447–450.

Field: The Molteno Building, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK.

13415 Foldynová-Trantírková, S., Paris, Z., Sturm, N.R., Campbell, D.A. & Lukeš, J., 2005. The Trypanosoma brucei La protein is a candidate poly(U) shield that impacts spliced leader RNA maturation and tRNA intron removal. International Journal for Parasitology , 35 (4): 359–366.

Lukeš :Institute of Parasitology, Czech Academy of Sciences, Faculty of Biology, University of South Bohemia, 37005 České Budejovice, Czech Republic.

13416 Geiser, F., Luscher, A., de Koning, H.P., Seebeck, T. & Mäser, P., 2005. Molecular pharmacology of adenosine transport in Trypanosoma brucei : P1/P2 revisited. Molecular Pharmacology , 68 (3): 589–595.

Mäser: Institute of Cell Biology, Baltzerstrasse 4, CH-3012 Bern, Switzerland. [pascal.maeser@izb.unibe.ch]

13417 Gibson, W.C., 2005. The SRA gene: the key to understanding the nature of Trypanosoma brucei rhodesiense . Parasitology , 131 (2): 143–150.

Gibson: School of Biological Sciences, University of Bristol, Woodlands Road, Bristol BS8 1UG, UK. [w.gibson@bristol.ac.uk]

13418 Ginger, M.L., Ngazoa, E.S., Pereira, C.A., Pullen, T.J., Kabiri, M., Becker, K., Gull, K. & Steverding, D., 2005. Intracellular positioning of isoforms explains an unusually large adenylate kinase gene family in the parasite Trypanosoma brucei . Journal of Biological Chemistry , 280 (12): 11781–11789.

Gull: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK [keith.gull@pathology.oxford.ac.uk]

13419 Hendriks, E.F. & Matthews, K.R., 2005. Disruption of the developmental programme of Trypanosoma brucei by genetic ablation of TbZFP1, a differentiation-enriched CCCH protein. Molecular Microbiology , 57 (3): 706–716.

Matthews: Institute of Immunology and Infection Research, School of Biological Sciences, Ashworth Laboratories, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK. [keith.matthews@ed.ac.uk]

13420 Horn, D. & Barry, J.D., 2005. The central roles of telomeres and subtelomeres in antigenic variation in African trypanosomes. Chromosome Research , 13 (5): 525–533.

Barry: The Anderson College, University of Glasgow, 56 Dumbarton Rd, Glasgow, G11 6NU, UK. [j.d.barry@bio.gla.ac.uk]

13421 Horváth, A., Horáková, E., Dunaćíková, P., Verner, Z., Pravdová, E., Slapetová, I., Cuninková, L. & Lukeš, J., 2005. Downregulation of the nuclear-encoded subunits of the complexes III and IV disrupts their respective complexes but not complex I in procyclic Trypanosoma brucei . Molecular Microbiology , 58 (1): 116–130.

Lukeš: Institute of Parasitology, Czech Academy of Sciences and Faculty of Biology, University of South Bohemia, Branišovská 31, 37005 České Budĕjovice, Czech Republic. [jula@paru.cas.cz]

13422 Hutchings, N.R. & Ludu, A., 2005. Flagellar bend dynamics in African trypanosomes. ISIS International Symposium on Interdisciplinary Science , 755: 137–144.

Hutchings: Interdisciplinary Experimentation and Scholarship (IDEAS) Program, Department of Chemistry and Physics, Northwestern State University of Louisiana. Natchitoches, Louisiana 71497 USA.

13423 Ivens, A.C., Peacock, C.S., Worthey, E.A., Murphy, L., Aggarwal, G., Berriman, M., Sisk, E., Rajandream, M.A., Adlem, E., Aert, R., Anupama, A., Apostolou, Z., Attipoe, P., Bason, N., Bauser, C., Beck, A., Beverley, S.M., Bianchettin, G., Borzym, K., Bothe, G., Bruschi, C.V., Collins, M., Cadag, E., Ciarloni, L., Clayton, C., Coulson, R.M.R., Cronin, A., Cruz, A.K., Davies, R.M., De Gaudenzi, J., Dobson, D.E., Dueterhoeft, A., Fazelina, G., Fosker, N., Frasch, A.C., Fraser, A., Fuchs, M., Gabel, C., Goble, A., Goffeau, A., Harris, D., Hertz-Fowler, C., Hilbert, H., Horn, D., Huang, Y.T., Klages, S., Knights, A., Kube, M., Larke, N., Litvin, L., Lord, A., Louie, T., Marra, M., Masuy, D., Matthews, K., Michaeli, S., Mottram J.C., Müller-Auer, S., Munden, H., Nelson, S., Norbertczak, H., Oliver, K., O'Neil, S., Pentony, M., Pohl, T.M., Price, C., Purnelle, B., Quail, M.A., Rabbinowitsch, E., Reinhardt, R., Reiger, M., Rinta, J., Robben, J., Robertson, L., Ruiz, J.C., Rutter, S., Saunders, D., Schäfer, M., Schein, J., Schwartz, D.C., Seeger, K., Seyler, A., Sharp, S., Shin, H., Sivam, D., Squares, R., Squares, S., Tosato, V., Vogt, C., Volckaert, G., Wambutt, R., Warren, T., Wedler, H., Woodward, J., Zhou, S.G., Zimmerman, W., Smith, D.F., Blackwell, J.M., Stuart, K.D., Barrell, B. & Myler, P.J., 2005. The genome of the kinetoplastid parasite, Leishmania major . Science , 309 (5733): 436–442, 423–428, 432–435.

Ivens: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK. [alicat@sanger.ac.uk]

Leishmania species cause a spectrum of human diseases in tropical and subtropical regions of the world. We have sequenced the 36 chromosomes of the 32.8-megabase haploid genome of Leishmania major (Friedlin strain) and predict 911 RNA genes, 39 pseudogenes, and 8 272 protein-coding genes, of which 36 percent can be ascribed a putative function. These include genes involved in host-pathogen interactions, such as proteolytic enzymes, and extensive machinery for synthesis of complex surface glycoconjugates. The organization of protein-coding genes into long, strand-specific, polycistronic clusters and lack of general transcription factors in the L. major , Trypanosoma brucei , and T. cruzi (Tritryp) genomes suggest that the mechanisms regulating RNA polymerase II-directed transcription are distinct from those operating in other eukaryotes, although the trypanosomatids appear capable of chromatin remodeling. Abundant RNA-binding proteins are encoded in the Tritryp genomes, consistent with active posttranscriptional regulation of gene expression.

13424 Jensen, B.C., Brekken, D.L., Randall, A.C., Kifer, C.T. & Parsons, M., 2005. Species specificity in ribosome biogenesis: a nonconserved phosphoprotein is required for formation of the large ribosomal subunit in Trypanosoma brucei . Eukaryotic Cell , 4 (1): 30–35.

Parsons: Seattle Biomedical Research Institute, University of Washington, 307 Westlake Ave. N., Seattle, WA 98109-5219, USA.

13425 Jones, D.C., Mehlert, A., Guther, M.L.S. & Ferguson, M.A.J., 2005. Deletion of the glucosidase II gene in Trypanosoma brucei reveals novel Nglycosylation mechanisms in the biosynthesis of variant surface glycoprotein. Journal of Biological Chemistry , 280 (43): 35929–35942.

Ferguson: University of Dundee School of Life Sciences, Wellcome Trust Biocentre, Dow St., Dundee DD1 5EH, Scotland, United Kingdom. [M.a.j.ferguson@dundee.ac.uk]

13426 Kilunga, K.B., Inoue, T., Okano, Y., Kabututu, Z., Martin, S.K., Lazarus, M., Duszenko, M., Sumii, Y., Kusakari, Y., Matsumura, H., Kai, Y., Sugiyama, S., Inaka, K., Inui, T. & Urade, Y., 2005. Structural and mutational analysis of Trypanosoma brucei prostaglandin H2 reductase provides insight into the catalytic mechanism of aldo-ketoreductases. Journal of Biological Chemistry , 280 (28): 26371–26382.

Kilunga: United States Army Medical Research Unit-Kenya, Unit 64109, APO AE 09831-64109. [bkubata@nairobi.mimcom.net]

13427 Korbel, D.S., Finney, O.C. & Riley, E.M., 2004. Natural killer cells and innate immunity to protozoan pathogens. International Journal for Parasitology , 34 (13–14): 1517–1528.

Riley: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.

13428 Krauth-Siegel, R.L., Bauer, H. & Schirmer, H., 2005. Dithiol proteins as guardians of the intracellular redox milieu in parasites: Old and new drug targets in trypanosomes and malaria-causing plasmodia. Angewandte Chemie - International Edition , 44 (5): 690–715.

Kraut-Siegel: Biochemie-Zentrum der Universität Heidelberg, Im Neuenheimer Feld 504, 69120 Heidelberg, Germany. [kraut-siegel@urz. uni-heidelberg.de]

13429 Kumar, P. & Wang, C.C., 2005. Depletion of anaphase-promoting complex or cyclosome (APC/C) subunit homolog APC1 or CDC27 of Trypanosoma brucei arrests the procyclic form in metaphase but the bloodstream form in anaphase. Journal of Biological Chemistry , 280 (36): 31783–31791.

Wang: Dept. of Pharmaceutical Chemistry, UCSF, San Francisco, CA 94143-2280, USA. [ccwang@cgl.ucsf.edu]

13430 Lamour, N., Rivière, L., Coustou, V., Coombs, G.H., Barrett, M.P. & Bringaud, F., 2005. Proline metabolism in procyclic Trypanosoma brucei is down-regulated in the presence of glucose. Journal of Biological Chemistry , 280 (12): 11902–11910.

Barrett: Institute of Biomedical and Life Sciences, Division of Infection & Immunity, University of Glasgow, Glasgow G12 8QQ, UK. [m.barrett@ bio.gla.ac.uk]

13431 Li, B., Espinal, A., & Cross, G.A.M., 2005. Trypanosome telomeres are protected by a homologue of mammalian TRF2. Molecular and Cellular Biology , 25 (12): 5011–5021.

Cross: Laboratory of Molecular Parasitology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. [gamc@mail. rockefeller.edu]

13432 Liu, B.Y., Liu, Y.N., Motyka, S.A., Agbo, E.E.C. & Englund, P.T., 2005. Fellowship of the rings: the replication of kinetoplast DNA. Trends in Parasitology , 21 (8): 363–369.

Englund: Department of Biological Chemistry, Johns Hopkins Medical School, 725 North Wolfe Street, Baltimore, MD 21205, USA. [penglund@jhmi.edu]

13433 Lücke, S., Jürchott, K., Hung, L.H. & Bindereif, A., 2005. mRNA splicing in Trypanosoma brucei : Branch-point mapping reveals differences from the canonical U2 snRNA-mediated recognition. Molecular and Biochemical Parasitology , 142 (2): 248–251.

Bindereif: Insitut für Biochemie, Justus-Liebig-Universität Giessen, Heinrich-Buff-Ring 58, D-14059 Berlin, Germany.

13434 MacLeod, A., Tweedie, A., McLellan, S., Taylor, S., Cooper, A., Sweeney, L., Turner, C.M.R. & Tait, A., 2005. Allelic segregation and independent assortment in T. brucei crosses: proof that the genetic system is Mendelian and involves meiosis. Molecular and Biochemical Parasitology , 143 (1): 12–19.

MacLeod: Wellcome Centre for Molecular Parasitology, Anderson College, University of Glasgow, 56 Dumbarton Road, Glasgow G11 6NU, UK.

13435 MacLeod, A., Tweedie, A., McLellan, S., Taylor, S., Cooper, A., Sweeney, L., Turner, C.M.R. & Tait, A., 2005. Corrigendum to “Allelic segregation and independent assortment in T. brucei crosses: Proof that the genetic system is Mendelian and involves meiosis” [Molecular and Biochemical Parasitology , 143 (2005) 12–19], Molecular and Biochemical Parasitology, In Press, Corrected Proof, Available online 6 September 2005

13436 Mayer, M.G. & Floeter-Winter, L.M., 2005. Pre-mRNA trans-splicing: from kinetoplastids to mammals, an easy language for life diversity. Memorias do Instituto Oswaldo Cruz , 100 (5): 501–513.

Floeter-Winter: Departmento de Fisiologia, Instituto de Biociências, Rua do Matão, travessa 14, 101, 05508-900 São Paulo, SP. Brazil.

13437 McCulloch, R., Vassella, E., Burton, P., Boshart, M. & Barry, J.D., 2004. Transformation of monomorphic and pleomorphic Trypanosoma brucei . In: Genetic Recombination: Reviews and Protocols , in Methods in Molecular Biology series, Vol 262, pp. 53–86. Publ. Humana Press Inc., Ottowa, Jan 2004. ISBN 1-58829-236-3.

13438 Morrison, L.J., Majiwa, P., Read, A.F. & Barry, J.D., 2005. Probabilistic order in antigenic variation of Trypanosoma brucei . International Journal for Parasitology , 35 (9): 961–972.

Barry: Wellcome Centre for Molecular Parasitology, University of Glasgow, 56 Dumbarton Rd, Glasgow, G11 6NU, UK.

13439 Motta, M.C.M., Picchi, G.F.A., Palmie-Peixoto, I.V., Rocha, M.R.D.E. Carvalho, T.M.U., Morgado-Diaz, J.D.E., Souza, W., Goldenberg, S. & Fragoso, S.P., 2004. The microtubule analog protein, FtsZ, in the endosymbiont of trypanosomatid Protozoa. Journal of Eukaryotic Microbiology , 51 (4): 394–401.

Motta: Laboratório de Ultrastrutura Celular Hertha Meyer, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, BlocoG, Ilha do Fundão, 21941-900 Rio de Janeiro, RJ, Brazil.

13440 Mung'ong'o, S.G., Markham, A., Hooper, M., Fairlamb, A.H. & Berger, B.J., 2003. Activity of novel tryptophan analogs against mammalian and trypanosomal monoamine oxidases. East and Central African Journal of Pharmaceutical Sciences , 6 (2): 43–49.

Mung'ong'o: School of Pharmacy, Muhimbili University College of Health Sciences, P.O. Box 65013, Dar es salaam, Tanzania.

13441 Munro, S., 2005. The Arf-like GTPase Arl1 and its role in membrane traffic. Biochemical Society Transactions , 33 (4): 601–605.

Munro: MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.

13442 Nakamura, K., Sakamoto, K., Kido, Y., Fujimoto, Y., Suzuki, T., Suzuki, M., Yabu, Y., Ohta, N., Tsuda, A., Onuma, M. & Kita, K., 2005. Mutational analysis of the Trypanosoma vivax alternative oxidase: The E(X)6Y Motif is conserved in both mitochondrial alternative oxidase and plastid terminal oxidase and is indispensable for enzyme activity. Biochemical and Biophysical Research Communications , 334 (2): 593–600.

Kita: Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.

13443 Nasizadeh, S., Myhre, L., Thiman, L., Alm, K., Oredsson, S. & Persson, L., 2005. Importance of polyamines in cell cycle kinetics as studied in a transgenic system. Experimental Cell Research , 308 (2): 254–264.

Persson: Department of Physiological Sciences, Lund University, BMC F13, S-221 84 Lund, Sweden.

13444 Palfi, Z., Schimanski, B., Günzl, A., Lücke, S. & Bindereif, A., 2005. U1 small nuclear RNP from Trypanosoma brucei : a minimal U1 snRNA with unusual protein components. Nucleic Acids Research , 33 (8): 2493–2503.

Bindereif: Institut für Biochemie, Justus-Liebig-Universität Giessen Heinrich-Buff-Ring 58, D-35392 Giessen, Germany. [albrecht.bindereif@ chemie.bio.uni-giessen.de]

13445 Penschow, J.L., Sleve, D.A., Ryan, C.M. & Read, L.K., 2004. TbDSS-1, an essential Trypanosoma brucei exoribonuclease homolog that has pleiotropic effects on mitochondrial RNA metabolism. Eukaryotic Cell , 3 (5): 1206–1216.

Read: Department of Microbiology and Immunology, Witebsky Center for Microbial Pathogenesis and Immunology, 138 Farber Hall, SUNY Buffalo School of Medicine, Buffalo, NY 14214, USA. [lread@acsu.buffalo.edu]

13446 Pérez-Morga, D., Vanhollebeke, B., Paturiaux-Hanocq, F., Nolan, D.P., Lins, L., Homblé, F., Vanhamme, L., Tebabi, P., Pays, A., Poelvoorde, P., Jacquet, A., Brasseur, R. & Pays, E., 2005. Apolipoprotein L-I promotes trypanosome lysis by forming pores in lysosomal membranes. Science , 309 (5733): 469–472.

Pays: Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles, 12, rue des Profs Jeener et Brachet, B6041 Gosselies, Belgium. [epays@ulb.ac.be]

13447 Price, H.P., Goulding, D. & Smith, D.F., 2005. ARL1 has an essential role in Trypanosoma brucei . Biochemical Society Transactions , 33 (4): 643–645.

Price: Immunology and Infection Unit, Department of Biology, Hull York Medical School, University of York, Heslington, York YO10 5YW, UK.

13448 Ruan, J.P., Arhin, G.K., Ullu, E. & Tschudi, C., 2004. Functional characterization of a Trypanosoma brucei TATA-binding protein-related factor points to a universal regulator of transcription in trypanosomes. Molecular and Cellular Biology , 24 (21): 9610–9618.

Tschudi: Department of Epidemiology and Public Health, Yale University Medical School, 295 Congress Ave., New Haven, CT 06536-0812, USA. [christian.tschudi@yale.edu]

13449 Rubotham, J., Woods, K., Garcia-Salcedo, J.A., Pays, E. & Nolan, D.P., 2005. Characterization of two protein disulfide isomerases from the endocytic pathway of bloodstream forms of Trypanosoma brucei . Journal of Biological Chemistry , 280 (11): 10410–10418.

Nolan: Department of Biochemistry, Trinity College Dublin, Dublin 2, Ireland. [denolan@tcd.ie]

13450 Sant'Anna, C., Campanati, L., Gadelha, C., Lourenco, D., Labati-Terra, L., Bittencourt-Silvestre, J., Benchimol, M., Cunha-e-Silva, N.L. & De Souza, W., 2005. Improvement on the visualization of cytoskeletal structures of protozoan parasites using high-resolution field emission scanning electron microscopy (FESEM). Histochemistry and Cell Biology , 124 (1): 89–97.

De Souza: Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro CCS, Rio de Janeiro, bloco G, Cidade Universitária, 21949-900, Brazil.

13451 Schaap, P., 2005. Guanylyl cyclases across the tree of life. Frontiers in Bioscience , 10: 1485–1498.

Schaap: School of Life Sciences, University of Dundee, UK

13452 Schimanski, B., Nguyen, T.N. & Günzl, A., 2005. Characterization of a multisubunit transcription factor complex essential for spliced-leader RNA gene transcription in Trypanosoma brucei. Molecular and Cellular Biology , 25 (16): 7303–7313.

Günzl: Department of Genetics and Developmental Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-3710 USA. [gunzl@uchc.edu]

13453 Sharafeldin, A., Bittorf, T., Harris, R.A., Mix, E. & Bakhiet, M., 2004. Prolonged activation of transcription regulating factors in Trypanosoma brucei brucei nuclear proteins by interferon-γ stimulation. Acta Protozoologica , 43 (4): 373–377.

Sharafeldin: Centre for Infectious Medicine, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden. [Ahmed.Sharafeklin@cmm.ki.se]

13454 Sheader, K., Vaughan, S., Minchin, J., Hughes, K., Gull, K. & Rudenko, G., 2005. Variant surface glycoprotein RNA interference triggers a precytokinesis cell cycle arrest in African trypanosomes. Proceedings of the National Academy of Sciences of the United States of America , 102 (24): 8716–8721.

Rudenko: Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford OX1 3SY, United Kingdom. [gloria.rudenko@medawar.ox.ac.uk]

13455 Siegel, T.N., Tan, K.S.W. & Cross, G.A.M., 2005. Systematic study of sequence motifs for RNA trans splicing in Trypanosoma brucei . Molecular and Cellular Biology , 25 (21): 9586–9594.

Cross: Laboratory of Molecular Parasitology, The Rockefeller University, 1230 York Avenue, New York, NY 10021-6399, USA. [george.cross@ rockefeller.edu]

13456 Suzuki, T., Hashimoto, T., Yabu, Y., Majiwa, P.A.O., Ohshima, S., Suzuki, M., Lu ShaoHong, Hato, M., Kido, Y., Sakamoto, K., Nakamura, K., Kita, K. & Ohta, N., 2005. Alternative oxidase (AOX) genes of African trypanosomes: phylogeny and evolution of AOX and plastid terminal oxidase families. Journal of Eukaryotic Microbiology , 52 (4): 374–381.

Suzuki: Department of Molecular Parasitology, Nagoya City University, Graduate School of Medical Sciences, Kawasumi, Mizuho 467–8601 Nagoya, Japan.

13457 Tabel, H., Pan, W., Ogunremi, O., Wei, G. & Shi, M., 2006. CR3 (CD11b/CD18) is the major receptor for IgM antibody-mediated phagocytosis of African trypanosomes by macrophages: subsequent synthesis of TNF alpha; and nitric oxide are diversely affected. Molecular Immunology , 43 (1–2): 176.

Tabel: Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan, S7N 5B4, Canada. [tabel@sask.usask.ca]

13458 Taiwo, V.O., Olaniyi, M.O. & Ogunsanmi, A.O., 2003. Comparative plasma biochemical changes and susceptibility of erythrocytes to in vitro peroxidation during experimental Trypanosoma congolense and T. brucei infections in sheep. Israel Journal of Veterinary Medicine , 58 (4): 112–117.

Taiwo: Department of Veterinary Pathology, University of Ibadan, Ibadan, Nigeria.

13459 Toaldo, C.B., Kieft, R., Dirks-Mulder, A., Sabatini, R., van Luenen, H.G.A.M. & Borst, P., 2005. A minor fraction of base J in kinetoplastid nuclear DNA is bound by the J-binding protein 1. Molecular and Biochemical Parasitology , 143 (1): 111–115.

Borst: The Netherlands Cancer Institute, Division of Molecular Biology and Centre of Biomedical Genetics, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.

13460 van Luenen, H.G.A.M., Kieft, R., Mussmann, R., Engstler, M., ter Riet, B. & Borst, P., 2005. Trypanosomes change their transferrin receptor expression to allow effective uptake of host transferrin. Molecular Microbiology , 58 (1): 151–165.

Borst: The Netherlands Cancer Institute, Division of Molecular Biology and Centre for Biomedical Genetics, Plesmanlaan 121, 1060 CX Amsterdam, the Netherlands. [p.borst@nki.nl]

13461 van Weelden, S.W.H., van Hellemond, J.J., Opperdoes, F.R. & Tielens, A.G.M., 2005. New functions for parts of the Krebs cycle in procyclic Trypanosoma brucei , a cycle not operating as a cycle. Journal of Biological Chemistry , 280 (13): 12451–12460.

Tielens: Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands. [tielens@vet.uu.nl]

13462 Webb, H., Burns, R., Ellis, L., Kimblin, N. & Carrington, M., 2005. Developmentally regulated instability of the GPI-PLC mRNA is dependent on a short-lived protein factor. Nucleic Acids Research , 33 (5): 1503–1512.

Carrington: Department of Biochemistry, 80 Tennis Court Road, Cambridge CB2 1GA, UK. [mc115@cam.ac.uk]

13463 Webb, H., Burns, R., Kimblin, N., Ellis, L. & Carrington, M., 2005. A novel strategy to identify the location of necessary and sufficient cis-acting regulatory mRNA elements in trypanosomes. RNA , 11 (7): 1108–1116.

Carrington: Department of Biochemistry, 80 Tennis Court Road, Cambridge CB2 1GA, UK. [mc115@cam.ac.uk]

13464 Westergard, A.M. & Hutchings, N.R., 2005. Divalent cation control of flagellar motility in African trypanosomes. ISIS International Symposium on Int`erdisciplinary Science , 755: 153–158.

Westergard: Interdisciplinary Experimentation and Scholarship (IDEAS) Program, Department of Biological Science, Northwestern State University of Louisiana. Natchitoches, Louisiana 71497 USA.

13465 Wilkinson, S.R., Prathalingam, S.R., Taylor, M.C., Horn, D. & Kelly, J.M., 2005. Vitamin C biosynthesis in trypanosomes: A role for the glycosome. Proceedings of the National Academy of Sciences of the United States of America , 102 (33): 11645–11650.

Wilkinson: Department of Infection and Tropical Medicine, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.


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