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INDEX 465 Apicomplexans, 437 drug resistance, 399–413 energy metabolism, 154–69 carbohydrate storage, 166–8 developmental variation, 165–6 medical significance, 168–9 gene transcription, 58–9 genomes, 21–2 mitogen-activated protein (MAP) kinases, 268–9 plastids/apicoplasts, 287, 289, 290 therapeutic targeting, 292–3 protein phosphatases, 273–4 purine metabolism, 201–3, 209–12 pyrimidine metabolism, 219–20 RNA processing regulation, 85–6 Apicoplast, 288, 289 function, 291–2 origin, 289–91 protein targeting, 292 therapeutic targeting, 291, 292–3 APT, 197 Aqueporins, 322 nematodes, 326 Arabidopsis thaliana,13 Archezoa hypothesis, 283, 284 Arecoline, 388 Arginine: catabolism, 183–4 nitric oxide synthesis, 191 polyamines synthesis, 189–91 transport, 172–3 Arginine decarboxylase, 190 Aromatic amino acid catabolism, 187–8 Aromatic L--hydroxy acid dehydrogenase, 187, 188 Arsenicals, 419 resistance, 419–20 Artemisia annua, 411, 439 Artemisinin, 411, 439, 445 mode of action, 411 resistance, 411 Arthropod vectors, 74 African trypanosomes, 90 expressed sequence tag (EST) datasets, 9 genomes, 26 Leishmania, 112, 113 malaria control, 441 Artioposhtia triangulata, 392 Ascaridia galli, 353 Ascaris: genome, 24 size, 4, 20, 23 mitochondrial genomics, 25 proteinase inhibitors, 179 pyrimidine metabolism, 222 RNA trans-splicing, 33, 35 Ascaris lumbricoides, 360 chemotherapy, 456, 457 clinical aspects, 455 cuticle, 315 purine metabolism, 217 spliced leader (SL) RNA/U1 small nuclear RNA (snRNA) gene transcription, 60 Ascaris suum, 297, 312, 360 alimentary tract, 328, 329 defecation, 334 digestive processes, 329, 330 anatomy, 360, 362, 363 nervous system, 364–5 pharyngeal muscle, 364 cuticle, 313, 315, 316 drug absorption, 326, 327 energy metabolism, 339 developmental changes, 354, 355 glycogen, 340 glycolysis, 343, 344 mitochondria, 345, 346, 347–50, 351, 352, 353 excretion, 325, 326, 333 genome, 23 hydrostatic skeleton, 317, 321 inorganic ion transport, 319, 320–1, 332 life cycle, 311–12 muscle cells, 362–4 arm, 363–4 membrane potential, 365–6 muscle bag, 363 spindle, 362–3 neurophysiology, 365–6 acetylcholine receptors, 368, 371 cholinesterase, 366–7 FaRPs, 380, 381, 383 GABA, 372 glutamate, 373, 375 5-hydroxytryptamine, 378 nitric oxide, 384 neurotransmitters, 359, 366–84 nitric acid synthase, 191 nutrient absorption, 318, 330 osmoregulation, 321, 322, 331 tubular system, 336
466 INDEX Ascofuranone, 143 ASCUT-1, 315 Asparate transcarbamoylase (ATC), 218, 222 Aspartate aminotransferase, 182, 183 Aspartic proteinases, 174, 177, 178, 179, 180 Atovaquone, 440, 442, 444 mode of action, 162, 281, 440–1 resistance, 410–11, 412, 444 Atoxyl, 419 ATP generation: amitochondriate organisms, 127 Plasmodium falciparum, 160, 163 Trypanosomatidae, 141 AU rich elements (AREs), 72 Avermectins, 427 avr-14, 374, 375, 376 avr-15, 374, 375, 376, 377 Babesia, 437 chemotherapy, 446 genome, 21 purine transport, 203 tick vector genome, 26 Bacteria, genome size, 4 Bacterial artificial chromosomes (BAC), 7, 10 Bdelloura candida, 387–8, 392 Benznidazole, 414, 422, 446, 447 resistance, 422–3, 428 Bephenium, 368 Bioinformatics, genome dataset analysis, 14–17 Biomphalaria glabrata,26 BiP, 245 Bithionol, 458, 459 BLAST, 15, 16 BLASTX, 15 Bombesin-like neuropeptides, 320–1 Boophilus microplus,26 Bradynema, 328–9 Brugia malayi: chemotherapy, 457, 458 epicuticle, 313 genome, 23, 24–5 reference strain, 13 transcription factors, 59 Brugia pahangi: amino acid catabolism, 183 aqueporins, 322 cuticle, 315 drug absorption, 326, 327 purine metabolism, 217 Brugia timori, 457, 458 Butamisole, 368 Buthionine sulfoximine, 193, 430 Ca 2 -ATPase pumps, 246–7 Ca 2 -induced Ca 2 release (CICR), 247 Caenorhabditis briggsae,24 Caenorhabditis elegans, 298, 312 acetylcholine receptors, 368, 370, 371 alimentary tract, 328, 329, 335 defecation, 334 digestive processes, 330 aqueporins, 322 cuticle, 315, 316 dauer larvae, 354 drug resistance: anti-cholinesterase antihelmintics, 368 ivermectin, 376–7 levamisole, 371 mechanisms, 428 excretion, 324, 325, 326 genome, 4, 22–3, 24–5, 69 physical mapping, 8 glycogen metabolism, 340 inorganic ion transport, 319, 320–1, 332–3 mitochondrial genomics, 25 movement, 317 ‘uncs’, 321 neurophysiology: cholinesterase, 366 FaRPs, 380, 382, 383 GABAergic neurotransmission, 372 glutamate receptors, 373 glutamate-gated chloride channel subunits, 373–5, 376 5-hydroxytryptamine (5-HT), 378 neurotransmitters, 359 osmoregulation, 322, 323, 331–2, 336–7 P-glycoproteins (pgps), 333, 334 reference strain, 13 RNA trans-splicing, 30 polycistronic transcription units, 49 Calcium pumps, 246–7, 250 acidocalcisomes, 249 cestode tegument, 301 Calcium signaling, 242–56 Ca 2 amplitude oscillation, 242 Ca 2 properties, 242–3 Ca 2 sequestration mechanisms, 246–7 Ca 2 storage pool functions, 245 calcium binding proteins, see Calcium-binding proteins
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Molecular Medical Parasitology
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Molecular Medical Parasitology Edit
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Contents List of contributors Prefa
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List of contributors Mark Blaxter,
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LIST OF CONTRIBUTORS ix Richard. J.
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Preface Parasitology was born as th
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S E C T I O N I MOLECULAR BIOLOGY
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C H A P T E R 1 Parasite genomics M
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TABLE 1.1 Parasite genomes: genome
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GENERATING GENOMICS DATA 7 differen
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GENERATING GENOMICS DATA 9 TABLE 1.
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GENERATING GENOMICS DATA 11 called
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GENERATING GENOMICS DATA 13 200 000
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BIOINFORMATICS AND THE ANALYSIS OF
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THE POST-GENOMICS ERA, AND THE OTHE
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THE PARASITES AND THEIR GENOMES 19
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FURTHER READING 27 treated with a d
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C H A P T E R 2 RNA processing in p
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TRANS-SPLICING 31 cis trans Exon 1
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TRANS-SPLICING 33 snRNPs (small nuc
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TRANS-SPLICING 35 trans cis U2AF35
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RNA EDITING 37 P AAAA... AAAA... AA
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RNA EDITING 39 entire transcript re
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RNA EDITING 41 5 Editing block C Ed
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RNA EDITING 43 microscopy) approach
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FURTHER READING 45 Nilsen, T.W. (19
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C H A P T E R 3 Transcription Arthu
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UNUSUAL MODES OF TRANSCRIPTION IN T
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CLASS I TRANSCRIPTION IN TRYPANOSOM
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CLASS II TRANSCRIPTION OF PROTEIN C
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SL RNA AND U snRNA GENE TRANSCRIPTI
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FURTHER READING 65 and switching in
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C H A P T E R 4 Post-transcriptiona
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POST-TRANSCRIPTIONAL REGULATION IN
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FURTHER READING 87 inhibition, it m
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C H A P T E R 5 Antigenic variation
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ANTIGENIC VARIATION AT THE STRUCTUR
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ANTIGENIC VARIATION AT THE STRUCTUR
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VSG Signal sequence Amino-terminal
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GENETICS OF ANTIGENIC VARIATION 97
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IMMUNE RESPONSES TO TRYPANOSOME INF
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INNATE RESISTANCE, HUMAN SUSCEPTIBI
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ANTIGENIC VARIATION IN MALARIA 107
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FURTHER READING 109 ACKNOWLEDGEMENT
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C H A P T E R 6 Genetic and genomic
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‘FORWARD’ VS. ‘REVERSE’ GEN
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EXAMPLES OF ‘FORWARD’ GENETIC A
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EXAMPLES OF ‘FORWARD’ GENETIC A
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REVERSE GENETICS AND LEISHMANIA VIR
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VALIDATION OF CANDIDATE VIRULENCE G
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S E C T I O N II BIOCHEMISTRY AND C
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C H A P T E R 7 Energy metabolism P
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SUBCELLULAR ORGANIZATION OF AMITOCH
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CELL MEMBRANE Fructose [b] Glucose
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STEPS OF AMITOCHONDRIATE CORE METAB
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ENZYMATIC DIFFERENCES BETWEEN AMITO
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ACTION OF NITROIMIDAZOLE DRUGS 135
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ENVOI 137 unambiguously reflect the
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FURTHER READING 139 Saavedra-Lira,
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THE EMBDEN-MEYERHOF-PARNAS (EMP) PA
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WHY DO TRYPANOSOMATIDAE HAVE GLYCOS
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FURTHER READING 153 for use in agri
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CARBOHYDRATE METABOLISM 155 as a hu
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158 ENERGY METABOLISM - APICOMPLEXA
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172 PROTEIN METABOLISM PROTEINS (1)
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174 PROTEIN METABOLISM the C-termin
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176 PROTEIN METABOLISM and also, to
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178 PROTEIN METABOLISM values rangi
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180 PROTEIN METABOLISM of the plasm
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182 PROTEIN METABOLISM in vivo, in
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184 PROTEIN METABOLISM PROLINE Poly
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186 PROTEIN METABOLISM CO 2 Dec-SAM
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188 PROTEIN METABOLISM a cMDH has b
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190 PROTEIN METABOLISM Urea ARGININ
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192 PROTEIN METABOLISM been describ
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194 PROTEIN METABOLISM absence of g
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198 PURINES AND PYRIMIDINES enable
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200 PURINES AND PYRIMIDINES provide
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202 PURINES AND PYRIMIDINES activit
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204 PURINES AND PYRIMIDINES physiol
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206 PURINES AND PYRIMIDINES Amitoch
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208 PURINES AND PYRIMIDINES their a
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210 PURINES AND PYRIMIDINES FIGURE
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214 PURINES AND PYRIMIDINES protein
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220 PURINES AND PYRIMIDINES in Plas
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222 PURINES AND PYRIMIDINES whereas
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226 TRYPANOSOMATID CARBOHYDRATES AF
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228 TRYPANOSOMATID CARBOHYDRATES In
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230 TRYPANOSOMATID CARBOHYDRATES po
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232 TRYPANOSOMATID CARBOHYDRATES LP
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234 TRYPANOSOMATID CARBOHYDRATES re
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236 TRYPANOSOMATID CARBOHYDRATES sc
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A. sAP COOH [T][T](S/T)(S/T)(S/T)SS
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240 TRYPANOSOMATID CARBOHYDRATES Cr
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242 INTRACELLULAR SIGNALING protein
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244 INTRACELLULAR SIGNALING FIGURE
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246 INTRACELLULAR SIGNALING 212.5 2
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248 INTRACELLULAR SIGNALING cycle.
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250 INTRACELLULAR SIGNALING V-H -A
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252 INTRACELLULAR SIGNALING domain)
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254 INTRACELLULAR SIGNALING the kno
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256 INTRACELLULAR SIGNALING from in
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258 INTRACELLULAR SIGNALING FIGURE
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260 INTRACELLULAR SIGNALING ESAG4 (
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262 INTRACELLULAR SIGNALING and ind
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264 INTRACELLULAR SIGNALING ATPase
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266 INTRACELLULAR SIGNALING G11XG
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268 INTRACELLULAR SIGNALING a diffe
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270 INTRACELLULAR SIGNALING rapid l
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272 INTRACELLULAR SIGNALING cells w
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274 INTRACELLULAR SIGNALING PfPPJ i
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276 INTRACELLULAR SIGNALING is cont
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278 PLASTIDS, MITOCHONDRIA, AND HYD
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298 HELMINTH SURFACES Important exc
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300 HELMINTH SURFACES protease inhi
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302 HELMINTH SURFACES volume, there
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304 HELMINTH SURFACES projecting si
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306 HELMINTH SURFACES schistosome t
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308 HELMINTH SURFACES re-establish
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310 HELMINTH SURFACES hepatic cells
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312 HELMINTH SURFACES lungs. Larvae
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314 HELMINTH SURFACES cuticle, whic
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316 HELMINTH SURFACES cuticle in th
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318 HELMINTH SURFACES mec-8 or sym-
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320 HELMINTH SURFACES current, when
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322 HELMINTH SURFACES The cuticle-h
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324 HELMINTH SURFACES are typically
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326 HELMINTH SURFACES or carrier pr
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328 HELMINTH SURFACES of tyrosine-b
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330 HELMINTH SURFACES blood. The ge
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332 HELMINTH SURFACES Mutations in
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334 HELMINTH SURFACES in the hypode
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336 HELMINTH SURFACES (including H-
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338 HELMINTH SURFACES Blaxter, M.L.
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340 ENERGY METABOLISM IN HELMINTHS
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360 NEUROTRANSMITTERS CO 2 H NH 2 G
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362 NEUROTRANSMITTERS TABLE 15.1 An
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364 NEUROTRANSMITTERS more arms tha
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366 NEUROTRANSMITTERS the surroundi
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368 NEUROTRANSMITTERS proteins requ
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370 NEUROTRANSMITTERS FIGURE 15.11
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372 NEUROTRANSMITTERS FIGURE 15.13
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374 NEUROTRANSMITTERS sensitivity t
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376 NEUROTRANSMITTERS TABLE 15.3 Cl
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378 NEUROTRANSMITTERS crossed the c
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380 NEUROTRANSMITTERS have been tes
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382 NEUROTRANSMITTERS C-terminals a
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384 NEUROTRANSMITTERS Davis and Str
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386 NEUROTRANSMITTERS Cephalic gang
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388 NEUROTRANSMITTERS myoexcitation
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390 NEUROTRANSMITTERS is phosphoryl
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392 NEUROTRANSMITTERS many other an
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398 DRUG RESISTANCE of some of the
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400 DRUG RESISTANCE It is now estim
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402 DRUG RESISTANCE is again assume
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404 DRUG RESISTANCE An alternative
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406 DRUG RESISTANCE clinical eviden
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408 DRUG RESISTANCE FIGURE 16.4 Fol
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410 DRUG RESISTANCE Using similar s
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412 DRUG RESISTANCE whether these r
Page 427 and 428: 414 DRUG RESISTANCE FIGURE 16.5 Str
Page 429 and 430: 416 DRUG RESISTANCE FIGURE 16.6 Try
Page 431 and 432: 418 DRUG RESISTANCE has permitted e
Page 433 and 434: 420 DRUG RESISTANCE FIGURE 16.7 Dru
Page 435 and 436: 422 DRUG RESISTANCE near future. Th
Page 437 and 438: 424 DRUG RESISTANCE million new inf
Page 439 and 440: 426 DRUG RESISTANCE some 50 million
Page 441 and 442: 428 DRUG RESISTANCE pharynx, the bo
Page 443 and 444: 430 DRUG RESISTANCE efforts for glo
Page 445 and 446: 432 DRUG RESISTANCE and resistance
Page 447 and 448: 434 MEDICAL IMPLICATIONS TABLE 17.1
Page 449 and 450: 436 MEDICAL IMPLICATIONS TABLE 17.1
Page 451 and 452: 438 MEDICAL IMPLICATIONS transmissi
Page 453 and 454: 440 MEDICAL IMPLICATIONS H 2 C H H
Page 455 and 456: 442 MEDICAL IMPLICATIONS parasites
Page 457 and 458: 444 MEDICAL IMPLICATIONS neuropsych
Page 459 and 460: 446 MEDICAL IMPLICATIONS of toxic f
Page 461 and 462: 448 MEDICAL IMPLICATIONS Future con
Page 463 and 464: 450 MEDICAL IMPLICATIONS Melarsopro
Page 465 and 466: 452 MEDICAL IMPLICATIONS prevention
Page 467 and 468: 454 MEDICAL IMPLICATIONS resulting
Page 469 and 470: 456 MEDICAL IMPLICATIONS for S. ste
Page 471 and 472: 458 MEDICAL IMPLICATIONS are though
Page 473 and 474: 460 MEDICAL IMPLICATIONS FIGURE 17.
Page 475 and 476: 462 MEDICAL IMPLICATIONS Marr, J.J.
Page 477: 464 INDEX Aldolase, 143 Plasmodium
Page 481 and 482: 468 INDEX Cnidarians, RNA trans-spl
Page 483 and 484: 470 INDEX Entamoeba, 125 Ca 2 metab
Page 485 and 486: 472 INDEX Glucose-6-phosphate dehyd
Page 487 and 488: 474 INDEX Ivermectin, 398, 427, 455
Page 489 and 490: 476 INDEX Maduramicin, 412 Major va
Page 491 and 492: 478 INDEX Nitric oxide: neurotransm
Page 493 and 494: 480 INDEX calcium-binding proteins,
Page 495 and 496: 482 INDEX Pyrimidine transport, 200
Page 497 and 498: 484 INDEX Succinate:rhodoquinone ox
Page 499 and 500: 486 INDEX genome, 21 survey sequenc
Page 501: 488 INDEX U small nuclear RNA (snRN
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