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INDEX 487 Trypanosoma equiperdum, 90–1 glucose transporters, 144 Trypanosoma evansi,90 Trypanosoma rangeli, 174, 175 Trypanosoma vivax,91 chemotherapy, 419 variant surface glycoproteins (VSGs), 95, 96 vectors, 90 Trypanosomatids: amino acid uptake, 172 antigenic variation, 29–30, 89–90, 91–106 cell-cycle regulation, 76 chemotherapy, 446–53 drug resistance, 413–23 cyclic nucleotide signaling, 256 adenylyl cyclases, 259–60 functional aspects, 261–2 cyclin-dependent kinases (CDKs), 271–2 digestive organelles, 180 energy metabolism, 140–53 aldolase, 145–6 enolase, 148 glucose transport, 144 glucose-6-phosphate isomerase, 145 glyceraldehyde-3-phosphate dehydrogenase, 146–7 glycerol kinase, 147 glycerol transporter, 144 glycerol-3-phosphate dehydrogenase, 147 glycosomes, 140, 141 hexokinase, 144–5 hexose-monophosphate pathway, 149–51 metabolite transporters, 143–4 phosphofructokinase, 145 phosphoglycerate kinase, 147–8 phosphoglycerate mutase, 148 pyruvate kinase, 148 pyruvate phosphate dikinase, 148–9 pyruvate transporter, 144 therapeutic targets, 146–7 triose-phosphate isomerase, 146 genomes, 20–1, 73 immune response to infection, 103–4 innate resistance, 104–5 life cycles, 73–4, 180 mitochondria, 281 mitogen-activated protein (MAP) kinases, 269–70 ornithine decarboxylases, 189 post-transcriptional regulation, 73–85 effects of protein synthesis inhibition, 80 HSP genes, 80–1 therapeutic targeting, 86–7 translation control, 85 3-untranslated region, 76–80 procyclins (PARP proteins), 93 protein phosphatases, 274 purine metabolism, 212–15 transport, 203–5 pyrimidine metabolism, 220–1 RNA 5-untranslated region, 76 RNA cis-splicing, 75 RNA degradation, 84–5 RNA editing, 38–9 RNA polyadenylation, 75–6 RNA trans-splicing, 30, 33, 75–6 polycistronic RNA processing, 35–7, 49 surface coat: carbohydrates, 225–40 replacement during development, 93 structure, 91 transcription, 47, 48–50 class I genes, 50–6, 73 class II genes, 57 class III genes, 63 promoter structures, 52, 53 regulation, 51 spliced leader (SL) RNA genes, 59, 61–3 tRNA gene–small nuclear/small cytoplasmic RNA gene functional association, 62, 63–4 variant surface glycoproteins (VSGs), 30, 91–7 vectors, 90–1 Trypanosome alternative oxidase (ubiquinol:oxygen oxidoreductase), 141 inhibitors, 141, 143 Trypanosome lytic factor, 105 haptoglobin-related protein (Hpr), 105 Trypanothione, 192 biosynthesis inhibitors, 430 Leishmania drug resistance mechanisms, 415, 416 melarsoprol mode of action, 419 Trypanothione reductase, 419 Tsetse (Glossina), 90 Tubular system, nematodes, 336–7 TVCA1, 246 Tyrosine aminotransferase, 187 Tyrosine kinase, 370 Tyrosine phosphorylation–dephosphorylation, 265
488 INDEX U small nuclear RNA (snRNA) gene transcription, 59–60 tRNA gene functional association, 63 U2 snRNA gene transcription, 63 Ubiquinol:oxygen oxidoreductase, 141, 143 Ubiquinone (coenzyme Q), 161, 162 Ubiquitin, 73 Ubiquitin-conjugating enzymes, 73 unc-7, 376, 378 unc-9, 376, 378 unc-17, 368 unc-25, 372 unc-29, 371 unc-30, 372 unc-38, 371 unc-43, 372 unc-47, 372 unc-49, 372 Urate metabolism, 208, 209 Urea excretion, 171, 183 Urea metabolism, 208 Uredofs, 389 Ureotielic metabolism, 171 Uric acid excretion, 171 Uricotelic metabolism, 171 Uridine phosphoribosyltransferase (UPRT), 220, 221 Uridine phosphorylase (UP), 221, 222 Uridine-cytidine kinase (UK), 221 Vaccine candidacy tests, 18 var, 58, 107 regulation of expression, 107–8 Variant surface glycoproteins (VSGs), 91–7, 225, 226 antigenic variation, 30, 91, 226 expression regulation/switching, 99–102 genetic aspects, 97–103 role of telomeres, 100 switching, 102, 226 expression regulation, 99–102 function, 94 glycosylation sites, 226 glycosylphosphatidylinositol (GPI) anchors, 92–3, 96, 226 immune response, 226 potenital in vaccine development, 108 RNA trans-splicing, 30 structure, 92, 94–6, 226, 227 synthesis/secretion, 96–7 transcription regulation, 73, 78 see also VSG genes Vector-host systems, 7 Virulence factors, 17, 438 Leishmania, 111–22, 234, 235 protozoan proteinases, 180–1 VSG genes, 97 evolution, 102–3 expression sites (ES), 97–8 -amanitin-resistant transcription, 49, 50, 98 ESAG (expression site-associated genes), 97 promoter DNA-protein interactions, 54, 55 promoters, 53, 54, 97 regulation, 51, 97, 99–102 Whole chromosomes/whole genome shotgun sequencing, 11–13 WR99210, 409, 430 Wuchereria bancrofti, 457, 458 Xanthine oxidase, 209 Xanthine phosphoribosyltransferase (XPRT), 212, 213, 214 Yeast artificial chromosomes (YAC), 7, 8
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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
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414 DRUG RESISTANCE FIGURE 16.5 Str
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416 DRUG RESISTANCE FIGURE 16.6 Try
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418 DRUG RESISTANCE has permitted e
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420 DRUG RESISTANCE FIGURE 16.7 Dru
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422 DRUG RESISTANCE near future. Th
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424 DRUG RESISTANCE million new inf
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426 DRUG RESISTANCE some 50 million
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428 DRUG RESISTANCE pharynx, the bo
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430 DRUG RESISTANCE efforts for glo
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432 DRUG RESISTANCE and resistance
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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 and 478: 464 INDEX Aldolase, 143 Plasmodium
Page 479 and 480: 466 INDEX Ascofuranone, 143 ASCUT-1
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: 486 INDEX genome, 21 survey sequenc
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