ライフサイエンスコーパス: oocyst

1 osquito midgut interactions as it becomes an oocyst.

2 s essential for establishing polarity in the oocyst.

3 kinete, and differentiation from ookinete to oocyst.

4 raverse the mosquito midgut and transform to oocysts.

5 ment, oocysts attached onto already attached oocysts.

6 hilst also detecting damaged and/or excysted oocysts.

7 nd were infected with Cryptosporidium parvum oocysts.

8 trafficking mechanism to deliver PbSR to the oocysts.

9 les artificially spiked with Cryptosporidium oocysts.

10 to induce the excystation of Cryptosporidium oocysts.

11 d limiting the access of cattle to infective oocysts.

12 guts containing invading ookinetes and early oocysts.

13 ility to invade the mosquito midgut and form oocysts.

14 in, is expressed only in ookinetes and early oocysts.

15 possibility of distinguishing dead from live oocysts.

16 niform distribution on the surface in day 22 oocysts.

17 This technique had a detection limit of five oocysts.

18 notobiotic pigs were given 1-10 HuG1 or BoG2 oocysts.

19 teers challenged with Cryptosporidium parvum oocysts.

20 e and after a challenge with Cryptosporidium oocysts.

21 zoites, bradyzoites, and sporozoites but not oocysts.

22 oked infected meat, or by uptake of cat-shed oocysts.

23 in decreased infection relative to untreated oocysts.

24 ome amplification (WGA) of DNA from purified oocysts.

25 irds were challenged with live E. acervulina oocysts 14 days posthatch, and fecal-oocyst shedding and

26 After exposure to 100-3000 oocysts, 16 volunteers recorded, for a duration of 6 wee

27 Upon oocyst acquisition, these walls lose their integrity to

28 neity on transport of Cryptosporidium parvum oocyst and carboxylate microsphere in 2-dimensional micr

29 The robust oocyst and sporocyst walls protect the infective sporozo

30 ver they are severely deficient in ookinete, oocyst and sporozoite formation inside the mosquito vect

31 ased by 30% and 24% after infection with the oocyst and sporozoite stages of Plasmodium falciparum, r

32 development, fertilization, and ookinete-to-oocyst and sporozoite-to-liver stage transitions.

33 as secreted into the sporocyst cavity of the oocysts and after excystation, secretion was detected in

34 yptosporidium is transmitted by ingestion of oocysts and completes its life cycle in a single host.

35 asites lacking TRP1 failed to migrate within oocysts and did not egress, suggesting that TRP1 is a vi

36 RAW macrophages could interact rapidly with oocysts and engulfed them by remodelling of their actin

37 nt involves transformation of ookinetes into oocysts and formation of infective sporozoites.

38 or not DOC inhibits or promotes transport of oocysts and microspheres in agricultural soils and by ho

39 Transport of Cryptosporidium parvum oocysts and microspheres in two disparate (a clay- and F

40 CR to identify C. cayetanensis and C. parvum oocysts and microsporidia spores.

41 enes, protein expression is only reported in oocysts and sporozoites indicating that repressed transc

42 , which restored fertility and production of oocysts and sporozoites, which demonstrates that mitocho

43 A brief heat shock was applied to the oocysts and the nucleic acid purified using an optimized

44 e var gene is selected for expression in the oocyst, and transcription of this gene increases dramati

45 tidious nature, the passing of non-infective oocysts, and the short duration of oocyst shedding, dire

46 s in its feces and, after sporulation, these oocysts are infectious to cattle.

47 undantly expressed at a time when developing oocysts are observed, roughly 48 to 72 h after inoculati

48 reated parasites produced similar numbers of oocysts as controls.

49 ) patches for microspheres at pH 4.4 and for oocysts at pH 5.8 and 8.1, where the DLVO energy barrier

50 Sporozoites are formed within oocysts at the mosquito midgut wall and are released int

51 After initial attachment, oocysts attached onto already attached oocysts.

52 In the micromodel, oocysts attached to the forward portion of clean collect

53 hat surface charge heterogeneity allowed for oocyst attachment.

54 lood from DP-treated children (P = .06); the oocyst burden among mosquitoes was lower among those tha

55 The annual oocyst burden measured in community surveys is 3 to 434

56 le oocyst can possibly cause infection, this oocyst burden represents a major potential public health

57 eas of children might potentially reduce the oocyst burden.

58 lts in parasites that form normal numbers of oocysts, but fail to produce any sporozoites.

59 e host and thus the only source of infective oocysts, but other mammals and birds can develop tissue

60 nth eggs, Giardia cysts, and Cryptosporidium oocysts, but the UASB reactor system discharges higher c

61 e and chemistry of the wall of the T. gondii oocyst by combining wall surface treatments, fluorescenc

62 Effective removal of Cryptosporidium parvum oocysts by granular filtration requires the knowledge of

63 targets derived from Cryptosporidium parvum oocysts by the use of oligonucleotide-gold nanoparticles

64 Because a single oocyst can possibly cause infection, this oocyst burden

65 of 457 ookinete library clones and 652 early oocyst clones represented 175 and 346 unique expressed s

66 of transmission processes that amplified the oocyst concentration in the drinking-water effluent.

67 coprotein-coated microspheres best resembled oocyst concentration, despite having zeta similar to NH(

68 btain a 3-log inactivation of C. parvum Iowa oocysts, contact times of 105 and 128 min for a solution

69 usually become infected through ingestion of oocyst-contaminated soil and water, tissue cysts in unde

70 The first was that oocyst contamination of the drinking-water influent, cou

71 on were assessed by calculating the mosquito oocyst count as a marker for infectivity, using standard

72 pment and precipitation independently raised oocyst delivery to the ocean (average increases of 44% a

73 In contrast, NF166 and NF165 oocyst densities were strongly reduced in refractory mos

74 s and TEP1 silencing significantly increased oocyst densities.

75 genotyping, two loci significantly affecting oocyst density were identified: one on chromosome 2 betw

76 tor for attachment efficiencies of C. parvum oocyst deposition in porous media for a variety of envir

77 of suspended illite clay drastically enhance oocyst deposition.

78 s a method for confirming putative T. gondii oocysts detected in snail faeces and tissues by microsco

79 Oocysts developed extracellularly in a system whose esse

80 asexual blood forms, gametocytes, and in the oocysts developing inside mosquito mid-gut.

81 ctors of the complement-like system restores oocyst development and disease transmission to rodent ho

82 itoes that confer refractoriness (failure of oocyst development in mosquito midguts) to natural Plasm

83 s, MAb 1C3 markedly inhibited P. gallinaceum oocyst development in mosquito midguts.

84 mia that subsequently translated into higher oocyst development in mosquitoes.

85 ciparum, ookinete development in P. berghei, oocyst development in P. berghei and P. falciparum, and

86 fectious blood meals significantly inhibited oocyst development in the mosquito midgut.

87 D: +/- 1.80 nM) and dose-dependently blocked oocyst development in the mosquito with a 50% inhibitory

88 An antienolase antibody inhibits oocyst development of both Plasmodium berghei and Plasmo

89 tibodies against PfCelTOS strongly inhibited oocyst development of P. falciparum and Plasmodium bergh

90 Mosquito infection ensues upon oocyst development that follows ookinete invasion and tr

91 s RBC binding and plays an important role in oocyst development, a critical step in malaria transmiss

92 nts of the mosquito immune system that limit oocyst development, and provide insight into their possi

93 abolished the ability of those sera to block oocyst development.

94 he mosquito midgut epithelium or ookinete-to-oocyst differentiation but mediates a late-phase immune

95 ntify SOAP as a key molecule for ookinete-to-oocyst differentiation in mosquitoes.

96 we analyzed the ultrastructure of P.berghei oocyst differentiation in the wild type, recombinants th

97 d Anopheles stephensi genes expressed during oocyst differentiation on the midgut.

98 asexual stage genes was up-regulated during oocyst differentiation.

99 tious blood meal, at the time of ookinete to oocyst differentiation.

100 model was recorded to determine the attached oocyst distributions in transversal and longitudinal dir

101 reexisting indole levels in the gut join the oocyst dose and immune status as important factors that

102 Because of its oocyst durability Cryptosporidium parvum is a significan

103 rozoites, pointing to a role for PbSR in the oocyst during sporogony.

104 n-releated protein 1 (TRP1) is important for oocyst egress and salivary gland invasion, and hence for

105 ays chlorine inactivation of Cryptosporidium oocysts, emphasizing the need for additional pool remedi

106 nt across temperatures, counterbalancing the oocyst enhancement at 24 degrees C.

107 The genotype of the oocysts excreted in feces and the relative distribution

108 GloWPa-Crypto L1 is most sensitive to oocyst excretion rates, due to large variation reported

109 Oocyst excretion was assessed by enzyme-linked immunosor

110 ent per villus and significantly exacerbated oocyst excretion.

111 lts in intensified epithelial parasitism and oocyst excretion.

112 d be a cost-effective new tool for assessing oocyst filtration in porous media, for example, to evalu

113 estimated to be 300 oocysts for humans and 1 oocyst for the GKO mouse model.

114 ce were infected with Cryptosporidium parvum oocysts for 6-13 days and compared with uninfected contr

115 dian infectious dose was estimated to be 300 oocysts for humans and 1 oocyst for the GKO mouse model.

116 o WT parasites as reflected by impairment of oocyst formation and sporogonic development in the mosqu

117 Oocyst formation and sporozoite production, necessary fo

118 nsgene expression reduced Plasmodium berghei oocyst formation by 87% on average and greatly impaired

119 st gametocytes in vitro), completely blocked oocyst formation in a mouse model of transmission.

120 le gamete formation and completely prevented oocyst formation in female Anopheles stephensi mosquitoe

121 h kinetics compared to WT parasites; however oocyst formation in mosquitoes was reduced by 50 to 80%.

122 For successful oocyst formation newly formed ookinetes in the midgut lu

123 ant WT plasminogen to depleted serum rescues oocyst formation, recombinant inactive plasminogen does

124 en depletion leads to a strong inhibition of oocyst formation.

125 o gametocytes but have drastic impairment of oocyst formation.

126 Plasmodium sporozoites mature in oocysts formed in the mosquito gut wall and then invade

127 TU502 oocysts from different sources failed to infect gamma in

128 d to be at least about 10 oocysts/g (about 1 oocyst/g for a pica child) for Cryptosporidium, about 5

129 ), levels would need to be at least about 10 oocysts/g (about 1 oocyst/g for a pica child) for Crypto

130 high challenge doses (>1,000 and 300 to 500 oocysts) had higher RIs (RI = 5.57 [P = 0.027] and RI =

131 s of only 4 mg L(-1) SRHA and SDBS decreased oocyst hydrophobicity from 66% to 20% and from 66% to 5%

132 nsport of surface-treated, sterile C. parvum oocyst in porous media.

133 te is formed by budding from a multinucleate oocyst in the mosquito midgut.

134 e markedly impaired in their ability to form oocysts in Anopheles freeborni midguts.

135 idian parasites with morphologically similar oocysts in canine feces.

136 humans and animals, which is transmitted via oocysts in cat faeces or tissue cysts in contaminated me

137 n T. gondii forms cysts in vitro that induce oocysts in cats, the gold standard criterion for cysts.

138 rospheres may not be suitable surrogates for oocysts in certain types of soils.

139 exposure (as assessed by the mean number of oocysts in control mosquitoes) and antibody titers.

140 993 was attributed to Cryptosporidium parvum oocysts in drinking water.

141 and rapidly detecting Cryptosporidium parvum oocysts in environmental water, the authors developed a

142 By concentrating oocysts in faecal pellets, snails may facilitate entry o

143 udies in which genotyping of Cryptospiridium oocysts in feces of dogs and cats have been successful a

144 unexcysted (in vivo) Cryptosporidium parvum oocysts in human colonic adenocarcinoma (HCT-8) cells an

145 The domestic dog excretes oocysts in its feces and, after sporulation, these oocys

146 ocytes, PNP-deficient parasites did not form oocysts in mosquito midguts and were not transmitted fro

147 We imaged the release of sporozoites from oocysts in situ, which was preceded by active motility.

148 (69%) became ill, and 8 subjects (50%) shed oocysts in stool.

149 results in significantly elevated numbers of oocysts in susceptible and resistant mosquitoes.

150 ence of infected mosquitos at different mean oocysts in the control.

151 n maintaining the integrity of the T. gondii oocysts in the environment or after exposure to disinfec

152 Real time transport of oocysts in the micromodel was recorded to determine the

153 Sporozoites develop within oocysts in the mosquito midgut and then enter and mature

154 ilencing reduces the number of P. falciparum oocysts in the mosquito midgut by over 70% compared with

155 Plasmodium sporozoites develop within oocysts in the mosquito midgut wall and then migrate to

156 as measured by the number of Cryptosporidium oocysts in the stools) and also with the IL-1alpha conce

157 yotes (Canis latrans) can excrete N. caninum oocysts in their feces and that white-tailed deer (Odoco

158 vailable, and control focuses on eliminating oocysts in water supplies.

159 previously reported that Plasmodium berghei oocysts in which the CS gene is inactivated do not form

160 icrospheres achieved a superior match to the oocysts in zeta, concentration, mass recovery, and colli

161 of phagocytic cells in processing T. gondii oocysts, in line with non-classical routes of infection,

162 tro male gamete formation assays and reduced oocyst infection and prevalence in Anopheles mosquitoes.

163 train) gametocyte cultures slightly enhanced oocyst infection.

164 y addressed the effects of ClO2 on C. parvum oocyst infectivity in chlorinated recreational water ven

165 ted the relationship between % inhibition in oocyst intensity and % inhibition of prevalence of infec

166 pooled mosquitoes accurately quantifies mean oocyst intensity and generates comparable TRA estimates.

167 AlbB reduced malaria parasite prevalence and oocyst intensity at 28 degrees C.

168 er-assay variability of % inhibition of mean oocyst intensity at each concentration of 4B7 (lower con

169 l three IgGs showed 97 to 100% inhibition in oocyst intensity compared to control IgG.

170 anti-Pfs230, and anti-PfHAP2 IgGs inhibited oocyst intensity in a dose-dependent manner.

171 Luminescence-based estimates of oocyst intensity in individual mosquitoes should be inte

172 ffect on prevalence but a marked increase in oocyst intensity.

173 supporting sporozoite excystation following oocyst internalisation.

174 and measures that decrease spread of viable oocysts into the environment.

175 e assay for the detection of Cryptosporidium oocysts is described.

176 f the U.S. ranging from ca. 0.005 to ca. 0.5 oocysts/L.

177 itted by contamination of food or water with oocyst-laden feces from an infected animal.

178 er account for nearly a quarter of the total oocyst load, meaning that the developing world accounts

179 he effect of manure storage and treatment on oocyst loads using scenario analysis.

180 We find that although manure storage halves oocyst loads, manure treatment, especially of cattle man

181 development (day 1 after the blood meal) and oocyst maturation (day 7 after the blood meal) but not d

182 To date, only one apicomplexan oocyst membrane protein has been identified, Cryptospori

183 identification of parasite species using egg/oocyst morphology, which could overestimate parasite sha

184 l component of the events that precede intra-oocyst motility and subsequently sporozoite egress and s

185 In a C. parvum infection with 1 x 10(6) oocysts/mouse in SCID beige (SCIDbg) mice (SCID mice lac

186 ria protein expressed in ookinetes and young oocysts, named secreted ookinete adhesive protein (SOAP)

187 nexons resulted in an increase in Plasmodium oocyst number and infection prevalence.

188 , but not AGAP006241, caused an induction in oocyst number.

189 Differences in P. falciparum oocyst numbers between mosquito isofemale families fed o

190 s mosquitoes (approximately 90% reduction in oocyst numbers in the midgut).

191 Oocysts of C. parvum were isolated from environmental wa

192 e specific and sensitive detection of viable oocysts of Cryptosporidium parvum in environmental sampl

193 ged gnotobiotic piglets with equal number of oocysts of type 1 and type 2, given either simultaneousl

194 in-binding proteins and then develop into an oocyst on the midgut basal lamina.

195 develops and differentiates within parasite oocysts on the Anopheles mosquito midgut.

196 the ookinetes into the sporozoite-producing oocysts on the mosquito midgut wall.

197 viable in the mosquito midgut and never made oocysts or sporozoites, thereby abrogating transmission

198 ough targeted propagation in mice of progeny oocysts originating from populations lacking one parenta

199 s and associated microtubules underneath the oocyst outer membrane, which normally demarcate focal bu

200 As few as 10 oocysts per 300 microl of stools could be detected with

201 nsitivity was determined to be as low as 200 oocysts per gram of feces processed, equivalent to 2 ooc

202 per gram of feces processed, equivalent to 2 oocysts per PCR.

203 en measured in community surveys is 3 to 434 oocysts per square foot and is greater in areas where ca

204 . load from livestock manure of 3.2 x 10(23) oocysts per year.

205 fect, they are unable to progress beyond the oocyst phase of the parasite mosquito stage.

206 tein is a major type of surface protein that oocysts possess.

207 Oocyst production and mosquito infectivity is also signi

208 tly, triacsin C effectively reduced parasite oocyst production up to 88.1% with no apparent toxicity

209 in 1 minus parasites were fed to a mosquito, oocyst production was reduced by 70-90%, suggesting an i

210 DNA were achieved by a combination of three oocyst purification steps and whole-genome amplification

211 gly restricted the development of Plasmodium oocysts, reducing their number by 90%.

212 ites were observed in macrophages containing oocyst remnants or in new macrophages, giving rise to di

213 nate-capped silver-nanoparticle treatment of oocysts resulted in morphological modifications and decr

214 abelling of viable sporozoites excysted from oocysts reveals a complex admixture of surface proteins

215 y) than those ingesting low doses (30 to 100 oocysts; RI = 0.146).

216 w that watersheds with the highest levels of oocyst runoff align closely with regions of increased se

217 r detection limit was approximately 5 viable oocysts/sample for the assay procedure, including nuclei

218 n of food or water that is contaminated with oocysts shed by cats or by eating undercooked or raw mea

219 have focused attention on the importance of oocysts shed in the feces of infected cats.

220 the duration of both diarrhea (P<.0001) and oocyst shedding (P<.0001).

221 rvulina oocysts 14 days posthatch, and fecal-oocyst shedding and body weight gain were determined as

222 Fecal oocyst shedding and intestinal parasite burden were sign

223 with 3-1E protein showed significantly lower oocyst shedding and normal body weight gain than nonvacc

224 17, or -18 or IFN-gamma gene further reduced oocyst shedding compared with that achieved with 3-1E al

225 of 3-1E resulted in significantly decreased oocyst shedding compared with that in nonvaccinated chic

226 ice (SCID mice lacking functional NK cells), oocyst shedding was first demonstrated 18 days after inf

227 Duration of oocyst shedding was longer for human genotype than for z

228 bjects experiencing diarrhea with or without oocyst shedding, a trend toward a higher RI (P = 0.065)

229 ing parameters, including diarrhea severity, oocyst shedding, and overall health.

230 Fecal oocyst shedding, as well as intestinal parasite burden,

231 unocompromised mice and dramatically reduces oocyst shedding, diarrhea, and dehydration in neonatal c

232 infective oocysts, and the short duration of oocyst shedding, direct contact with cats is not thought

233 infection was monitored by quantifying fecal oocyst shedding.

234 asites suggesting a role for this protein in oocyst/sporozoite transmission to susceptible hosts.

235 ulation of at least 47 genes (upregulated in oocyst sporozoites [UOS genes]) before they infect the s

236 Although morphologically similar, oocyst sporozoites and salivary gland sporozoites differ

237 n, resulting in parasites capable of forming oocyst sporozoites but blocked in the salivary gland tra

238 Conversely, oocyst sporozoites show upregulation of at least 47 gene

239 he sporozoite secretory organelles, rendered oocyst sporozoites unable to infect the mosquito salivar

240 ed that SSP3 is expressed in mosquito midgut oocyst sporozoites, exhibiting an intracellular localiza

241 r microarray analysis shows that compared to oocyst sporozoites, salivary gland sporozoites upregulat

242 While oocyst sporulation rates of PbSR knockout parasites are

243 owever, progression from the ookinete to the oocyst stage and sporozoite formation were completely ab

244 reas TgROM2 and TgROM3 were expressed in the oocyst stage involved in transmission.

245 us protozoan parasite Toxoplasma gondii, the oocyst stage possesses a bilayered wall that protects th

246 ved organelle of the Plasmodium ookinete and oocyst stage required for sporogony-is dependent on the

247 also reveal an increased sugar uptake at the oocyst stage that decreased at the sporozoite stage of i

248 cidian parasites are transmitted via a fecal oocyst stage that is exceptionally resistant to environm

249 s for these losses by multiplying during the oocyst stage to form the infectious sporozoites.

250 to the mosquito-specific ookinete and young oocyst stages of the parasite.

251 eric repulsion and possibly other changes in oocyst surface properties.

252 e mosquito late-phase immune response limits oocyst survival are less understood.

253 nt immune mechanisms regulating ookinete and oocyst survival.

254 a late-phase immune response that decreases oocyst survival.

255 knockout parasites produce normal numbers of oocysts that fail to form sporozoites, pointing to a rol

256 ur column data confirm for freshly harvested oocysts that the presence of iron coatings on the sand m

257 Within the oocyst, the parasite multiplies into numerous sporozoite

258 Oocysts, the extremely hardy free-living environmental s

259 wall to digestive enzymes and the ability of oocysts to cause parenteral infections, the present stud

260 ith freshly harvested Cryptosporidium parvum oocysts to evaluate the effects of solution chemistry, s

261 es and discusses the inability of UV-exposed oocysts to regain infectivity.

262 Attachment of oocysts to silica surface in a radial stagnation point f

263 d as the sporozoites transit from the midgut oocysts to the salivary glands.

264 d from presumed storage organelles in day 15 oocysts to uniform distribution on the surface in day 22

265 After invasion ookinete-to-oocyst transition must occur, a process believed to requ

266 ia ookinetes and disappear after ookinete-to-oocyst transition.

267 ranular filtration requires the knowledge of oocyst transport and deposition mechanisms, which can be

268 ased on real time microscopic observation of oocyst transport in porous media.

269 hrough the temperate soil 5-fold, whereas no oocyst transport was detected in tropical soil.

270 SRHA had only a nominal effect in increasing oocysts transport in tropical soil, but caused a 6-fold

271 SDBS also increased oocysts transport through the temperate soil 5-fold, whe

272 the dissolved organic carbon (DOC), whereas oocysts transport was more affected by soil mineralogy.

273 sion of HSP70 mRNA in Cryptosporidium parvum oocysts via a simple heat shock process provides nonenzy

274 ffective in killing the parasite because the oocyst wall acts as a primary barrier to physical and ch

275 es to identify chemical factors that lead to oocyst wall disruption under physiological conditions.

276 ndings suggest a key biological role for the oocyst wall mechanics in maintaining the integrity of th

277 protein has been identified, Cryptosporidium oocyst wall protein 1 (COWP1).

278 polymorphism analysis of the Cryptosporidium oocyst wall protein gene for 134 of 136 (98.5%) samples

279 polymorphism analysis of the Cryptosporidium oocyst wall protein gene, direct sequencing of PCR fragm

280 analysis of the 18S rRNA and Cryptosporidium oocyst wall protein genes.

281 otein of Cryptosporidium and Cryptosporidium oocyst wall protein loci, while five isolates (all of wh

282 indentation measurements indicated that the oocyst wall resembles common plastic materials, based on

283 hesis that multiple COWPs play a role in the oocyst wall structure.

284 Given the resistance of the oocyst wall to digestive enzymes and the ability of oocy

285 OWP8 specifically localized to the C. parvum oocyst wall, supporting the hypothesis that multiple COW

286 fication of mRNA from as few as 30 C. parvum oocysts was demonstrated directly on-chip and compared t

287 infected with P. gallinaceum, the number of oocysts was dramatically reduced in midguts, and no spor

288 from as few as 5 x 10(3) purified C. parvum oocysts was successfully detected.

289 Internalised oocysts were associated to macrophage acidic compartment

290 g exposure to T. gondii-containing seawater, oocysts were detected by microscopy in snail faeces and

291 Nonviable oocysts were not detected.

292 l and sexual stages and the formation of new oocysts were observed during the course of infection.

293 Moreover, the majority of oocysts were retarded in their growth and were smaller i

294 d the same log reduction in concentration as oocysts, whereas results from unmodified microspheres de

295 al infection or abortion and by ingestion of oocysts, which, if it occurs during gestation, can also

296 , KN-93-treated parasites did not develop as oocysts, while KN-92-treated parasites produced similar

297 used to identify live and inactive C. parvum oocysts with over 90% certainty, whilst also detecting d

298 (mouse) model, we observed that treatment of oocysts with silver nitrate and proteinate-capped silver

299 t experiments determine the number of mature oocysts, without considering that different immune mecha

300 ch includes clays, and SRHA, both caused the oocysts zeta potential (zeta) to become more negative, b