bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential for Hepatitis C Virus Resistance to Nitazoxanide or Tizoxanide
Authors: Korba Brent E. , Elazar Menashe , Lui Ping , Rossignol Jean-François , Glenn Jeffrey S.
Published: August 2008

Nitazoxanide and its primary metabolite, tizoxanide, inhibit hepatitis C virus (HCV) replication in HCV replicon systems. To study the potential for resistance, we subjected Huh7 cells harboring HCV replicons to serial passage in 250 μM G418 and increasing concentrations of nitazoxanide or tizoxanide. Passage of the replicon-containing cell lines in either compound resulted in increases in the 50% effective concentrations (EC
50
s) (7- to 13-fold), EC
90
s (14- to 36-fold), and 50% cytotoxic concentrations (2- to 4-fold) of both compounds. Serial passage in either compound did not alter the susceptibility of HCV replicons to ribavirin or 2′-
C
-methylcytidine. Interestingly, serial passage in nitazoxanide or tizoxanide resulted in increased sensitivity to alpha interferon 2b: EC
50
s and EC
90
s were reduced three- and eightfold, respectively. Replicons isolated from these cell lines had no greater ability to confer tizoxanide resistance, or increased susceptibility to alpha interferon, than replicons isolated from the parental cell line that had not previously been exposed to nitazoxanide or tizoxanide. These findings are indicative of a cell-mediated activity differing from that of other anti-HCV drugs but complementary with interferon and are consistent with the enhanced response rates observed clinically when nitazoxanide is combined with pegylated interferon therapy. Finally, unlike data for other compounds in advanced clinical development for HCV, these data are consistent with resistance in HCV replicon-containing cell lines conferred by changes in the host and not by mutations in the virus.
Aspergillus fumigatus
Forms Biofilms with Reduced Antifungal Drug Susceptibility on Bronchial Epithelial Cells
Authors: Seidler Marc J. , Salvenmoser Stefanie , Müller Frank-Michael C.
Published: August 2008

Aspergillus fumigatus
is a leading cause of death in immunocompromised patients and a frequent colonizer of the respiratory tracts of asthma and cystic fibrosis (CF) patients. Biofilms enable bacteria and yeasts to persist in infections and can contribute to antimicrobial resistance. We investigated the ability of
A. fumigatus
to form biofilms on polystyrene (PS) and human bronchial epithelial (HBE) and CF bronchial epithelial (CFBE) cells. We developed a novel in vitro coculture model of
A. fumigatus
biofilm formation on HBE and CFBE cells. Biofilm formation was documented by dry weight, scanning electron microscopy (SEM), and confocal scanning laser microscopy (CSLM). The in vitro antifungal activities of seven antifungal drugs were tested by comparing planktonic and sessile
A. fumigatus
strains.
A. fumigatus
formed an extracellular matrix on PS and HBE and CFBE cells as evidenced by increased dry weight, SEM, and CSLM. These biofilms exhibited decreased antifungal drug susceptibility and were adherent to the epithelial cells, with fungi remaining viable throughout 3 days. These observations might have implications for treatment of
A. fumigatus
colonization in chronic lung diseases and for its potential impact on airway inflammation, damage, and infection.
Vibrio cholerae
O139 Multiple-Drug Resistance Mediated by
Yersinia pestis
pIP1202-Like Conjugative Plasmids
Authors: Pan Jing-Cao , Ye Rong , Wang Hao-Qiu , Xiang Hai-Qing , Zhang Wei , Yu Xin-Fen , Meng Dong-Mei , He Zhe-Sheng
Published: August 2008

A conjugative plasmid, pMRV150, which mediated multiple-drug resistance (MDR) to at least six antibiotics, including ampicillin, streptomycin, gentamicin, tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole, was identified in a
Vibrio cholerae
O139 isolate from Hangzhou, eastern China, in 2004. According to partial pMRV150 DNA sequences covering 15 backbone regions, the plasmid is most similar to pIP1202, an IncA/C plasmid in an MDR
Yersinia pestis
isolate from a Madagascar bubonic plague patient, at an identity of 99.99% (22,180/22,183 nucleotides). pMRV150-like plasmids were found in only 7.69% (1/13) of the O139 isolates tested during the early period of the O139 epidemic in Hangzhou (1994, 1996, and 1997); then the frequency increased gradually from 60.00% (3/5) during 1998 and 1999 to 92.16% (47/51) during 2000 to 2006. Most (42/51) of the O139 isolates bearing pMRV150-like plasmids were resistant to five to six antibiotics, whereas the plasmid-negative isolates were resistant only to one to three antibiotics. In 12 plasmid-bearing O139 isolates tested, the pMRV150-like plasmids ranged from approximately 140 kb to 170 kb and remained at approximately 1 or 2 copies per cell. High (4.50 × 10
−2
and 3.08 × 10
−2
) and low (0.88 × 10
−8
to 3.29 × 10
−5
) plasmid transfer frequencies, as well as no plasmid transfer (under the detection limit), from these O139 isolates to the
Escherichia coli
recipient were observed. The emergence of pMRV150-like or pIP1202-like plasmids in many bacterial pathogens and nonpathogens occupying diverse niches with global geographical distribution indicates an increasing risk to public health worldwide. Careful tracking of these plasmids in the microbial ecosystem is warranted.
Synthesis, Antimalarial Activity, and Intracellular Targets of MEFAS, a New Hybrid Compound Derived from Mefloquine and Artesunate
Authors: de Pilla Varotti Fernando , Botelho Ana Cristina C. , Andrade Anderson Assunção , de Paula Renata C. , Fagundes Elaine M. S. , Valverde Alessandra , Mayer Lúcia M. U. , Mendonça Jorge Souza , de Souza Marcus V. N. , Boechat Núbia , Krettli Antoniana Ursine
Published: August 2008

A new synthetic antimalarial drug, a salt derived from two antimalarial molecules, mefloquine (MQ) and artesunate (AS), here named MEFAS, has been tested for its pharmacological activity. Combinations of AS plus MQ hydrochloride are currently being used in areas with drug-resistant
Plasmodium falciparum
parasites; although AS clears parasitemia in shorter time periods than any other antimalarial drug, it does not cure infected patients; in addition, MQ causes side effects and is rather expensive, important problems considering that malaria affects mostly populations in poor countries. Here, we show that MEFAS is more effective than the combination of AS and MQ, tested in parallel at different mass proportions, against
P. falciparum
(chloroquine-resistant clone W2 and chloroquine-sensitive clone 3D7) in vitro and in mice infected with
Plasmodium berghei
, promoting cure of this infection. MEFAS tested against HepG2 hepatoma cells exhibited lower toxicity than the antimalarials AS and MQ alone or combined. Possible targets of MEFAS have been studied by confocal microscopy using fluorescent probes (Fluo-4 AM and BCECF-AM) in
P. falciparum
synchronous culture of W2-infected red blood cells. Dynamic images show that MEFAS exhibited intracellular action increasing cytoplasmic Ca
2+
at 1.0 ng/ml. This effect was also observed in the presence of tapsigargin, an inhibitor of SERCA, suggesting an intracellular target distinct from the endoplasmic reticulum. Trophozoites loaded with BCECF-AM, when treated with MEFAS, were still able to mobilize protons from the digestive vacuole (DV), altering the pH gradient. However, in the presence of bafilomycin A1, an inhibitor of the H
+
pump from acidic compartments of eukaryotic cells, MEFAS had no action on the DV. In conclusion, the endoplasmic reticulum and DV are intracellular targets for MEFAS in
Plasmodium
sp., suggesting two modes of action of this new salt. Our data support MEFAS as a candidate for treating human malaria.
Genomewide Expression Profiling of Cryptolepine-Induced Toxicity inSaccharomyces cerevisiae
Authors: Rojas Marta , Wright Colin W. , Piña Benjamin , Portugal José
Published: August 2008

We have used the budding yeastSaccharomyces cerevisiaeto identify genes that may confer sensitivity in vivo to the antimalarial and cytotoxic agent cryptolepine. FiveS. cerevisiaestrains, with different genetic backgrounds in cell permeability and DNA damage repair mechanisms, were exposed to several concentrations of cryptolepine. Cryptolepine showed a relatively mild toxicity for wild-type strains, which was augmented by either increasing cell permeability (Δerg6orISE2strains) or disrupting DNA damage repair (Δrad52strains). These results are compatible with the ability of cryptolepine to intercalate into DNA and thus promote DNA lesions. The effects of low concentrations of cryptolepine (20% and 40% inhibitory concentrations [IC20and IC40]) were analyzed by comparing the gene expression profiles of treated and untreated Δerg6yeast cells. Significant changes in expression levels were observed for 349 genes (117 upregulated and 232 downregulated). General stress-related genes constituted the only recognizable functional cluster whose expression was increased upon cryptolepine treatment, making up about 20% of upregulated genes. In contrast, analysis of the characteristics of downregulated genes revealed a specific effect of cryptolepine on genes related to iron transport or acid phosphatases, as well as a significant proportion of genes related to cell wall components. The effects of cryptolepine on the transcription of iron transport-related genes were consistent with a loss of function of the iron sensor Aft1p, indicating a possible disruption of iron metabolism inS. cerevisiae. Since the interference of cryptolepine with iron metabolism is considered one of its putative antimalarial targets, this finding supports the utility ofS. cerevisiaein drug-developing schemes.
In Vitro Antibacterial Activity of Vertilmicin and Its Susceptibility to Modifications by the Recombinant AAC(6′)-APH(2″) Enzyme
Authors: Li Cong-Ran , Yang Xin-Yi , Lou Ren-Hui , Zhang Wei-Xin , Wang Yue-Ming , Yuan Min , Li Yi , Chen Hui-Zhen , Hong Bin , Sun Cheng-Hang , Zhao Li-Xun , Li Zhuo-Rong , Jiang Jian-Dong , You Xue-Fu
Published: August 2008

Vertilmicin is a new semisynthetic aminoglycoside with a structure similar to that of netilmicin except for a methyl group at the C-6′ position. In the present study, the in vitro antibacterial activity of vertilmicin was studied, and its susceptibility to modifications by the recombinant aminoglycoside bifunctional modifying enzyme AAC(6′)-APH(2″) was compared with those of verdamicin and netilmicin. A total of 1,185 clinical isolates collected from hospitals in Beijing between 2000 and 2001 were subjected to the in vitro antibacterial activity evaluations, including MIC, minimum bactericidal concentration (MBC), and time-kill curve tests. The MICs were evaluated in non-gentamicin-resistant (gentamicin-susceptible and gentamicin-intermediate) strains and gentamicin-resistant strains, respectively. For most of the non-gentamicin-resistant bacteria (except for the isolates of
Pseudomonas
spp.), the MIC
90
s of vertilmicin were in the range of 0.5 to 8 μg/ml, comparable to those of the reference aminoglycosides. For the gentamicin-resistant isolates, the three semisynthetic aminoglycosides (vertilmicin, netilmicin, and amikacin) demonstrated low MIC
50
s and/or MIC
90
s, as well as high percent susceptibility values. Among the study drugs, vertilmicin showed the lowest MIC
90
s, 16 μg/ml, for the gram-positive gentamicin-resistant isolates of
Staphylococcus aureus
and
Staphylococcus epidermidis
. Meanwhile, vertilmicin was a potent bactericidal agent, with MBC/MIC ratios in the range of 1 to 2 for
Escherichia coli
,
Klebsiella pneumoniae
, and
S. aureus
and 1 to 4 for
S. epidermidis
. The time-kill curve determination further demonstrated that this effect was rapid and concentration dependent. In evaluations of susceptibility to modifications by the recombinant AAC(6′)-APH(2″) with maximum rate of metabolism/

K
m

measurements, vertilmicin exhibited susceptibilities to both acetylation and phosphorylation lower than those of netilmicin and verdamicin.
Identification and Characterization of Two Novel Staphylococcal Enterotoxins, Types S and T
Authors: Ono Hisaya K. , Omoe Katsuhiko , Imanishi Ken'ichi , Iwakabe Yoshihiro , Hu Dong-Liang , Kato Hidehito , Saito Naoyuki , Nakane Akio , Uchiyama Takehiko , Shinagawa Kunihiro
Published: August 2008

In addition to two known staphylococcal enterotoxin-like genes (seljandselr), two novel genes coding for two superantigens, staphylococcal enterotoxins S and T (SES and SET), were identified in plasmid pF5, which is harbored by food poisoning-relatedStaphylococcus aureusstrain Fukuoka 5. This strain was implicated in a food poisoning incident in Fukuoka City, Japan, in 1997. Recombinant SES (rSES) specifically stimulated human T cells in a T-cell receptor Vβ9- and Vβ16-specific manner in the presence of major histocompatibility complex (MHC) class II+antigen-presenting cells (APC). rSET also stimulated T cells in the presence of MHC class II+APC, although its Vβ skewing was not found in reactive T cells. Subsequently, we examined the emetic activity of SES and SET. We also studied SElR to determine emetic activity in primates. This toxin was identified in previous studies but was not examined in terms of possession of emetic activity for primates. rSES induced emetic reactions in two of four monkeys at a dose of 100 μg/kg within 5 h of intragastric administration. In one monkey, rSET induced a delayed reaction (24 h postadministration) at a dose of 100 μg/kg, and in the other one, the reaction occurred 5 days postadministration. rSElR induced a reaction in two of six animals within 5 h at 100 μg/kg. On this basis, we speculate that the causative toxins of vomiting in the Fukuoka case are SES and SER. Additionally, SES, SER, and SET also induced emesis in house musk shrews as in the monkeys.
Total, Membrane, and Immunogenic Proteomes of Macrophage- and Tick Cell-Derived
Ehrlichia chaffeensis
Evaluated by Liquid Chromatography-Tandem Mass Spectrometry and MALDI-TOF Methods
Authors: Seo Gwi-Moon , Cheng Chuanmin , Tomich John , Ganta Roman R.
Published: August 2008

Ehrlichia chaffeensis
, a tick-transmitted rickettsial, is the causative agent of human monocytic ehrlichiosis. To examine protein expression patterns, we analyzed total, membrane, and immunogenic proteomes of
E. chaffeensis
originating from macrophage and tick cell cultures. Total proteins resolved by one-dimensional gel electrophoresis and subjected to liquid chromatography-electrospray ionization ion trap mass spectrometry allowed identification of 134 and 116 proteins from macrophage- and tick cell-derived
E. chaffeensis
, respectively. Because a majority of immunogenic proteins remained in the membrane fraction, individually picked total and immunogenic membrane proteins were also surveyed by liquid chromatography-tandem mass spectrometry and matrix-assisted laser desorption ionization-time of flight methods. The analysis aided the identification of 48 additional proteins. In all, 278 genes of the
E. chaffeensis
genome were verified as functional genes. They included genes for DNA and protein metabolism, energy metabolism and transport, membrane proteins, hypothetical proteins, and many novel proteins of unknown function. The data reported in this study suggest that the membrane of
E. chaffeensis
is very complex, having many expressed proteins. This study represents the first and the most comprehensive analysis of
E. chaffeensis
-expressed proteins. This also is the first study confirming the expression of nearly one-fourth of all predicted genes of the
E. chaffeensis
genome, validating that they are functionally active genes, and demonstrating that classic shotgun proteomic approaches are feasible for tick-transmitted intraphagosomal bacteria. The identity of novel expressed proteins reported in this study, including the large selection of membrane and immunogenic proteins, will be valuable in elucidating pathogenic mechanisms and developing effective prevention and control methods.
PapX, a P Fimbrial Operon-Encoded Inhibitor of Motility in Uropathogenic
Escherichia coli
Authors: Simms Amy N. , Mobley Harry L. T.
Published: August 2008

Motility and adherence are two integral aspects of bacterial pathogenesis. Adherence, often mediated by fimbriae, permits bacteria to attach to host cells and establish infection, whereas flagellum-driven motility allows bacteria to disseminate to sites more advantageous for colonization. Both fimbriae and flagella have been proven important for virulence of uropathogenic
Escherichia coli
(UPEC). Reciprocal regulation is one mechanism by which bacteria may reconcile the contradictory actions of adherence and motility. PapX, a P fimbrial gene product of UPEC strain CFT073, is a functional homolog of MrpJ of
Proteus mirabilis
; ectopic expression of
papX
in
P. mirabilis
reduces motility. To define the connection between P fimbria expression and motility in UPEC, the role of
papX
in the regulation of motility of strain CFT073 was examined. Overexpression of
papX
decreased motility of CFT073, which correlated with both a significant reduction in flagellin protein synthesized and flagella assembled on the cell surface. Conversely, an increase in motility and flagellin production was seen in an isogenic
papX
deletion mutant of CFT073. Microarray and quantitative reverse transcription-PCR analysis indicated that repression of motility of CFT073 by PapX appears to occur at the transcriptional level; expression of many motility-associated genes, including
flhDC
, the master regulator of motility, is decreased when
papX
is overexpressed. Transcription of motility genes is increased in the
papX
mutant compared to wild type. Electrophoretic mobility gel shift analysis revealed that PapX binds to the
flhD
promoter. We conclude that synthesis of P fimbriae regulates flagellum synthesis to repress motility via PapX.
ADP-Ribosylation of Actin by theClostridium botulinumC2 Toxin in Mammalian Cells Results in Delayed Caspase-Dependent Apoptotic Cell Death
Authors: Heine Karin , Pust Sascha , Enzenmüller Stefanie , Barth Holger
Published: August 2008

The binary C2 toxin fromClostridium botulinummono-ADP-ribosylates G-actin in the cytosol of eukaryotic cells. This modification leads to depolymerization of actin filaments accompanied by cell rounding within 3 h of incubation but does not immediately induce cell death. Here we investigated the long-term responses of mammalian cell lines (HeLa and Vero) following C2 toxin treatment. Cells stayed round even though the toxin was removed from the medium after its internalization into the cells. No unmodified actin reappeared in the C2 toxin-treated cells within 48 h. Despite actin being completely ADP-ribosylated after about 7 h, no obvious decrease in the overall amount of actin was observed for at least 48 h. Therefore, ADP-ribosylation was not a signal for an accelerated degradation of actin in the tested cell lines. C2 toxin treatment resulted in delayed apoptotic cell death that became detectable about 15 to 24 h after toxin application in a portion of the cells. Poly(ADP)-ribosyltransferase 1 (PARP-1) was cleaved in C2 toxin-treated cells, an indication of caspase 3 activation and a hallmark of apoptosis. Furthermore, specific caspase inhibitors prevented C2 toxin-induced apoptosis, implying that caspases 8 and 9 were activated in C2 toxin-treated cells. C2I, the ADP-ribosyltransferase component of the C2 toxin, remained active in the cytosol for at least 48 h, and no extensive degradation of C2I was observed. From our data, we conclude that the long-lived nature of C2I in the host cell cytosol was essential for the nonreversible cytotoxic effect of C2 toxin, resulting in delayed apoptosis of the tested mammalian cells.
Coinfection with the Intestinal NematodeHeligmosomoides polygyrusMarkedly Reduces Hepatic Egg-Induced Immunopathology and Proinflammatory Cytokines in Mouse Models of Severe Schistosomiasis
Authors: Bazzone Lindsey E. , Smith Patrick M. , Rutitzky Laura I. , Shainheit Mara G. , Urban Joseph F. , Setiawan Tommy , Blum Arthur M. , Weinstock Joel V. , Stadecker Miguel J.
Published: August 2008

Infection with the trematode helminthSchistosoma mansoniresults in a parasite egg-induced, CD4 T-cell-mediated, hepatointestinal granulomatous and fibrosing inflammation that varies greatly in severity, with a higher frequency of milder forms typically occurring in regions where the disease is endemic. One possible explanation for this is that in these regions the degree of inflammation is lessened by widespread concurrent infection with gastrointestinal nematodes. We tested this hypothesis by establishing a murine coinfection model in which mice were infected with the intestinal nematode parasiteHeligmosomoides polygyrusprior to infection withS. mansoni. In CBA mice that naturally display a severe form of schistosomiasis, preinfection withH. polygyrusresulted in a marked reduction in schistosome egg-induced hepatic immunopathology, which was associated with significant decreases in the levels of interleukin-17 (IL-17), gamma interferon, tumor necrosis factor alpha, IL-23, IL-6, and IL-1β and with increases in the levels of IL-4, IL-5, IL-10, and transforming growth factor β in mesenteric lymph node cells, purified CD4 T cells, and isolated liver granuloma cells. There also were increases in liver Ym1 and forkhead box P3 transcription factor expression. In another model of high-pathology schistosomiasis induced in C57BL/6 mice by immunization with schistosome egg antigens in complete Freund's adjuvant, coinfection with the nematodes also resulted in a marked inhibition of hepatic immunopathology accompanied by similar shifts in cytokine production. These findings demonstrate that intestinal nematodes prevent Th1- and Th17-cell-mediated inflammation by promoting a strong Th2-polarized environment associated with increases in the levels of alternatively activated macrophages and T regulatory cells, which result in significant amelioration of schistosome-induced immunopathology.
Modulation of Acute Diarrheal Illness by Persistent Bacterial Infection
Authors: McBee Megan E. , Zheng Patricia Z. , Rogers Arlin B. , Fox James G. , Schauer David B.
Published: August 2008

Acute diarrheal illness is a global health problem that may be exacerbated by concurrent infection. Using
Citrobacter rodentium
, a murine model of attaching and effacing diarrheagenic
Escherichia coli
, we demonstrate that persistent
Helicobacter hepaticus
infection modulates host responses to diarrheal disease, resulting in delayed recovery from weight loss and from tissue damage. Chronic colitis in concurrently infected mice is characterized by macrophage and Foxp3
+
regulatory T-cell accumulation. Prolonged disease is also associated with increased interleukin-17 expression, which may be due to suppression of gamma interferon during the acute phase of diarrheal infection. This new model of polymicrobial infection provides insight into the mechanism by which subclinical infection can exacerbate morbidity due to an unrelated self-limiting infection.
Enhanced Toll-Like Receptor Responsiveness Associated with Mitogen-Activated Protein Kinase Activation in
Plasmodium falciparum
-Infected Children
Authors: Hartgers Franca C. , Obeng Benedicta B. , Voskamp Astrid , Larbi Irene A. , Amoah Abena S. , Luty Adrian J. F. , Boakye Daniel , Yazdanbakhsh Maria
Published: August 2008

Acute
Plasmodium falciparum
infection is associated with strongly upregulated cytokine responses that are at least partly the result of activation of Toll-like receptors (TLRs). Whether and how TLR expression/responsiveness changes upon malarial infection is, however, currently not well understood. To assess this, we examined expression of TLRs and used the TLR ligand lipopolysaccharide (LPS) and Pam
3
Cys to stimulate peripheral blood mononuclear cells (PBMCs) from Ghanaian schoolchildren who live in a rural area where
P. falciparum
is endemic. Expression of TLR2 was higher, and responses to its ligand, Pam
3
Cys, were enhanced in
P. falciparum
-infected children compared to their uninfected counterparts. In cells from the same children, stimulation by Pam
3
Cys resulted in higher p38 mitogen-activated protein kinase activation and higher cytokine production. In vitro experiments confirmed that preincubation of PBMCs with
P. falciparum
-infected red blood cells enhanced responsiveness to TLR ligands. Taken together, the data indicate that
P. falciparum
-infected children in areas where malaria is endemic have an altered innate immune system, which might be important for the balance between immunity and pathology when new infections are encountered or when novel vaccines are introduced.
Identification and Characterization of the
Plasmodium yoelii
PyP140/RON4 Protein, an Orthologue of
Toxoplasma gondii
RON4, Whose Cysteine-Rich Domain Does Not Protect against Lethal Parasite Challenge Infection
Authors: Narum David L. , Nguyen Vu , Zhang Yanling , Glen Jacqueline , Shimp Richard L. , Lambert Lynn , Ling Irene T. , Reiter Karine , Ogun Solabomi A. , Long Carole , Holder Anthony A. , Herrera Raul
Published: August 2008

Previously, we identified a
Plasmodium yoelii
YM 140-kDa merozoite protein, designated PyP140, which formed a complex with apical membrane antigen 1 (AMA1). Furthermore, we produced a nonprotective monoclonal antibody (MAb), 48F8, that immunoprecipitated metabolically labeled PyP140 and localized the protein to the merozoite's apical end and, less frequently, to the merozoite surface, as observed by immunofluorescence assay (IFA). Here, using MAb 48F8, we have identified the
pyp140
gene by screening a
P. yoelii
λ-Zap cDNA expression library. The
pyp140
cDNA covers approximately 90% of the putative open reading frame (ORF) of PY02159 from the
P. yoelii
NL genome sequencing project. Analysis of the complete gene identified the presence of two introns. The ORF encodes a 102,407-Da protein with an amino-terminal signal sequence, a series of three unique types of repeats, and a cysteine-rich region. The binding site of MAb 48F8 was also identified. A BLAST search with the deduced amino acid sequence shows significant similarity with the
Toxoplasma gondii
RON4 protein and the
Plasmodium falciparum
RON4 protein, and the sequence is highly conserved in other
Plasmodium
species. We produced the cysteine-rich domain of PyP140/RON4 by using the
Pichia pastoris
expression system and characterized the recombinant protein biochemically and biophysically. BALB/c mice immunized with the protein formulated in oil-in-water adjuvants produced antibodies that recognize parasitized erythrocytes by IFA and native PyP140/RON4 by immunoblotting but failed to protect against a lethal
P. yoelii
YM infection. Our results show that PyP140/RON4 is located within the rhoptries or micronemes. It may associate in part with AMA1, but the conserved cysteine-rich domain does not appear to elicit inhibitory antibodies, a finding that is supported by the marked sequence conservation in this protein within
Plasmodium
spp., suggesting that it is not under immune pressure.
The effects of an addition of force-free particles on the rheological properties of fine suspensions
Authors: Coussot Philippe , Piau Jean-Michel
Published: August 2008

This study provides some elements for understanding the behavior of water–debris mixtures containing clay, silt, sand, and boulders at high solid concentrations. Accurate, simple shear rheometrical results for various clay–water mixtures and fine debris flow fractions with different added sand concentrations, in the shear rate range from 10−2to 10−2 s−1are presented. In this shear rate range, the behavior of these fluids is similar to the behavior of the initial fluid (without sand), i.e., it may be well represented by a Herschel–Bulkley model (with a power parameter close to 1/3). With the initial fluids (yield stress from 20 to 200 Pa) the suspension yield stress increases exponentially with the increase in sand (diameter between 100 and 200 μm) concentration, as long as the latter does not exceed 30%. However the rate of increase is less than the corresponding rate for the initial fluid and is correspondingly smaller as the grain size distribution is less well sorted. Diagrams showing the increase of yield stress with solid concentration may help to estimate the yield stress of coarser suspensions as long as the solid fraction is not too close to the maximum packing fraction. Key words : clay–water suspensions, water–debris mixtures, rheology, yield stress, sand addition, rheometry.
Modélisation en centrifugeuse du comportement d'un pieu flexible chargé horizontalement à proximité d'un talus
Authors: Bouafia Ali , Bouguerra Ahmed
Published: August 2008

This paper presents the results of a static lateral loading test, carried out in a centrifuge, on the reduced model of a single pile, instrumented with strain gauges, installed near a dense sandy slope. The effect of the proximity of the slope on the behaviour of the pile is studied. P–Y lateral reaction curves are constructed, and the variations of the horizontal subgrade modulus are analyzed. A practical method, based on the correction of the horizontal soil P–Y curves, is proposed to study the behaviour of piles near a slope. Key words : horizontal loading, pile, centrifuge, slope, sand, P–Y curve.
Strength of frozen saline soils
Authors: Hivon E.G. , Sego D.C.
Published: August 2008

This paper summarizes an extensive laboratory program undertaken to study the influence of soil type, temperature, and salinity on the strength of three different frozen soils under conditions of unconfined constant strain rate tests. Since the effects of temperature and salinity can be unified by studying the variation of unfrozen water content, measurements of unfrozen water at different temperatures were carried out using the time-domain reflectometry (TDR) method. The stress–strain behavior is influenced by the presence of fine particles in the soil, and an increase in temperature and salinity (unfrozen water content) causes a significant loss of strength. For each soil tested, a predictive model of its strength in terms of salinity and temperature (unfrozen water content) is presented. Key words : frozen soil, saline, unfrozen water, strength.
Grouted-in installation of piezometers in boreholes
Authors: McKenna Gordon T.
Published: August 2008

Because a modern diaphragm-type piezometer tip only requires a small change in fluid volume for pressure equalization, the conventional, large sand intake zone around the piezometer tip can be omitted, and the tip can be grouted in a borehole with cement–bentonite grout. This grouted-in installation method allows simpler and easier installation, accurate readings, fast response to changing formation pore-water pressures, installation in boreholes shared with other geotechnical instruments, and can save 10–75% on the installation cost of a piezometer. The grouted-in installation method can be used for most soil conditions provided that the grout is less permeable than the formation. A theoretical basis for the grouted-in installation method is presented with supporting laboratory and field data from the Syncrude Canada Ltd. oil sands mine. Key words : piezometer, grout, instrumentation, hydraulic conductivity, hydrodynamic time lag, oil sands.
Influence of loading rate on the capacity of a model pile in clay
Authors: Horvath Robert G.
Published: August 2008

Loading tests were carried out on a model pile embedded in clay to examine the influence of rate of loading on the capacity of the pile. The pile was loaded to failure using constant rate of penetration (CRP), quick maintained loading (QML), and quick continuous loading (QCL) methods of loading. The QCL test models the Statnamic loading test, which has been recently developed in Canada. The CRP tests were used as a reference, and the results were normalized using the CRP test results. The durations of the QML and QCL tests varied from approximately 0.1 s to 17 min, which are significantly faster than normal loading rates. Applied loads and point load were measured using load cells, and top displacement was measured using a displacement transducer. The test results showed an increase in pile capacity with increased rate of loading. Damping was found to be significant for the QCL tests (duration = 0.1 s) and negligible for the QML tests (duration ≥ 10 s). Correcting the results of the QCL tests for damping, using the equilibrium point method developed for Statnamic testing, greatly improved the correlation of the QCL and QML test results. Key words : model piles, axial loading, loading rate, clay, laboratory study, test methods.
ON THE NEMATODE GENUS RHABDOCHONA RAILLIET, 1916 (NEMATODA: SPIRUROIDEA)
Authors: Choquette L. P. E.
Published: August 2008

The systematic position of the genus Rhabdochona Railliet, 1916 and its diagnosis is reviewed. The genus comprising 33 species has a world-wide distribution and has been found, with one exception, in fish. Species from fish in North America are discussed and R. cascadilla Wigdor, 1918 is redescribed; R. laurentiana Lyster, 1940 is considered to be identical with the latter. A new species, R. milleri, is described. A host list and the geographical distribution of the 33 species of Rhabdochona so far recorded are given.
THE EFFECT OF INSECTICIDES ON THE HEARTBEAT OF PERIPLANETA
Authors: Orser W. B. , Brown A. W. A.
Published: August 2008

The effect of nine insecticidal compounds upon the rate of heartbeat of the American cockroach was ascertained by their injection into adult male insects at a dosage of 80 μgm. per individual, corresponding to 100 mgm. per kgm. body weight. The chlorinated hydrocarbons DDT, lindane, chlordane, and toxaphene exerted little effect, the maximum response being a slight acceleration. The dinitro compounds DNOC and DNCHP caused an increase in rate, followed by total failure of the heart. Parathion and thiocyanoethyl laurate proved to be slightly stimulatory in the concentrations employed. Rotenone steadily depressed the rate of heartbeat until it stopped. Similar effects were produced by applying the insecticide in a contact spray in benzene-kerosene mixture, although the solvent caused an initial drop in heart rate that was probably associated with temporary narcosis. The heart of decapitated insects showed a gradual decrease in pulsation rate and was less sensitive to the effects of insecticides.
THE EFFECT OF COLD UPON THE CONCENTRATION OF VITAMIN C IN THE OOCYTES OF ARION SUBFUSCUS AND DEROCERAS RETICULATUM
Authors: Watts Anne H. G.
Published: August 2008

Slugs of the species Arion subfuscus and Deroceras reticulatum were exposed to a temperature of 2 °C. for periods ranging from 10 to 109 days. The vitamin C content of their primary oocytes as revealed by Bourne's two methods was found to be greater than that observed in controls kept at room temperature. The difference became apparent after 10 to 21 days of exposure and was maintained until the 45th to 50th day. After this time the level of vitamin C in the oocytes of the cold animals dropped again to normal, or even below, as the slugs aged and died.
SELECTION FOR DDT TOLERANCE IN A BENEFICIAL PARASITE, MACROCENTRUS ANCYLIVORUS ROH.: I. SOME SURVIVAL CHARACTERISTICS AND THE DDT RESISTANCE OF THE ORIGINAL LABORATORY STOCK
Authors: Pielou D. P. , Glasser R. F.
Published: August 2008

Macrocentrus ancylivorus Roh. is a short-lived insect, a fact which must be taken into account in any experimental work on this species. Well fed females have a mean life of about five days. In the absence of food, but in the presence of water, this period is reduced to one and one-half days. In the absence of water and in dry air it is not much further decreased; adequate nutrition seems to be the main survival factor. Exposure of young adults to films of crystalline DDT in celloidin, for a few minutes, results in a heavy initial mortality with the toxic action completed within 40 hr., subsequent deaths being due to natural mortality. In all experiments males were more susceptible than females. In view of the short life of the insect, the results can be conveniently expressed in survival, or longevity, curves; these show the quantitative effects of the DDT in destroying part of, and in affecting the natural decline of, the experimental populations. Examination of the death rate among the tail of survivors of such DDT treatments shows that destruction has been selective, and that these insects die more slowly than those in the controls.
OBSERVATIONS ON THE BIOLOGY OF THE INFECTIVE LARVAE OF STRONGYLOIDES AGOUTII
Authors: Reesal Michael R.
Published: August 2008

The larvae of Strongyloides agoutii are positively thermotactic, are stimulated by light, and although not actively attracted by it, remain in lighted areas reached by random. They survive moderate desiccation and can live for four weeks in tap water. They show a tendency to migrate in all directions, not only upwards.
DISPERSAL AND FLIGHT RANGE OF SUBARCTIC MOSQUITOES MARKED WITH RADIOPHOSPHORUS
Authors: Jenkins Dale W. , Hassett Charles C.
Published: August 2008

The dispersal and flight range of the mosquito Aedes communis, a species characteristic of the northern coniferous forest, were studied at timberline at Churchill, Man., during the summer of 1950. Four million larvae were collected and reared in wooden tanks containing 0.05 μc. of P32 per larva. About 3,000,000 adults with an average radioactivity of 775 c.p.m. emerged and dispersed in the Warkworth area. One hundred and forty-one radioactive mosquitoes were recovered, of which 63 had dispersed from 150 ft. to 5000 ft., the average dispersal being 500 ft. The effective dispersal was determined to be about 0.25 miles. This study indicates that A. communis is a relatively sedentary mosquito and has a limited flight range in the northern coniferous forest in comparison with arctic tundra species. This mosquito rests in vegetation and does not attack human beings during the daytime. Additional data are presented on the habits of this and other northern species of mosquitoes.
DISEASES AND PARASITES OF THE MUSKRAT (ONDATRA ZIBETHICA) IN BRITISH COLUMBIA
Authors: Knight Iola Musfeldt
Published: August 2008

This investigation is based upon the examination of 205 muskrat carcasses taken at various times between October 1944 and May 1947 and derived from 17 different localities in British Columbia. Seventy-four per cent of these carcasses were parasitized by 13 species of internal parasites. These included: trematodes, Echinostomum coalitum, Echinoparyphium contiguum, Quinque-serialis quinqueserialis, Notocotylus urbanensis, and Plagiorchis proximus; cestodes, Hymenolepis evaginata and Hymenolepis octocoronata; nematodes, Capillaria ransomia, Trichuris opaca, and Hepaticola hepatica and a species of Acanthocephala, related to the genus Polymorphus (Family Corynosomidae). Two larval cestodes were found infecting the liver; the strobilocercus, Cysticercus fasciolaris (Taenia taeniaformis) and a proliferating cysticercus, Cladotaenia sp. Pathological lesions in the muskrats resulted from two different pulmonary infections, infections of wounds, and a type of tumor. It was found that: the muskrats in this province were not extensively parasitized; hence mortality due to excess parasitism is probably negligible. This paper includes a review of the parasites of the muskrat that have been recorded by other workers.
THE PROVENTRICULUS OF SOME LOCUSTS OF THE FAMILY EUMASTACIDAE (ORTHOPTERA) WITH REFERENCE TO ITS USE IN TAXONOMY
Authors: Judd W. W.
Published: August 2008

The structure of the proventriculus of four species of locusts in the family Eumastacidae is described, indicating that this family represents a line of descent distinct from other acridoid families in which the proventriculus has been studied.
STUDIES ON THE ENDOPARASITIC FAUNA OF TRINIDAD MAMMALS: VII. PARASITES OF HYSTRICOMORPH RODENTS
Authors: Cameron T. W. M. , Reesal M. R.
Published: August 2008

A possible new variety of cestode, Raillietina (R.) demerariensis var. trinitatae, and two new varieties, Trichuris gracilis var. trinitatae and Aspidodera binansata var. agoutiae and a new species of nematode, Helminthoxys urichi are recorded from the agouti and lappe from Trinidad, B.W.I.
APHID INFESTATIONS ON KATAHDIN AND ON A SEEDLING RESISTANT TO MYZUS PERSICAE (SULZ.), WITH TWO DATES OF PLANTING
Authors: Bradley R. H. E. , Ganong R. Y.
Published: August 2008

In August under field conditions, on early planted plots, the number of Myzus persicae per plant was usually over five times as great on Katahdin as on B294-85; and the number of Aphis abbreviata was over 10 times as great on Katahdin as on B294-85. The differences in the aphid populations on the late planted plots of Katahdin and of B294-85 were similar, but not so great. There were no consistent differences in the numbers of Macrosiphum solanifolii on Katahdin and on B294-85. During August, the rates of increase of each species were similar for both varieties and dates of planting. The number of aphids per plant was many times greater on the early planted than on the late planted plots, the differences being greater between the Katahdin than between the B294-85 plantings. When the populations were expressed as aphids per unit leaf area, the distribution of each species on the top, middle, and bottom leaves was similar in all cases.
THE RELATIONSHIP OF THE SPRUCE BUDWORM (CHORISTONEURA FUMIFERANA, CLEM.) TO THE FLOWERING CONDITION OF BALSAM FIR (ABIES BALSAMEA (L.) MILL.)
Authors: Blais J. R.
Published: August 2008

Populations of the spruce budworm were studied on flowering and nonflowering balsam fir trees. Generally more eggs were found on the flowering trees. The flowering balsam fir trees were found to harbor higher populations in the early larval stages owing to the presence on these trees of staminate flowers and flower cups. The behavior of the larvae in relation to staminate flowers and flower cups was studied in both the field and the laboratory. Larvae that fed partially on pollen developed more rapidly than larvae that fed exclusively on foliage. Pollen as a food did not appear to have any direct effect on survival or fecundity. Other experiments showed that mortality was higher, development retarded, and fecundity reduced in insects forced to feed on old foliage in contrast with those fed on the current year's growth. Defoliation was more severe on flowering trees in the earlier stages of the infestation. However, as populations increased, wandering increased owing to competition for food. This resulted in an overflow of larvae from flowering to nonflowering trees.
EFFECTS OF TEMPERATURE AND WORK ON METABOLISM, BODY TEMPERATURE, AND INSULATION: RESULTS WITH MICE
Authors: Hart J. S.
Published: August 2008

For inactive mice, metabolism below the critical temperature was proportional to the thermal gradient, and body temperature and insulation were constant in animals acclimated to 6 °C., but not in those acclimated to 20 °C. For active mice, the same work caused the same increase in metabolism at all temperatures, but metabolism during work was not proportional to the thermal gradient. During work, with decreasing temperature, body temperature was relatively stable in 6 °C. mice but fell appreciably in 20 °C. mice. Over-all insulation was lower in working than in inactive animals, but in the 6 °C. acclimated mice there was a substantial improvement in insulation during work as the temperature decreased. Reports on other animals and humans also suggest that work may lower insulation. When work decreases insulation, much of the heat produced by the work, unlike that produced by SDA, may not be available for maintaining body temperature in a cold environment.
IN WHAT EMBRYONIC STAGE DO THE EGGS OF NEODIPRION ENTER THE WINTER DIAPAUSE?
Authors: Brygider Wolodymyr
Published: August 2008

This paper deals with the early embryonic development of Neodiprion banksianae Roh., N. nanulus Schedl., and N. sertifer Geoff., up to the initiation of winter diapause. Methods of preparation are described and the course of development is traced and described with the aid of two text-figures and two plates. The three species were found to enter diapause at approximately the same stage, but some differences in the details of their embryonic structure were discovered.
MOVEMENT OF MATERIALS IN THE HYPOLIMNION OF A LAKE AS STUDIED BY THE ADDITION OF RADIOACTIVE PHOSPHORUS
Authors: McCarter J. A. , Hayes F. R. , Jodrey L. H. , Cameron M. L.
Published: August 2008

Approximately 100 millicuries of radioactive phosphorus in the form of potassium dihydrogen phosphate were introduced into the hypolimnion of a small acid-bog lake by causing a bottle containing a solution of the material to burst about 3 meters below the thermocline and about 1 meter above the bottom. The depth of water at the point of introduction of the bottle was 6 meters. After bursting the bottle the distribution of the radioactive phosphate through the waters of the lake was followed by withdrawing and analyzing samples of water from different localities and from different depths. Samples of ooze from the bottom of the lake were also taken for measurement of their content of radioactive phosphorus. It was found that the radioactive phosphate moved through the hypolimnion in a lateral direction at a rate of some 3 meters per day. Although it moved laterally to the end of the lake (42 meters), the extent of its movement vertically appeared to be not greater than 2 or 3 meters, i.e., it scarcely penetrated the thermocline to a measurable extent. The radioactive phosphorus appeared early in the mud of the lake bottom, and its concentration there increased to such values as to suggest that a large part was removed by the mud, probably by a process of exchange of phosphate between mud and water.
SOME EFFECTS OF TEMPERATURE ON DEVELOPMENT AND DIAPAUSE IN EGGS OF MELANOPLUS BIVITTATUS (SAY) (ORTHOPTERA: ACRIDIDAE)
Authors: Church N. S. , Salt R. W.
Published: August 2008

The normal hatching curve of postdiapause eggs of Melanoplus bivittatus (Say) at 25 °C. is described and compared with those at 10, 15, and 20 °C. The rate of postdiapause katatrepsic development was proportional to temperature; extrapolation showed 12 °C. to be the theoretical threshold of normal development for this stage. However, restricted postdiapause development or conditioning occurred at 5 °C. At 10 °C, and less extensively at 5 and 15 °C., partial development took place, resulting in deformed embryos.Diapause, which is most readily broken at 5 °C., may persist for more than 100 days at that temperature. It can also be eliminated at 25 °C., but much more slowly. Alternating-temperature experiments disclosed no marked differences in the ease of diapause-breaking at various embryonic ages. The suggestion is made that temperature alternations hinder diapause-breaking and morphogenesis.The threshold of development concept is briefly discussed with regard to some of the observations reported.
THE AEROBIC BACTERIA ASSOCIATED WITH THE EASTERN HEMLOCK LOOPER LAMBDINA FISCELLARIA (GN.)
Authors: Angus T. A.
Published: August 2008

A study was made of healthy hemlock loopers (Lambdina fiscellaria Gn.) to determine whether a specific bacterial flora is associated with this insect. Larvae, pupae, adults, and eggs were examined by a number of methods and the bacteria found were cultured and classified. Organisms belonging to nine genera of bacteria were isolated and they were principally of foliage-contaminating or soil types that could be ingested with the insects' food. Few of the ingested bacteria survive the digestive process. It is concluded that the bacterial flora is adventitious.