bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomewide Expression Profiling of Cryptolepine-Induced Toxicity inSaccharomyces cerevisiae
Authors: Rojas Marta , Wright Colin W. , Piña Benjamin , Portugal José 
Published: August 2008

ABSTRACTWe 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

ABSTRACT

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

ABSTRACTIn 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

ABSTRACT

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

ABSTRACT

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

ABSTRACTThe 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

ABSTRACTInfection 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

ABSTRACT

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

ABSTRACT

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

ABSTRACT

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.
A policy-aware switching layer for data centers
Authors: Joseph Dilip A. , Tavakoli Arsalan , Stoica Ion 
Published: August 2008

Data centers deploy a variety of middleboxes (e.g., firewalls, load balancers and SSL offloaders) to protect, manage and improve the performance of applications and services they run. Since existing networks provide limited support for middleboxes, administrators typically overload path selection mechanisms to coerce traffic through the desired sequences of middleboxes placed on the network path. These ad-hoc practices result in a data center network that is hard to configure and maintain, wastes middlebox resources, and cannot guarantee middlebox traversal under network churn.
To address these issues, we propose the policy-aware switching layer or PLayer, a new layer-2 for data centers consisting of inter-connected policy-aware switches or pswitches. Unmodified middleboxes are placed off the network path by plugging them into pswitches. Based on policies specified by administrators, pswitches explicitly forward different types of traffic through different sequences of middleboxes. Experiments using our prototype software pswitches suggest that the PLayer is flexible, uses middleboxes efficiently, and guarantees correct middlebox traversal under churn.
A scalable, commodity data center network architecture
Authors: Al-Fares Mohammad , Loukissas Alexander , Vahdat Amin 
Published: August 2008

Today's data centers may contain tens of thousands of computers with significant aggregate bandwidth requirements. The network architecture typically consists of a tree of routing and switching elements with progressively more specialized and expensive equipment moving up the network hierarchy. Unfortunately, even when deploying the highest-end IP switches/routers, resulting topologies may only support 50% of the aggregate bandwidth available at the edge of the network, while still incurring tremendous cost. Non-uniform bandwidth among data center nodes complicates application design and limits overall system performance.In this paper, we show how to leverage largely commodity Ethernet switches to support the full aggregate bandwidth of clusters consisting of tens of thousands of elements. Similar to how clusters of commodity computers have largely replaced more specialized SMPs and MPPs, we argue that appropriately architected and interconnected commodity switches may deliver more performance at less cost than available from today's higher-end solutions. Our approach requires no modifications to the end host network interface, operating system, or applications; critically, it is fully backward compatible with Ethernet, IP, and TCP.
Learning to share
Authors: Rahul Hariharan , Kushman Nate , Katabi Dina , Sodini Charles , Edalat Farinaz 
Published: August 2008

Wideband technologies in the unlicensed spectrum can satisfy the ever-increasing demands for wireless bandwidth created by emerging rich media applications. The key challenge for such systems, however, is to allow narrowband technologies that share these bands (say, 802.11 a/b/g/n, Zigbee) to achieve their normal performance, without compromising the throughput or range of the wideband network.
This paper presents SWIFT, the first system where high-throughput wideband nodes are shown in a working deployment to coexist with unknown narrowband devices, while forming a network of their own. Prior work avoids narrowband devices by operating below the noise level and limiting itself to a single contiguous unused band. While this achieves coexistence, it sacrifices the throughput and operating distance of the wideband device. In contrast, SWIFT creates high throughput wireless links by weaving together non-contiguous unused frequency bands that change as narrowband devices enter or leave the environment. This design principle of cognitive aggregation allows SWIFT to achieve coexistence, while operating at normal power, and thereby obtaining higher throughput and greater operating range. We implement SWIFT on a wideband hardware platform, and evaluate it in the presence of 802.11 devices. In comparison to a baseline that coexists with narrowband devices by operating below their noise level, SWIFT is equally narrowband-friendly but achieves 3.6-10.5x higher throughput and 6x greater range.