bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequencing and Diversity Analyses Reveal Extensive Similarities between Some Epsilon-Toxin-Encoding Plasmids and the pCPF5603Clostridium perfringensEnterotoxin Plasmid
Authors: Miyamoto Kazuaki , Li Jihong , Sayeed Sameera , Akimoto Shigeru , McClane Bruce A. 
Published: September 2008

ABSTRACTClostridium perfringenstype B and D isolates produce epsilon-toxin, the third most potent clostridial toxin. The epsilon-toxin gene (etx) is plasmid borne in type D isolates, butetxgenetics have been poorly studied in type B isolates. This study reports the first sequencing of anyetxplasmid, i.e., pCP8533etx, from type B strain NCTC8533. Thisetxplasmid is 64.7 kb, carriestcpconjugative transfer genes, and encodes additional potential virulence factors including beta2-toxin, sortase, and collagen adhesin but not beta-toxin. Interestingly, nearly 80% of pCP8533etx open reading frames (ORFs) are also present on pCPF5603, an enterotoxin-encoding plasmid from type A isolate F5603. Pulsed-field gel electrophoresis and overlapping PCR indicated that a pCP8533etx-likeetxplasmid is also present in most, if not all, other type B isolates and some beta2-toxin-positive,cpe-negative type D isolates, while other type D isolates carry differentetxplasmids. Sequences upstream of theetxgene vary between type B isolates and some type D isolates that do not carry a pCP8533etx-likeetxplasmid. However, nearly all type B and D isolates have anetxlocus with an upstream IS1151, and thoseetxloci typically reside near adcmORF. These results suggest that pCPF5603 and pCP8533etx evolved from insertion of mobile genetic elements carrying enterotoxin oretxgenes, respectively, onto a common progenitor plasmid.
Ethanolamine Activates a Sensor Histidine Kinase Regulating Its Utilization in
Enterococcus faecalis
Authors: Del Papa María Florencia , Perego Marta 
Published: September 2008

ABSTRACT

Enterococcus faecalis
is a gram-positive commensal bacterium of the human intestinal tract. Its opportunistic pathogenicity has been enhanced by the acquisition of multiple antibiotic resistances, making the treatment of enterococcal infections an increasingly difficult problem. The extraordinary capacity of this organism to colonize and survive in a wide variety of ecological niches is attributable, at least in part, to signal transduction pathways mediated by two-component systems (TCS). Here, the ability of
E. faecalis
to utilize ethanolamine as the sole carbon source is shown to be dependent upon the RR-HK17 (EF1633-EF1632) TCS. Ethanolamine is an abundant compound in the human intestine, and thus, the ability of bacteria to utilize it as a source of carbon and nitrogen may provide an advantage for survival and colonization. Growth of
E. faecalis
in a synthetic medium with ethanolamine was abolished in the response regulator RR17 mutant strain. Transcription of the response regulator gene was induced by the presence of ethanolamine. Ethanolamine induced a 15-fold increase in the rate of autophosphorylation in vitro of the HK17 sensor histidine kinase, indicating that this is the ligand recognized by the sensor domain of the kinase. These results assign a role to the RR-HK17 TCS as coordinator of the enterococcal response to specific nutritional conditions existing at the site of bacterial invasion, the intestinal tract of an animal host.
PilF Is an Outer Membrane Lipoprotein Required for Multimerization and Localization of thePseudomonas aeruginosaType IV Pilus Secretin
Authors: Koo Jason , Tammam Stephanie , Ku Shao-Yang , Sampaleanu Liliana M. , Burrows Lori L. , Howell P. Lynne 
Published: September 2008

ABSTRACTType IV pili (T4P) are retractile appendages that contribute to the virulence of bacterial pathogens. PilF is aPseudomonas aeruginosalipoprotein that is essential for T4P biogenesis. Phenotypic characterization of apilFmutant confirmed that T4P-mediated functions are abrogated: T4P were no longer present on the cell surface, twitching motility was abolished, and the mutant was resistant to infection by T4P retraction-dependent bacteriophage. The results of cellular fractionation studies indicated that PilF is the outer membrane pilotin required for the localization and multimerization of the secretin, PilQ. Mutation of the putative PilF lipidation site untethered the protein from the outer membrane, causing secretin assembly in both inner and outer membranes. T4P-mediated twitching motility and bacteriophage susceptibility were moderately decreased in the lipidation site mutant, while cell surface piliation was substantially reduced. The tethering of PilF to the outer membrane promotes the correct localization of PilQ and appears to be required for the formation of stable T4P. Our 2.0-Å structure of PilF revealed a superhelical arrangement of six tetratricopeptide protein-protein interaction motifs that may mediate the contacts with PilQ during secretin assembly. An alignment of pseudomonad PilF sequences revealed three highly conserved surfaces that may be involved in PilF function.
Identification of Genes Encoding the Folate- and Thiamine-Binding Membrane Proteins in Firmicutes
Authors: Eudes Aymerick , Erkens Guus B. , Slotboom Dirk J. , Rodionov Dmitry A. , Naponelli Valeria , Hanson Andrew D. 
Published: September 2008

ABSTRACT

Genes encoding high-affinity folate- and thiamine-binding proteins (FolT, ThiT) were identified in the
Lactobacillus casei
genome, expressed in
Lactococcus lactis
, and functionally characterized. Similar genes occur in many Firmicutes, sometimes next to folate or thiamine salvage genes. Most
thiT
genes are preceded by a thiamine riboswitch.
The Human Immunodeficiency Virus Type 1 Envelope Confers Higher Rates of Replicative Fitness to Perinatally Transmitted Viruses than to Nontransmitted Viruses
Authors: Kong Xiaohong , West John T. , Zhang Hong , Shea Danielle M. , M'soka Tendai J. , Wood Charles 
Published: September 2008

ABSTRACT

Selection of a minor viral genotype during perinatal transmission of human Immunodeficiency virus type 1 (HIV-1) has been observed, but there is a lack of information on the correlation of the restrictive transmission with biological properties of the virus, such as replicative fitness. Recombinant viruses expressing the enhanced green fluorescent protein or the
Discosoma
sp. red fluorescent (DsRed2) protein carrying the V1 to V5 regions of
env
from seven mother-infant pairs (MIPs) infected by subtype C HIV-1 were constructed, and competition assays were carried out to compare the fitness between the transmitted and nontransmitted viruses. Flow cytometry was used to quantify the frequency of infected cells, and the replicative fitness was determined based on a calculation that takes into account replication of competing viruses in a single infection versus dual infections. Transmitted viruses from five MIPs with the mothers chronically infected showed a restrictive
env
genotype, and all the recombinant viruses carrying the infants' Env had higher replicative fitness than those carrying the Env from the mothers. This growth fitness is lineage specific and can be observed only within the same MIP. In contrast, in two MIPs where the mothers had undergone recent acute infection, the viral Env sequences were similar between the mothers and infants and showed no further restriction in quasispecies during perinatal transmission. The recombinant viruses carrying the Env from the infants' viruses also showed replication fitness similar to those carrying the mothers' Env proteins. Our results suggest that newly transmitted viruses from chronically infected mothers have been selected to have higher replicative fitness to favor transmission, and this advantage is conferred by the V1 to V5 region of Env of the transmitted viruses. This finding has important implications for vaccine design or development of strategies to prevent HIV-1 transmission.
Entry from the Cell Surface of Severe Acute Respiratory Syndrome Coronavirus with Cleaved S Protein as Revealed by Pseudotype Virus Bearing Cleaved S Protein
Authors: Watanabe Rie , Matsuyama Shutoku , Shirato Kazuya , Maejima Masami , Fukushi Shuetsu , Morikawa Shigeru , Taguchi Fumihiro 
Published: September 2008

ABSTRACT
Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is known to take an endosomal pathway for cell entry; however, it is thought to enter directly from the cell surface when a receptor-bound virion spike (S) protein is affected by trypsin, which induces cleavage of the S protein and activates its fusion potential. This suggests that SARS-CoV bearing a cleaved form of the S protein can enter cells directly from the cell surface without trypsin treatment. To explore this possibility, we introduced a furin-like cleavage sequence in the S protein at amino acids 798 to 801 and found that the mutated S protein was cleaved and induced cell fusion without trypsin treatment when expressed on the cell surface. Furthermore, a pseudotype virus bearing a cleaved S protein was revealed to infect cells in the presence of a lysosomotropic agent as well as a protease inhibitor, both of which are known to block SARS-CoV infection via an endosome, whereas the infection of pseudotypes with an uncleaved, wild-type S protein was blocked by these agents. A heptad repeat peptide, derived from a SARS-CoV S protein that is known to efficiently block infections from the cell surface, blocked the infection by a pseudotype with a cleaved S protein but not that with an uncleaved S protein. Those results indicate that SARS-CoV with a cleaved S protein is able to enter cells directly from the cell surface and agree with the previous observation of the protease-mediated cell surface entry of SARS-CoV.
Multiple Virus Lineages Sharing Recent Common Ancestry Were Associated with a Large Rift Valley Fever Outbreak among Livestock in Kenya during 2006-2007
Authors: Bird Brian H. , Githinji Jane W. K. , Macharia Joseph M. , Kasiiti Jacqueline L. , Muriithi Rees M. , Gacheru Stephen G. , Musaa Joseph O. , Towner Jonathan S. , Reeder Serena A. , Oliver Jennifer B. , Stevens Thomas L. , Erickson Bobbie R. , Morgan Laura T. , Khristova Marina L. , Hartman Amy L. , Comer James A. , Rollin Pierre E. , Ksiazek Thomas G. , Nichol Stuart T. 
Published: September 2008

ABSTRACT
Rift Valley fever (RVF) virus historically has caused widespread and extensive outbreaks of severe human and livestock disease throughout Africa, Madagascar, and the Arabian Peninsula. Following unusually heavy rainfall during the late autumn of 2006, reports of human and animal illness consistent with RVF virus infection emerged across semiarid regions of the Garissa District of northeastern Kenya and southern Somalia. Following initial RVF virus laboratory confirmation, a high-throughput RVF diagnostic facility was established at the Kenyan Central Veterinary Laboratories in Kabete, Kenya, to support the real-time identification of infected livestock and to facilitate outbreak response and control activities. A total of 3,250 specimens from a variety of animal species, including domesticated livestock (cattle, sheep, goats, and camels) and wildlife collected from a total of 55 of 71 Kenyan administrative districts, were tested by molecular and serologic assays. Evidence of RVF infection was found in 9.2% of animals tested and across 23 districts of Kenya, reflecting the large number of affected livestock and the geographic extent of the outbreak. The complete S, M, and/or L genome segment sequence was obtained from a total of 31 RVF virus specimens spanning the entire known outbreak period (December-May) and geographic areas affected by RVF virus activity. Extensive genomic analyses demonstrated the concurrent circulation of multiple virus lineages, gene segment reassortment, and the common ancestry of the 2006/2007 outbreak viruses with those from the 1997-1998 east African RVF outbreak. Evidence of recent increases in genomic diversity and effective population size 2 to 4 years prior to the 2006-2007 outbreak also was found, indicating ongoing RVF virus activity and evolution during the interepizootic/epidemic period. These findings have implications for further studies of basic RVF virus ecology and the design of future surveillance/diagnostic activities, and they highlight the critical need for safe and effective vaccines and antiviral compounds to combat this significant veterinary and public health threat.
Source mechanisms of vulcanian eruptions at Mt. Asama, Japan, inferred from volcano seismic signals
Authors: Ohminato Takao 
Published: September 2008

Abstract

During the 2004 Asama volcanic activity, five summit eruptions, accompanied by the broadband seismic signals, were observed. We re-analyse the broadband waveform data analysed by

Ohminato
et al.
(2006)

using relaxed restrictions. The results are essentially the same as those shown in the previous study. The results of the waveform inversions that assume a point source show that the force system is dominated by vertical single-force components. The source depths with dominant single-force components are 200–300 m beneath the summit crater. In the source-time history of the vertical single-force component, two downward forces separated by an upward force lasting for 5–6 s are clearly seen. We conduct a grid search for the best combination of two point sources, each consisting of a single-force component. The best waveform-match solution was obtained when one of them is positioned near the top of the conduit, and the other source is positioned 2000 m below the upper source. When a combination of single-force and moment-tensor components is assumed for the two-point source model, the moment source is located out of the vertical hypocentre distribution, suggesting a steeply inclined conduit.
The feasibility of generating low-frequency volcano seismicity by flow through a deformable channel
Authors: Rust A. C. , Balmforth N. J. , Mandre S. 
Published: September 2008

Abstract

Oscillations generated by flow of magmatic or hydrothermal fluids through tabular channels in elastic rocks are a possible source of low-frequency seismicity. We assess the conditions required to generate oscillations of approximately 1 Hz
via
hydrodynamic flow instabilities (roll waves), flow-destabilized standing waves set up on the elastic channel walls (wall modes), and unstable normal modes ringing in an adjacent fluid reservoir (clarinet modes). Stability criteria are based on physical and dimensional arguments, and discussion of destabilized elastic modes is supplemented with laboratory experiments of gas flow through a channel in a block of gelatine, and between a rigid plate and a rubber membrane. For each of the mechanisms considered, oscillations are generated if flow speeds exceed a critical value. Roll waves are waves of channel thickness variation that propagate in the direction of flow and are equivalent to traveling crack waves. The convective instability criterion is that the flow is faster than those travelling waves. Similarly, wall modes and clarinet modes require that the flow speed exceeds a critical value related to a wave speed (e.g. elastic or acoustic wave) multiplied by a geometrical factor. Flow destabilized modes offer a plausible explanation for low-frequency volcano seismicity, but there are limitations on what kind of standing waves comprises them.
Shallow-conduit dynamics at Stromboli Volcano, Italy, imaged from waveform inversions
Authors: Chouet Bernard , Dawson Phillip , Martini Marcello 
Published: September 2008

Abstract
Modelling of Very-Long-Period (VLP) seismic data recorded during explosive activity at Stromboli in 1997 provides an image of the uppermost 1 km of its volcanic plumbing system. Two distinct dyke-like conduit structures are identified, each representative of explosive eruptions from two different vents located near the northern and southern perimeters of the summit crater. Observed volumetric changes in the dykes are viewed as the result of a piston-like action of the magma associated with the disruption of a gas slug transiting through discontinuities in the dyke apertures. Accompanying these volumetric source components are single vertical forces resulting from an exchange of linear momentum between the source and the Earth. In the dyke system underlying the northern vent, a primary disruption site is observed at an elevation near 440 m where a bifurcation in the conduit occurs. At a depth of 80 m below sea level, a sharp corner in the conduit marks another location where the elastic response of the solid to the action of the upper source induces pressure and momentum changes in the magma. In the conduit underlying the southern vent, the junction of two inclined dykes with a sub-vertical dyke at 520 m elevation is a primary site of gas slug disruption, and another conduit corner 280 m below sea level represents a coupling location between the elastic response of the solid and fluid motion.
From sound waves to bubbling within a magma reservoir: comparison between eruptions at Etna (2001, Italy) and Kilauea (Hawaii)
Authors: Vergniolle S. 
Published: September 2008

Abstract

The 2001 eruption of Etna, prior to the flank eruption, has shown an alternation between episodes rich in gas, composed with a series of Strombolian explosions sometimes leading to a fire fountain, and repose periods. The regular alternation results from the coalescence of a foam trapped in the reservoir and periodically rebuilt prior to each episode. The degassing of a magma reservoir depends on bubble diameter, gas volume fraction, surface area and height of the reservoir. These four parameters are deduced from the measured gas flux, the timescale over which the gas flux decreases and the foam dynamics. The dimensionless foam thickness, 0.76 for a purely Strombolian episode, increases to 0.89 for an episode leading to a fire fountain, indicating a more efficient foam coalescence. At Etna, the bubble diameter, gas volume fraction, surface area and height of the reservoir are estimated at 0.50–0.59 mm, 0.25–0.39%, >0.20 km
2
and 97–220 m, respectively. At Kilauea, the excellent agreement between the prediction of the foam model, 0.94–1.2 km
2
and that resulting from deformations, 1 km
2
, reinforces the validity of the foam model qualitatively and quantitatively. The thickness of the degassing reservoir, 16–12 m in 1959, is now 1.3–1.1 km.
Antixenograft tumor activity of a humanized anti-insulin-like growth factor-I receptor monoclonal antibody is associated with decreased AKT activation and glucose uptake
Authors: Shang Yonglei , Mao Yifan , Batson Jennifer , Scales Suzie J. , Phillips Gail , Lackner Mark R. , Totpal Klara , Williams Simon , Yang Jihong , Tang Zhijun , Modrusan Zora , Tan Christine , Liang Wei-Ching , Tsai Siao Ping , Vanderbilt Alexander , Kozuka Kenji , Hoeflich Klaus , Tien Janet , Ross Sarajane , Li Congfen , Lee Sang Hoon , Song An , Wu Yan , Stephan Jean-Philippe , Ashkenazi Avi , Zha Jiping 
Published: September 2008

Abstract
The insulin-like growth factor (IGF) system consists of two ligands (IGF-I and IGF-II), which both signal through IGF-I receptor (IGF-IR) to stimulate proliferation and inhibit apoptosis, with activity contributing to malignant growth of many types of human cancers. We have developed a humanized, affinity-matured anti-human IGF-IR monoclonal antibody (h10H5), which binds with high affinity and specificity to the extracellular domain. h10H5 inhibits IGF-IR-mediated signaling by blocking IGF-I and IGF-II binding and by inducing cell surface receptor down-regulation via internalization and degradation, with the extracellular and intracellular domains of IGF-IR being differentially affected by the proteasomal and lysosomal inhibitors. In vitro, h10H5 exhibits antiproliferative effects on cancer cell lines. In vivo, h10H5 shows single-agent antitumor efficacy in human SK-N-AS neuroblastoma and SW527 breast cancer xenograft models and even greater efficacy in combination with the chemotherapeutic agent docetaxel or an anti–vascular endothelial growth factor antibody. Antitumor activity of h10H5 is associated with decreased AKT activation and glucose uptake and a 316-gene transcription profile with significant changes involving DNA metabolic and cell cycle machineries. These data support the clinical testing of h10H5 as a biotherapeutic for IGF-IR-dependent human tumors and furthermore illustrate a new method of monitoring its activity noninvasively in vivo via 2-fluoro-2-deoxy-d-glucose-positron emission tomography imaging. [Mol Cancer Ther 2008;7(9):2599–608]
Antileukemia effects of xanthohumol in Bcr/Abl-transformed cells involve nuclear factor-κB and p53 modulation
Authors: Monteghirfo Stefano , Tosetti Francesca , Ambrosini Claudia , Stigliani Sara , Pozzi Sarah , Frassoni Francesco , Fassina Gianfranco , Soverini Simona , Albini Adriana , Ferrari Nicoletta 
Published: September 2008

Abstract
The oncogenic Bcr-Abl tyrosine kinase activates various signaling pathways including phosphoinositide 3-kinase/Akt and nuclear factor-κB that mediate proliferation, transformation, and apoptosis resistance in Bcr-Abl(+) myeloid leukemia cells. The hop flavonoid xanthohumol inhibits tumor growth by targeting the nuclear factor-κB and Akt pathways and angiogenesis. Here, we show that xanthohumol has in vitro activity against Bcr-Abl(+) cells and clinical samples and retained its cytotoxicity when imatinib mesylate–resistant K562 cells were examined. Xanthohumol inhibition of K562 cell viability was associated with induction of apoptosis, increased p21 and p53 expression, and decreased survivin levels. We show that xanthohumol strongly inhibited Bcr-Abl expression at both mRNA and protein levels and show that xanthohumol caused elevation of intracellular reactive oxygen species and that the antioxidant N-acetylcysteine blunted xanthohumol-induced events. Further, we observed that xanthohumol inhibits leukemia cell invasion, metalloprotease production, and adhesion to endothelial cells, potentially preventing in vivo life-threatening complications of leukostasis and tissue infiltration by leukemic cells. As structural mutations and/or gene amplification in Bcr-Abl can circumvent an otherwise potent anticancer drug such as imatinib, targeting Bcr-Abl expression as well as its kinase activity could be a novel additional therapeutic approach for the treatment of Bcr-Abl(+) myeloid leukemia. [Mol Cancer Ther 2008;7(9):2692–702]
SPC3042: a proapoptotic survivin inhibitor
Authors: Hansen Jens Bo , Fisker Niels , Westergaard Majken , Kjærulff Lene Sønderby , Hansen Henrik Frydenlund , Thrue Charlotte Albaek , Rosenbohm Christoph , Wissenbach Margit , Ørum Henrik , Koch Troels 
Published: September 2008

Abstract
The ability to regulate the cellular homeostasis of a higher organism through tight control of apoptosis and cell division is crucial for life. Dysregulation of these mechanisms is often associated with cancerous phenotypes in cells. Optimal cancer therapy is a fine balance between effective cancer cell killing and at the same time minimizing, or avoiding, damage to the surrounding healthy tissue. To obtain this, it is necessary to identify and inhibit molecular targets on which the cancer cells are strongly dependent. Survivin represents such a target, and it has been published previously that peptide vaccines, the small-molecule YM155, and the antisense molecule LY2181308/ISIS23722, via different mechanisms, have been used as survivin inhibitors. In this article, a new potent antisense inhibitor of survivin, SPC3042, is presented, and the properties of SPC3042 are compared with the previously published antisense drug, LY2181308/ISIS23722. SPC3042 is a 16-mer locked nucleic acid (LNA) oligonucleotide and designed as a fully phosphorothiolated gapmer containing 7 LNA nucleotides in the flanks. The LNA nucleotides in SPC3042 provide nuclease stability and higher potency for survivin mRNA inhibition compared with earlier generations of antisense reagents. It is shown that the down-regulation of survivin with SPC3042 leads to cell cycle arrest, pronounced cellular apoptosis, and down-regulation of Bcl-2. It is also shown that SPC3042 is a sensitizer of prostate cancer cells to Taxol treatment in vitro and in vivo. [Mol Cancer Ther 2008;7(9):2736–45]