bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Proportion of Fluoroquinolone-Resistant Mycobacterium tuberculosis Isolates with Novel Gyrase Polymorphisms and a
gyrA
Region Associated with Fluoroquinolone Susceptibility
Authors: Devasia Rose , Blackman Amondrea , Eden Svetlana , Li Haijing , Maruri Fernanda , Shintani Ayumi , Alexander Charles , Kaiga Anne , Stratton Charles W. , Warkentin Jon , Tang Yi-Wei , Sterling Timothy R. 
Published: December 2011

ABSTRACT

Fluoroquinolone resistance in
Mycobacterium tuberculosis
can be conferred by mutations in
gyrA
or
gyrB
. The prevalence of resistance mutations outside the quinolone resistance-determining region (QRDR) of
gyrA
or
gyrB
is unclear, since such regions are rarely sequenced.
M. tuberculosis
isolates from 1,111 patients with newly diagnosed culture-confirmed tuberculosis diagnosed in Tennessee from 2002 to 2009 were screened for phenotypic ofloxacin resistance (>2 μg/ml). For each resistant isolate, two ofloxacin-susceptible isolates were selected: one with antecedent fluoroquinolone exposure and one without. The complete
gyrA
and
gyrB
genes were sequenced and compared with
M. tuberculosis
H37Rv. Of 25 ofloxacin-resistant isolates, 11 (44%) did not have previously reported resistance mutations. Of these, 10 had novel polymorphisms: 3 in the QRDR of
gyrA
, 1 in the QRDR of
gyrB
, and 6 outside the QRDR of
gyrA
or
gyrB
; 1 did not have any gyrase polymorphisms. Polymorphisms in
gyrA
codons 1 to 73 were more common in fluoroquinolone-susceptible than in fluoroquinolone-resistant strains (20% versus 0%;
P
= 0.016). In summary, almost half of fluoroquinolone-resistant
M. tuberculosis
isolates did not have previously described resistance mutations, which has implications for genotypic diagnostic tests.
First Isolation of Cryptococcus uzbekistanensis from an Immunocompromised Patient with Lymphoma
Authors: Powel Michael S. , Alizadeh Ash A. , Budvytiene Indre , Schaenman Joanna M. , Banaei Niaz 
Published: December 2011

ABSTRACT

Cryptococcus
species are known agents of opportunistic infections in healthy and immunocompromised hosts. Here we describe the first case of
Cryptococcus uzbekistanensis
causing bone marrow infection in an elderly Asian man with undiagnosed T cell lymphoma presenting with fever of unknown origin, pancytopenia, and exposure to chicken manure.
Genetic Features Differentiating Bovine, Food, and Human Isolates of Shiga Toxin-Producing Escherichia coli O157 in The Netherlands
Authors: Franz Eelco , van Hoek Angela H. A. M. , van der Wal Fimme J. , de Boer Albert , Zwartkruis-Nahuis Ans , van der Zwaluw Kim , Aarts Henk J. M. , Heuvelink Annet E. 
Published: December 2011

ABSTRACT

The frequency of
Escherichia coli
O157 genotypes among bovine, food, and human clinical isolates from The Netherlands was studied. Genotyping included the lineage-specific polymorphism assay (LSPA6), the Shiga-toxin-encoding bacteriophage insertion site assay (SBI), and PCR detection and/or subtyping of virulence factors and markers [
stx1
,
stx
2a
/
stx
2c
,
q21
/
Q933
,
tir
(
A255T
), and
rhsA
(
C3468G
)]. LSPA6 lineage II dominated among bovine isolates (63%), followed by lineage I/II (35.6%) and lineage I (1.4%). In contrast, the majority of the human isolates were typed as lineage I/II (77.6%), followed by lineage I (14.1%) and lineage II (8.2%). Multivariate analysis revealed that the
tir
(
A255T
) SNP and the

stx
2a
/stx

2c
gene variants were the genetic features most differentiating human from bovine isolates. Bovine and food isolates were dominated by
stx
2c
(86.4% and 65.5%, respectively). Among human isolates, the frequency of
stx
2c
was 36.5%, while the frequencies of
stx
2a
and
stx
2a
plus
stx
2c
were 41.2% and 22.4%, respectively. Bovine isolates showed equal distribution of
tir
(255A) (54.8%) and
tir
(255T) (45.2%), while human isolates were dominated by the
tir
(255T) genotype (92.9%). LSPA6 lineage I isolates were all genotype
stx
2c
and
tir
(255T), while LSPA6 lineage II was dominated by
tir
(255A) (86.4%) and
stx
2c
(90.9%). LSPA6 lineage I/II isolates were all genotype
tir
(255T) but showed more variation in
stx
2
types. The results support the hypothesis that in The Netherlands, the genotypes primarily associated with human disease form a minor subpopulation in the bovine reservoir. Comparison with published data revealed that the distribution of LSPA6 lineages among bovine and human clinical isolates differs considerably between The Netherlands and North America.
Molecular Evidence for Zoonotic Transmission of an Emergent, Highly Pathogenic Campylobacter jejuni Clone in the United States
Authors: Sahin Orhan , Fitzgerald Collette , Stroika Steven , Zhao Shaohua , Sippy Rachel J. , Kwan Patrick , Plummer Paul J. , Han Jing , Yaeger Michael J. , Zhang Qijing 
Published: December 2011

ABSTRACTCampylobacter jejuniis a major zoonotic pathogen. A highly virulent, tetracycline-resistantC. jejuniclone (clone SA) has recently emerged in ruminant reservoirs and has become the predominant cause of sheep abortion in the United States. To determine whether clone SA is associated with human disease, we compared the clinical isolates of clone SA from sheep abortions with the human isolates of the PulseNet NationalCampylobacterdatabases at the CDC and the FDA using pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and serotyping. The combined SmaI and KpnI PFGE pattern designations of clone SA from sheep were indistinguishable from those of 123 (9.03%) humanC. jejuniisolates (total, 1,361) in the CDC database, among which 56 were associated with sporadic infections and 67 were associated with outbreaks that occurred in multiple states from 2003 to 2010. Most of the outbreaks were attributed to raw milk, while the sources for most of the sporadic cases were unknown. All clone SA isolates examined, including PFGE-matched human isolates, belong to sequence type 8 (ST-8) by MLST and serotype HS:1,8, further indicating the clonality of the related isolates from different host species. Additionally,C. jejuniclone SA was identified in raw milk, cattle feces, the feces and bile of healthy sheep, and abortion cases of cattle and goats, indicating the broad distribution of this pathogenic clone in ruminants. These results provide strong molecular and epidemiological evidence for zoonotic transmission of this emergent clone from ruminants to humans and indicate thatC. jejuniclone SA is an important threat to public health.
Mutational Robustness of an RNA Virus Influences Sensitivity to Lethal Mutagenesis
Authors: Graci Jason D. , Gnädig Nina F. , Galarraga Jessica E. , Castro Christian , Vignuzzi Marco , Cameron Craig E. 
Published: December 2011

ABSTRACT
The ability to extinguish a viral population of fixed reproductive capacity by causing small changes in the mutation rate is referred to as lethal mutagenesis and is a corollary of population genetics theory. Here we show that coxsackievirus B3 (CVB3) exhibits reduced mutational robustness relative to poliovirus, manifesting in enhanced sensitivity of CVB3 to lethal mutagens that is dependent on the size of the viral population. We suggest that mutational robustness may be a useful measure of the sensitivity of a virus to lethal mutagenesis.
Interactions of the Cytoplasmic Domain of Sindbis Virus E2 with Nucleocapsid Cores Promote Alphavirus Budding
Authors: Jose Joyce , Przybyla Laralynne , Edwards Thomas J. , Perera Rushika , Burgner John W. , Kuhn Richard J. 
Published: December 2011

ABSTRACT

Alphavirus budding from the plasma membrane occurs through the specific interaction of the nucleocapsid core with the cytoplasmic domain of the E2 glycoprotein (cdE2). Structural studies of the Sindbis virus capsid protein (CP) have suggested that these critical interactions are mediated by the binding of cdE2 into a hydrophobic pocket in the CP. Several molecular genetic studies have implicated amino acids Y400 and L402 in cdE2 as important for the budding of alphaviruses. In this study, we characterized the role of cdE2 residues in structural polyprotein processing, glycoprotein transport, and capsid interactions. Along with hydrophobic residues, charged residues in the N terminus of cdE2 were critical for the effective interaction of cores with cdE2, a process required for virus budding. Mutations in the C-terminal signal sequence region of cdE2 affected E2 protein transport to the plasma membrane, while nonbudding mutants that were defective in cdE2-CP interaction accumulated E2 on the plasma membrane. The interaction of cdE2 with cytoplasmic cores purified from infected cells and
in vitro
-assembled core-like particles suggests that cdE2 interacts with assembled cores to mediate budding. We hypothesize that these cdE2 interactions induce a change in the organization of the nucleocapsid core upon binding leading to particle budding and priming of the nucleocapsid cores for disassembly that is required for virus infection.
Cellular Transcription Factors Induced in Trigeminal Ganglia during Dexamethasone-Induced Reactivation from Latency Stimulate Bovine Herpesvirus 1 Productive Infection and Certain Viral Promoters
Authors: Workman Aspen , Eudy James , Smith Lynette , Frizzo da Silva Leticia , Sinani Devis , Bricker Halie , Cook Emily , Doster Alan , Jones Clinton 
Published: December 2011

ABSTRACTBovine herpesvirus 1 (BHV-1), an alphaherpesvirinae subfamily member, establishes latency in sensory neurons. Elevated corticosteroid levels, due to stress, reproducibly triggers reactivation from latency in the field. A single intravenous injection of the synthetic corticosteroid dexamethasone (DEX) to latently infected calves consistently induces reactivation from latency. Lytic cycle viral gene expression is detected in sensory neurons within 6 h after DEX treatment of latently infected calves. These observations suggested that DEX stimulated expression of cellular genes leads to lytic cycle viral gene expression and productive infection. In this study, a commercially available assay—Bovine Gene Chip—was used to compare cellular gene expression in the trigeminal ganglia (TG) of calves latently infected with BHV-1 versus DEX-treated animals. Relative to TG prepared from latently infected calves, 11 cellular genes were induced more than 10-fold 3 h after DEX treatment. Pentraxin three, a regulator of innate immunity and neurodegeneration, was stimulated 35- to 63-fold after 3 or 6 h of DEX treatment. Two transcription factors, promyelocytic leukemia zinc finger (PLZF) and Slug were induced more than 15-fold 3 h after DEX treatment. PLZF or Slug stimulated productive infection 20- or 5-fold, respectively, and Slug stimulated the late glycoprotein C promoter more than 10-fold. Additional DEX-induced transcription factors also stimulated productive infection and certain viral promoters. These studies suggest that DEX-inducible cellular transcription factors and/or signaling pathways stimulate lytic cycle viral gene expression, which subsequently leads to successful reactivation from latency in a small subset of latently infected neurons.
The Ecology, Genetic Diversity, and Phylogeny of Huaiyangshan Virus in China
Authors: Zhang Yong-Zhen , Zhou Dun-Jin , Qin Xin-Cheng , Tian Jun-Hua , Xiong Yanwen , Wang Jian-Bo , Chen Xiao-Ping , Gao Dong-Ya , He Yong-Wen , Jin Dong , Sun Qiangzheng , Guo Wen-Ping , Wang Wen , Yu Bin , Li Juan , Dai Yong-An , Li Wei , Peng Jin-Song , Zhang Guo-Bin , Zhang Shaomin , Chen Xiao-Min , Wang Yan , Li Ming-Hui , Lu Xin , Ye Changyun , de Jong Menno D. , Xu Jianguo 
Published: December 2011

ABSTRACT

Surveys were carried out to better understand the tick vector ecology and genetic diversity of Huaiyangshan virus (HYSV) in both regions of endemicity and regions of nonendemicity.
Haemaphysalis longicornis
ticks were dominant in regions of endemicity, while
Rhipicephalus microplus
is more abundant in regions of nonendemicity. HYSV RNA was found in human and both tick species, with greater prevalence in
H. longicornis
and lesser prevalence in
R. microplus
. Phylogenetic analyses indicate that HYSV is a novel species of the genus
Phlebovirus
.
Polymorphic Integrations of an Endogenous Gammaretrovirus in the Mule Deer Genome
Authors: Elleder Daniel , Kim Oekyung , Padhi Abinash , Bankert Jason G. , Simeonov Ivan , Schuster Stephan C. , Wittekindt Nicola E. , Motameny Susanne , Poss Mary 
Published: December 2011

ABSTRACT

Endogenous retroviruses constitute a significant genomic fraction in all mammalian species. Typically they are evolutionarily old and fixed in the host species population. Here we report on a novel endogenous gammaretrovirus (CrERVγ; for cervid endogenous gammaretrovirus) in the mule deer (
Odocoileus hemionus
) that is insertionally polymorphic among individuals from the same geographical location, suggesting that it has a more recent evolutionary origin. Using PCR-based methods, we identified seven CrERVγ proviruses and demonstrated that they show various levels of insertional polymorphism in mule deer individuals. One CrERVγ provirus was detected in all mule deer sampled but was absent from white-tailed deer, indicating that this virus originally integrated after the split of the two species, which occurred approximately one million years ago. There are, on average, 100 CrERVγ copies in the mule deer genome based on quantitative PCR analysis. A CrERVγ provirus was sequenced and contained intact open reading frames (ORFs) for three virus genes. Transcripts were identified covering the entire provirus. CrERVγ forms a distinct branch of the gammaretrovirus phylogeny, with the closest relatives of CrERVγ being endogenous gammaretroviruses from sheep and pig. We demonstrated that white-tailed deer (
Odocoileus virginianus
) and elk (
Cervus canadensis
) DNA contain proviruses that are closely related to mule deer CrERVγ in a conserved region of
pol
; more distantly related sequences can be identified in the genome of another member of the
Cervidae
, the muntjac (
Muntiacus muntjak
). The discovery of a novel transcriptionally active and insertionally polymorphic retrovirus in mammals could provide a useful model system to study the dynamic interaction between the host genome and an invading retrovirus.
Cooperation between c-Met and Focal Adhesion Kinase Family Members in Medulloblastoma and Implications for Therapy
Authors: Guessous Fadila , Yang Yanzhi , Johnson Elizabeth , Marcinkiewicz Lukasz , Smith Matthew , Zhang Ying , Kofman Alexander , Schiff David , Christensen James , Abounader Roger 
Published: December 2011

Abstract
We previously showed the involvement of the tyrosine kinase receptor c-Met in medulloblastoma malignancy. The nonreceptor tyrosine kinases focal adhesion kinase (FAK) and Pyk2 are key players in the progression of different cancers. However, their role in medulloblastoma malignancy is not well understood. In this study, using a protein array approach, we found that c-Met induces FAK and Pyk2 phosphorylation in medulloblastoma cells. We therefore studied the interactions between c-Met and FAK/Pyk2 and their implications for medulloblastoma therapy. We found that c-Met activates FAK and Pyk2 in several medulloblastoma cell lines. We also found that FAK and Pyk2 mediate the malignant effects of c-Met on medulloblastoma cell proliferation, migration, and invasion. On the basis of these findings, we hypothesized that combined c-Met and FAK inhibitions would have additive effects on the inhibition of medulloblastoma malignancy. To test this hypothesis, we assessed the effects on medulloblastoma malignancy parameters of single or combined treatments of medulloblastoma cells with c-Met and FAK small-molecule kinase inhibitors. We found a significant increase in the inhibitory effect of both inhibitors on medulloblastoma cell migration and cell invasion as compared with single inhibitions (P &lt; 0.05). In addition, oral gavage treatment with c-Met inhibitor of mice bearing medulloblastoma xenografts significantly reduced in vivo tumor growth. Therefore, combining c-Met inhibitors with FAK inhibitors constitutes a new potential strategy for medulloblastoma therapy. Altogether, our study describes a role for FAK and Pyk2 in medulloblastoma malignancy, uncovers new interactions between c-Met and FAK/Pyk2, and proposes for the first time combining anti-c-Met and anti-FAK inhibitors as a new strategy for medulloblastoma therapy. Mol Cancer Ther; 11(2); 288–97. ©2011 AACR.
Low-Dose Metronomic Oral Dosing of a Prodrug of Gemcitabine (LY2334737) Causes Antitumor Effects in the Absence of Inhibition of Systemic Vasculogenesis
Authors: Francia Giulio , Shaked Yuval , Hashimoto Kae , Sun John , Yin Melissa , Cesta Carolyn , Xu Ping , Man Shan , Hackl Christina , Stewart Julie , Uhlik Mark , Dantzig Anne H. , Foster F. Stuart , Kerbel Robert S. 
Published: December 2011

Abstract
Metronomic chemotherapy refers to the close, regular administration of conventional chemotherapy drugs at relatively low, minimally toxic doses, with no prolonged break periods; it is now showing encouraging results in various phase II clinical trials and is currently undergoing phase III trial evaluation. It is thought to cause antitumor effects primarily by antiangiogenic mechanisms, both locally by targeting endothelial cells of the tumor neovasculature and systemically by effects on bone marrow–derived cells, including circulating endothelial progenitor cells (CEP). Previous studies have shown reduction of CEPs by metronomic administration of a number of different chemotherapeutic drugs, including vinblastine, cyclophosphamide, paclitaxel, topotecan, and tegafur plus uracil (UFT). However in addition to, or even instead of, antiangiogenic effects, metronomic chemotherapy may cause suppression of tumor growth by other mechanisms such as stimulating cytotoxic T-cell responses or by direct antitumor effects. Here we report results evaluating the properties of metronomic administration of an oral prodrug of gemcitabine LY2334737 in nontumor–bearing mice and in preclinical models of human ovarian (SKOV3-13) and breast cancer (LM2-4) xenografts. Through daily gavage (at 6 mg/kg/d), the schedules tested were devoid of toxicity and caused antitumor effects; however, a suppressive effect on CEPs was not detected. Unexpectedly, metronomic LY2334737 administration caused increased blood flow in luciferase-tagged LM2-4 tumor xenografts, and this effect, readily measured using contrast micro-ultrasound, coincided with a relative increase in tumor bioluminescence. These results highlight the possibility of significant antitumor effects mediated by metronomic administration of some chemotherapy drugs without a concomitant inhibition of systemic angiogenesis. Mol Cancer Ther; 11(3); 680–9. ©2011 AACR.
Can the vector space model be used to identify biological entity activities?
Authors: Maciel Wesley D , Faria-Campos Alessandra C , Gonçalves Marcos A , Campos Sérgio VA 
Published: December 2011

Abstract

Background
Biological systems are commonly described as networks of entity interactions. Some interactions are already known and integrate the current knowledge in life sciences. Others remain unknown for long periods of time and are frequently discovered by chance. In this work we present a model to predict these unknown interactions from a textual collection using the vector space model (VSM), a well known and established information retrieval model. We have extended the VSM ability to retrieve information using a transitive closure approach. Our objective is to use the VSM to identify the known interactions from the literature and construct a network. Based on interactions established in the network our model applies the transitive closure in order to predict and rank new interactions.

Results
We have tested and validated our model using a collection of patent claims issued from 1976 to 2005. From 266,528 possible interactions in our network, the model identified 1,027 known interactions and predicted 3,195 new interactions. Iterating the model according to patent issue dates, interactions found in a given past year were often confirmed by patent claims not in the collection and issued in more recent years. Most confirmation patent claims were found at the top 100 new interactions obtained from each subnetwork. We have also found papers on the Web which confirm new inferred interactions. For instance, the best new interaction inferred by our model relates the interaction between the adrenaline neurotransmitter and the androgen receptor gene. We have found a paper that reports the partial dependence of the antiapoptotic effect of adrenaline on androgen receptor.

Conclusions
The VSM extended with a transitive closure approach provides a good way to identify biological interactions from textual collections. Specifically for the context of literature-based discovery, the extended VSM contributes to identify and rank relevant new interactions even if these interactions occcur in only a few documents in the collection. Consequently, we have developed an efficient method for extracting and restricting the best potential results to consider as new advances in life sciences, even when indications of these results are not easily observed from a mass of documents.
Modeling and analysis of cell membrane systems with probabilistic model checking
Authors: Crepalde Mirlaine A , Faria-Campos Alessandra C , Campos Sérgio VA 
Published: December 2011

Abstract

Background
Recently there has been a growing interest in the application of Probabilistic Model Checking (PMC) for the formal specification of biological systems. PMC is able to exhaustively explore all states of a stochastic model and can provide valuable insight into its behavior which are more difficult to see using only traditional methods for system analysis such as deterministic and stochastic simulation. In this work we propose a stochastic modeling for the description and analysis of sodium-potassium exchange pump. The sodium-potassium pump is a membrane transport system presents in all animal cell and capable of moving sodium and potassium ions against their concentration gradient.

Results
We present a quantitative formal specification of the pump mechanism in the PRISM language, taking into consideration a discrete chemistry approach and the Law of Mass Action aspects. We also present an analysis of the system using quantitative properties in order to verify the pump reversibility and understand the pump behavior using trend labels for the transition rates of the pump reactions.

Conclusions
Probabilistic model checking can be used along with other well established approaches such as simulation and differential equations to better understand pump behavior. Using PMC we can determine if specific events happen such as the potassium outside the cell ends in all model traces. We can also have a more detailed perspective on its behavior such as determining its reversibility and why its normal operation becomes slow over time. This knowledge can be used to direct experimental research and make it more efficient, leading to faster and more accurate scientific discoveries.