bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acquisition of omptin reveals cryptic virulence function of autotransporter YapE in Yersinia pestis
Authors: Lawrenz Matthew B. , Pennington Jarrod , Miller Virginia L. 
Published: May 2013

SummaryAutotransporters, the largest family of secreted proteins in Gram‐negative bacteria, perform a variety of functions, including adherence, cytotoxicity and immune evasion. In Yersinia pestis the autotransporter YapE has adhesive properties and contributes to disease in the mouse model of bubonic plague. Here, we demonstrate that omptin cleavage of Y. pestis YapE is required to mediate bacterial aggregation and adherence to eukaryotic cells. We demonstrate that omptin cleavage is specific for the Y. pestis and Y. pseudotuberculosis YapE orthologues but is not conserved in the Yersinia enterocolitica protein. We also show that cleavage of YapE occurs in Y. pestis but not in the enteric Yersinia species, and requires the omptin Pla (plasminogen activator protease), which is encoded on the Y. pestis‐specific plasmid pPCP1. Together, these data show that post‐translation modification of YapE appears to be specific to Y. pestis, was acquired along with the acquisition of pPCP1 during the divergence of Y. pestis from Y. pseudotuberculosis, and are the first evidence of a novel mechanism to regulate bacterial adherence.
Molecular and structural basis of glutathione import in Gram‐positive bacteria via GshT and the cystine ABC importer TcyBC of Streptococcus mutans
Authors: Vergauwen Bjorn , Verstraete Kenneth , Senadheera Dilani B. , Dansercoer Ann , Cvitkovitch Dennis G. , Guédon Eric , Savvides Savvas N. 
Published: May 2013

SummaryGlutathione (GSH) protects cells against oxidative injury and maintains a range of vital functions across all branches of life. Despite recent advances in our understanding of the transport mechanisms responsible for maintaining the spatiotemporal homeostasis of GSH and its conjugates in eukaryotes and Gram‐negative bacteria, the molecular and structural basis of GSH import into Gram‐positive bacteria has remained largely uncharacterized. Here, we employ genetic, biochemical and structural studies to investigate a possible glutathione import axis in Streptococcus mutans, an organism that has hitherto served as a model system. We show that GshT, a type 3 solute binding protein, displays physiologically relevant affinity for GSH and glutathione disulfide (GSSG). The crystal structure of GshT in complex with GSSG reveals a collapsed structure whereby the GS‐I‐leg of GSSG is accommodated tightly via extensive interactions contributed by the N‐ and C‐terminal lobes of GshT, while the GS‐II leg extends to the solvent. This can explain the ligand promiscuity of GshT in terms of binding glutathione analogues with substitutions at the cysteine‐sulfur or the glycine‐carboxylate. Finally, we show that GshT primes glutathione import via the l‐cystine ABC transporter TcyBC, a membrane permease, which had previously exclusively been associated with the transport of l‐cystine.
Impact of a Pregabalin Step Therapy Policy Among Medicare Advantage Beneficiaries
Authors: Suehs Brandon T. , Louder Anthony , Udall Margarita , Cappelleri Joseph C. , Joshi Ashish V. , Patel Nick C. 
Published: May 2013

AbstractBackgroundManaged healthcare organizations often utilize formulary management strategies such as prior authorization and step therapy to guide appropriate medication use and to control medication expenditures. The objective of this study was to examine clinical and economic outcomes associated with implementation of a pregabalin step therapy (ST) policy among Medicare Advantage Prescription Drug (MAPD) members.MethodsPharmacy and medical claims data from Humana (restricted cohort; ST policy implemented 01/01/2009) and Thomson Reuters MarketScan® (unrestricted cohort) were analyzed for MAPD members aged 65 to 89 years receiving treatment for painful diabetic peripheral neuropathy (pDPN), postherpetic neuralgia (PHN) or fibromyalgia (FM). Difference‐in‐differences (DID) was used to examine year‐over‐year changes in disease‐related and all‐cause utilization and costs. Regression analyses examined medication utilization and healthcare expenditures after controlling for between‐group compositional differences.ResultsWe identified 13,911 members in the restricted cohort and matched to members from unrestricted health plans. FM (51.0%) and pDPN (41.8%) were the most common diagnoses. Members in the unrestricted cohort were older and had a greater level of comorbidity than members in the restricted cohort. The restricted cohort demonstrated greater year‐over‐year decrease in pregabalin utilization and increase in year‐over‐year gabapentin utilization compared with the unrestricted cohort. ST restriction was associated with an increase in disease‐related pharmacy costs and a decrease in total medical costs for the restricted cohort compared with the unrestricted cohort. There was no difference between cohorts in total healthcare cost.ConclusionAfter controlling for differences in age and comorbidity burden between the groups, implementation of a pregabalin ST restriction was associated with increased disease‐related pharmacy costs and decreased total medical costs; however, there was no net difference in total healthcare cost or total pharmacy cost.
Pathogenic mechanisms of influenza A(H1N1)pdm09 infection elucidated on gene expression profiling
Authors: Yamashita Nobuko , Tsukahara Hirokazu , Tsuge Mitsuru , Nagaoka Yoshiharu , Yashiro Masato , Saito Yukie , Fujii Yosuke , Oka Takashi , Morishima Tsuneo 
Published: May 2013

AbstractBackgroundThe pathogenic mechanisms underlying influenza A(H1N1)pdm09‐associated central nervous system (CNS) manifestations and pneumonia remain unclear. This study examined A(H1N1)pdm09 host responses using gene expression profiles of patients’ peripheral blood.MethodsSixteen A(H1N1)pdm09‐infected children in three groups were examined: a CNS group, with convulsion and altered consciousness (n = 6); a pneumonia (Pneu) group (n = 5); and a group of infected control patients (n = 5). The signal ratios of the acute to recovery phases in CNS or Pneu were analyzed versus those of the control.ResultsThe CNS (619 transcripts) and Pneu (656 transcripts) groups had significantly increased signal ratios compared to the control group. Regarding the increased ratios of transcripts shown by multiple probes, contactin‐associated protein‐like 3 transcripts, oleoyl‐ACP hydrolase transcripts, and interleukin 1 type 1 receptor were observed in CNS and Pneu. Increased ratios of prostaglandin‐endoperoxide synthase 2 and α‐synuclein were characteristic of CNS. Alkaline phosphatase and the Fc fragment of IgA receptor were characteristic of Pneu. Regarding enriched gene ontology terms, ‘response to lipopolysaccharide’, ‘innate immune response’, and ‘intrinsic to membrane’ were observed commonly in CNS and Pneu. Enriched gene ontology terms related to ‘hemoglobin’ and ‘hemostasis’ were, respectively, characteristic of CNS and Pneu.ConclusionThese symptom‐associated transcripts might be some clues to the pathogenesis of the A(H1N1)pdm09 infection.
Optimization of Ram Semen Cryopreservation Using a Chemically Defined Soybean Lecithin‐Based Extender
Authors: Emamverdi M , Zhandi M , Zare Shahneh A , Sharafi M , Akbari‐Sharif A 
Published: May 2013

ContentsThe purpose of the present study was to investigate the effects of a chemically defined soybean lecithin‐based semen extender as a substitute for egg yolk‐based extenders in ram semen cryopreservation. In this study, 28 ejaculates were collected from fourZandi rams in the breeding season and then pooled together. The pooled semen was divided into six equal aliquots and diluted with six different extenders: (i) Tris‐based extender (TE) containing 0.5% (w/v) soybean lecithin (SL0.5), (ii)TEcontaining 1% (w/v) soybean lecithin (SL1), (iii)TEcontaining 1.5% (w/v) soybean lecithin (SL1.5), (iv)TEcontaining 2% (w/v) soybean lecithin (SL2), (v)TEcontaining 2.5% (w/v) soybean lecithin (SL2.5) and (vi)TEcontaining 20% (v/v) egg yolk (EYT). After thawing, sperm motility and motion parameters, plasma membrane and acrosome integrity, apoptosis status and mitochondrial activity were evaluated. The results shown that total and progressive motility (54.43 ± 1.33% and 25.43 ± 0.96%, respectively) were significantly higher inSL1.5 when compared to other semen extenders. Sperm motion parameters (VAP,VSL,VCL,ALHandSTR) were significantly higher inSL1.5 compared to other extender, with the exception ofSL1 extender. Plasma membrane integrity (48.86 ± 1.38%) was significantly higher inSL1.5 when compared to other semen extenders. Also, percentage of spermatozoa with intact acrosome inSL1.5 (85.35 ± 2.19%) extender was significantly higher than that inSL0.5,SL2.5 andEYTextenders. The results showed that the proportion of live post‐thawed sperm was significantly increased inSL1.5 extender compared toSL0.5,SL2 andEYTextenders. In addition,SL1,SL1.5 andSL2.5 extenders resulted in significantly lower percentage of early‐apoptotic sperm than that inEYTextender. There were no significant differences in different semen extenders for percentage of post‐thawed necrotic and late‐apoptotic spermatozoa. Also, the results indicated that there are slight differences for percentage of live spermatozoa with active mitochondria between extenders. In conclusion,SL1.5 extender was better than other extenders in mostin vitroevaluated sperm parameters.
Identifying the Magnitude and Location of a Load on a Slender Beam Using a Strain Gauge Based Force Transducer
Authors: Bednarz E. T. , Zhu W. D. , Smith S. A. 
Published: May 2013

ABSTRACTA unique strain gauge based method is developed to identify the magnitude and location of a load on a slender beam with variable cross sections, and pinned, firm rest, soft rest, pinned‐fixed, and fixed boundary conditions. Four uniaxial strain gauges are mounted to the bottom surface of the beam, and the bending moment diagram of the beam can be constructed using measured strains on the beam. By combining individually scaled strain gauge outputs, the magnitude and location of the load can be accurately identified. The strain gauge based force transducer methodology is experimentally validated on prismatic beams with firm rest, soft rest, firm rest‐fixed, and fixed boundary conditions, and a continuously tapered beam with rest boundary conditions. The force transducer methodology is independent of the boundary conditions of the beam, and the error from strain gauge drift due to uniform thermal expansion on a prismatic beam can cancel out.
Streptococcus sanguinis Isolate Displaying a Phenotype with Cross-Resistance to Several rRNA-Targeting Agents
Authors: Mendes Rodrigo E. , Deshpande Lalitagauri M. , Kim Jihye , Myers Debra S. , Ross James E. , Jones Ronald N. 
Published: May 2013

ABSTRACT

This study describes a clinical case of a 71-year-old male with a history of ischemic cardiomyopathy after left ventricular assist device (LVAD) endocarditis caused by methicillin-resistant
Staphylococcus epidermidis
(MRSE) and a rare linezolid-resistant
Streptococcus sanguinis
strain (MIC, 32 μg/ml). The patient received courses of several antimicrobial agents, including linezolid for 79 days. The
S. sanguinis
strain had mutations in the 23S rRNA (T2211C, T2406C, G2576T, C2610T) and an amino acid substitution (N56D) in L22 and exhibited cross-resistance to ribosome-targeting agents.
Microscopic Examination of Gallbladder Stones Improves Rate of Detection of Clonorchis sinensis Infection
Authors: Qiao Tie , Ma Rui-hong , Luo Xiao-bing , Zheng Pei-ming , Luo Zhen-liang , Yang Liu-qing 
Published: May 2013

ABSTRACT

To improve the rate of detection of
Clonorchis sinensis
infection, we compared different specimens from patients with cholecystolithiasis. Feces, gallbladder bile, and gallbladder stones collected from 179 consecutive patients with cholecystolithiasis underwent microscopic examination, and according to the results, 30 egg-positive and 30 egg-negative fecal, gallbladder bile, and gallbladder stone specimens, respectively, underwent real-time fluorescent PCR. The detection rates of eggs in feces, bile, and gallbladder stones were 30.7%, 44.7%, and 69.8%, respectively, and the differences were statistically significant (
P
< 0.01). The PCR results confirmed that the eggs in the specimens were
C. sinensis
eggs. Eggs in the feces were “fresh” and in the gallbladder stones were “old.” Microscopic examination of gallbladder stones may improve the detection rates of
C. sinensis
infection, which is important for developing individualized treatments to prevent the recurrence of gallbladder stones and to prevent the occurrence of severe liver damage and cholangiocarcinoma.
Adult Invasive and Noninvasive Infections Due to Streptococcus dysgalactiae subsp. equisimilis in France from 2006 to 2010
Authors: Loubinoux Julien , Plainvert Céline , Collobert Gislène , Touak Gérald , Bouvet Anne , Poyart Claire 
Published: May 2013

ABSTRACT

We characterized 182
Streptococcus dysgalactiae
subsp.
equisimilis
isolates and analyzed the epidemiological data on the corresponding infections.
stG6
,
stG485
, and
stG6792
were the 3 most prevalent invasive
emm
types among the 27 different
emm
types recovered. High rates of antimicrobial resistance were observed for macrolides (26.4%) and tetracycline (34.6%).
Reverse Genetics Identifies the Product of Open Reading Frame 4 as an Essential Particle Assembly Factor of Nyamanini Virus
Authors: Herrel Marieke , Haag Lars , Nilsson Josefina , Staeheli Peter , Schneider Urs 
Published: May 2013

ABSTRACT
We established a reverse genetics system for Nyamanini virus (NYMV) and recovered green fluorescent protein (GFP)-expressing virus from full-length cDNA. Using this technology, we assessed the functions of two poorly characterized viral genes. NYMV lacking open reading frame 2 (ORF2) could not be rescued, whereas virus lacking ORF4 was replication competent. ORF4-deficient NYMV readily established a persisting noncytolytic infection but failed to produce infectious viral particles, supporting the view that ORF4 represents an essential factor for NYMV particle assembly.
CD4+and CD8+T-Cell Responses to Latent Antigen EBNA-1 and Lytic Antigen BZLF-1 during Persistent Lymphocryptovirus Infection of Rhesus Macaques
Authors: Leskowitz R. M. , Zhou X. Y. , Villinger F. , Fogg M. H. , Kaur A. , Lieberman P. M. , Wang F. , Ertl H. C. 
Published: May 2013

ABSTRACTEpstein-Barr virus (EBV) infection leads to lifelong viral persistence through its latency in B cells. EBV-specific T cells control reactivations and prevent the development of EBV-associated malignancies in most healthy carriers, but infection can sometimes cause chronic disease and malignant transformation. Epstein-Barr nuclear antigen 1 (EBNA-1) is the only viral protein consistently expressed during all forms of latency and in all EBV-associated malignancies and is a promising target for a therapeutic vaccine. Here, we studied the EBNA-1-specific immune response using the EBV-homologous rhesus lymphocryptovirus (rhLCV) infection in rhesus macaques. We assessed the frequency, phenotype, and cytokine production profiles of rhLCV EBNA-1 (rhEBNA-1)-specific T cells in 15 rhesus macaques and compared them to the lytic antigen of rhLCV BZLF-1 (rhBZLF-1). We were able to detect rhEBNA-1-specific CD4+and/or CD8+T cells in 14 of the 15 animals screened. In comparison, all 15 animals had detectable rhBZLF-1 responses. Most peptide-specific CD4+T cells exhibited a resting phenotype of central memory (TCM), while peptide-specific CD8+T cells showed a more activated phenotype, belonging mainly to the effector cell subset. By comparing our results to the human EBV immune response, we demonstrate that the rhLCV model is a valid system for studying chronic EBV infection and for the preclinical development of therapeutic vaccines.
Structure and Functional Analysis of the Host Recognition Device of Lactococcal Phage Tuc2009
Authors: Collins Barry , Bebeacua Cecilia , Mahony Jennifer , Blangy Stéphanie , Douillard François P. , Veesler David , Cambillau Christian , van Sinderen Douwe 
Published: May 2013

ABSTRACT

Many phages employ a large heteropolymeric organelle located at the tip of the tail, termed the baseplate, for host recognition. Contrast electron microscopy (EM) of the lactococcal phage Tuc2009 baseplate and its host-binding subunits, the so-called tripods, allowed us to obtain a low-resolution structural image of this organelle. Structural comparisons between the baseplate of the related phage TP901-1 and that of Tuc2009 demonstrated that they are highly similar, except for the presence of an additional protein in the Tuc2009 baseplate (BppA
Tuc2009
), which is attached to the top of the Tuc2009 tripod structure. Recombinantly produced Tuc2009 or TP901-1 tripods were shown to bind specifically to their particular host cell surfaces and are capable of almost fully and specifically eliminating Tuc2009 or TP901-1 phage adsorption, respectively. In the case of Tuc2009, such adsorption-blocking ability was reduced in tripods that lacked BppA
Tuc2009
, indicating that this protein increases the binding specificity and/or affinity of the Tuc2009 tripod to its host receptor.
Massive Activation of Archaeal Defense Genes during Viral Infection
Authors: Quax Tessa E. F. , Voet Marleen , Sismeiro Odile , Dillies Marie-Agnes , Jagla Bernd , Coppée Jean-Yves , Sezonov Guennadi , Forterre Patrick , van der Oost John , Lavigne Rob , Prangishvili David 
Published: May 2013

ABSTRACT

Archaeal viruses display unusually high genetic and morphological diversity. Studies of these viruses proved to be instrumental for the expansion of knowledge on viral diversity and evolution. The
Sulfolobus islandicus
rod-shaped virus 2 (SIRV2) is a model to study virus-host interactions in
Archaea
. It is a lytic virus that exploits a unique egress mechanism based on the formation of remarkable pyramidal structures on the host cell envelope. Using whole-transcriptome sequencing, we present here a global map defining host and viral gene expression during the infection cycle of SIRV2 in its hyperthermophilic host
S. islandicus
LAL14/1. This information was used, in combination with a yeast two-hybrid analysis of SIRV2 protein interactions, to advance current understanding of viral gene functions. As a consequence of SIRV2 infection, transcription of more than one-third of
S. islandicus
genes was differentially regulated. While expression of genes involved in cell division decreased, those genes playing a role in antiviral defense were activated on a large scale. Expression of genes belonging to toxin-antitoxin and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas systems was specifically pronounced. The observed different degree of activation of various CRISPR-Cas systems highlights the specialized functions they perform. The information on individual gene expression and activation of antiviral defense systems is expected to aid future studies aimed at detailed understanding of the functions and interplay of these systems
in vivo
.
Role of the Phosphatidylserine Receptor TIM-1 in Enveloped-Virus Entry
Authors: Moller-Tank Sven , Kondratowicz Andrew S. , Davey Robert A. , Rennert Paul D. , Maury Wendy 
Published: May 2013

ABSTRACT
The cell surface receptor T cell immunoglobulin mucin domain 1 (TIM-1) dramatically enhances filovirus infection of epithelial cells. Here, we showed that key phosphatidylserine (PtdSer) binding residues of the TIM-1 IgV domain are critical for Ebola virus (EBOV) entry through direct interaction with PtdSer on the viral envelope. PtdSer liposomes but not phosphatidylcholine liposomes competed with TIM-1 for EBOV pseudovirion binding and transduction. Further, annexin V (AnxV) substituted for the TIM-1 IgV domain, supporting a PtdSer-dependent mechanism. Our findings suggest that TIM-1-dependent uptake of EBOV occurs by apoptotic mimicry. Additionally, TIM-1 enhanced infection of a wide range of enveloped viruses, including alphaviruses and a baculovirus. As further evidence of the critical role of enveloped-virion-associated PtdSer in TIM-1-mediated uptake, TIM-1 enhanced internalization of pseudovirions and virus-like proteins (VLPs) lacking a glycoprotein, providing evidence that TIM-1 and PtdSer-binding receptors can mediate virus uptake independent of a glycoprotein. These results provide evidence for a broad role of TIM-1 as a PtdSer-binding receptor that mediates enveloped-virus uptake. Utilization of PtdSer-binding receptors may explain the wide tropism of many of these viruses and provide new avenues for controlling their virulence.
Recurrent ascending cholangitis due to small intestinal bacterial overgrowth, gastrointestinal dysmotility and an afferent loop
Authors: Harrison Elizabeth , Stokes Wendy , Martin Joanne E , Cooper Sheldon C 
Published: May 2013

SummaryWe report a complex case involving an extremely rare cause of gastrointestinal dysmotility and an afferent loop, which together predisposed to the development of small intestinal bacterial overgrowth. The bacteria subsequently became multi-resistant. As a further consequence of the dysmotility, repeated bile duct reflux occurred despite the afferent loop being unobstructed. This bile duct reflux produced recurrent sepsis through repeated episodes of ascending cholangitis. Ultimately, the patient was referred to a National Small Intestinal Transplant Centre for consideration for enterectomy and subsequent transplantation. We describe the difficulties encountered in managing this unique case and discuss the underlying aetiology.
PRICING EUROPEAN AND AMERICAN OPTIONS IN THE HESTON MODEL WITH ACCELERATED EXPLICIT FINITE DIFFERENCING METHODS
Authors: O'SULLIVAN CONALL , O'SULLIVAN STEPHEN 
Published: May 2013

We present an acceleration technique, effective for explicit finite difference schemes describing diffusive processes with nearly symmetric operators, called Super-Time-Stepping (STS). The technique is applied to the two-factor problem of option pricing under stochastic volatility. It is shown to significantly reduce the severity of the stability constraint known as the Courant-Friedrichs-Lewy condition whilst retaining the simplicity of the chosen underlying explicit method. For European and American put options under Heston's stochastic volatility model we demonstrate degrees of acceleration over standard explicit methods sufficient to achieve comparable, or superior, efficiency to benchmark implicit schemes. We conclude that STS accelerated methods are powerful numerical tools for the pricing of options which inherit the simplicity of explicit methods whilst achieving high accuracy at low computational cost and offer a compelling alternative to conventional implicit techniques.