bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular and Cellular Characterization of a Salmonella enterica Serovar Paratyphi A Outbreak Strain and the Human Immune Response to Infection
Authors: Gal-Mor Ohad , Suez Jotham , Elhadad Dana , Porwollik Steffen , Leshem Eyal , Valinsky Lea , McClelland Michael , Schwartz Eliezer , Rahav Galia 
Published: December 2011

ABSTRACT

Enteric fever is an invasive life-threatening systemic disease caused by the
Salmonella enterica
human-adapted serovars Typhi and Paratyphi. Increasing incidence of infections with
Salmonella enterica
serovar Paratyphi A and the spreading of its antibiotic-resistant derivates pose a significant health concern in some areas of the world. Herein, we describe a molecular and phenotypic characterization of an
S
. Paratyphi A strain accounted for a recent paratyphoid outbreak in Nepal that affected at least 37 travelers. Pulsed-field gel electrophoresis analysis of the outbreak isolates revealed one genetic clone (pulsotype), confirming a single infecting source. Genetic profiling of the outbreak strain demonstrated the contribution of specific bacteriophages as a prime source of genetic diversity among clinical isolates of
S
. Paratyphi A. Phenotypic characterization in comparison with the
S
. Paratyphi A ATCC 9150 reference sequenced strain showed differences in flagellar morphology and increased abilities of the outbreak strain with respect to its motility, invasion into nonphagocytic cells, intracellular multiplication, survival within macrophages, and higher induction of interleukin-8 (IL-8) secreted by host cells. Collectively, these differences suggest an enhanced virulence potential of this strain and demonstrate an interesting phenotypic variation among
S
. Paratyphi A isolates.
In vivo
profiling of 16 inflammatory cytokines in patients infected with the outbreak strain revealed a common profile of a remarkable gamma interferon (IFN-γ) induction together with elevated concentrations of tumor necrosis factor alpha (TNF-α), IL-6, IL-8, IL-10, and IL-15, but not IL-12, which was previously demonstrated as elevated in nontyphoidal
Salmonella
infections. This apparent profile implies a distinct immune response to paratyphoid infections.
Antibody Breadth and Protective Efficacy Are Increased by Vaccination with Computationally Optimized Hemagglutinin but Not with Polyvalent Hemagglutinin-Based H5N1 Virus-Like Particle Vaccines
Authors: Giles Brendan M. , Bissel Stephanie J. , DeAlmeida Dilhari R. , Wiley Clayton A. , Ross Ted M. 
Published: December 2011

ABSTRACT
One of the challenges for developing an H5N1 influenza vaccine is the diversity of antigenically distinct isolates within this subtype. Previously, our group described a novel hemagglutinin (HA) derived from a methodology termed computationally optimized broadly reactive antigen (COBRA). This COBRA HA, when used as an immunogen, elicits a broad antibody response against H5N1 isolates from different clades. In this report, the immune responses elicited by the COBRA HA virus-like particle (VLP) vaccine were compared to responses elicited by a mixture of VLPs expressing representative HA molecules from clade 2.1, 2.2, and 2.3 primary H5N1 isolates (polyvalent). The COBRA HA VLP vaccine elicited higher-titer antibodies to a panel of H5N1 HA proteins than did the other VLPs. Both COBRA and polyvalent vaccines protected vaccinated mice and ferrets from experimental infection with highly lethal H5N1 influenza viruses, but COBRA-vaccinated animals had decreased viral replication, less inflammation in the lungs of mice, and reduced virus recovery in ferret nasal washes. Both vaccines had similar cellular responses postchallenge, indicating that higher-titer serum antibodies likely restrict the duration of viral replication. Furthermore, passively transferred immune serum from the COBRA HA VLP-vaccinated mice protected recipient animals more efficiently than immune serum from polyvalent-vaccinated mice. This is the first report comparing these two vaccine strategies. The single COBRA HA antigen elicited a broader antibody response and reduced morbidity and viral titers more effectively than a polyvalent mixture of primary H5N1 HA antigens.
Enteric Disease in Dogs Naturally Infected by a Novel Canine Astrovirus
Authors: Martella V. , Moschidou P. , Catella C. , Larocca V. , Pinto P. , Losurdo M. , Corrente M. , Lorusso E. , Bànyai K. , Decaro N. , Lavazza A. , Buonavoglia C. 
Published: December 2011

ABSTRACT
Infection by a novel canine astrovirus was associated with gastroenteritis in two dogs. The virus displayed 70.3 to 73.9% amino acid identity to other canine astroviruses in the full-length capsid. Specific antibodies were detected in the convalescent-phase sera of the dogs, indicating seroconversion. Also, the virus appeared weakly related antigenically to the prototype canine astrovirus isolate ITA/2008/Bari.
Oral Streptococcal Bacteremia in Hospitalized Patients: Taxonomic Identification and Clinical Characterization
Authors: Kitten Todd , Munro Cindy L. , Zollar Nicai Q. , Lee Sehmi P. , Patel Resham D. 
Published: December 2011

ABSTRACT

Oral streptococci have been associated with systemic diseases, including infective endocarditis and neutropenic bacteremia. We analyzed 58 recent oral streptococcal bloodstream isolates, and we obtained clinical and demographic data for source patients. The
sodA
gene was found to be a better target than the 16S-23S rRNA internal transcribed spacer for DNA sequence-based species identification. Together,
Streptococcus mitis
and
Streptococcus oralis
were significantly more likely than the 12 combined remaining species to be isolated from neutropenic patients.
Is sports safety policy being translated into practice: what can be learnt from the Australian rugby union Mayday procedure?
Authors: Poulos Roslyn G , Donaldson Alex 
Published: December 2011

AimTo investigate the level of translation of the Australian Rugby Union ‘Mayday’ safety procedure into practice among community rugby union coaches in New South Wales (Australia).MethodsAll registered coaches of senior community rugby union teams in five zones/associations in the north-eastern region of the state were invited to complete a short online questionnaire at the end of the 2010 rugby season. The questionnaire was designed around the five RE-AIMdimensions and assessed: Reach, perceived Effectiveness, Adoption, Implementation and Maintenance of the Mayday procedure.ResultsSeventy (39%) coaches participated. There was a high level of awareness of the Mayday procedure, and most coaches believed it was effective in preventing injuries. The majority reported training their players in the procedure, although training was generally infrequent. Coaches were confident that their own players could implement the procedure appropriately if required to do so, but less confident that other teams or referees could do so. Barriers to providing training included not enough players at training, players not taking training seriously and technical difficulties (eg, verbalisation of instructions for physical tasks).ConclusionThe findings suggest that the translation of the Mayday ‘policy’ could be improved by building individual coach, and club or zone organisational capacity by ensuring that coaches have the resources and skills in ‘how’ to train their players to complement their existing knowledge on ‘what’ to train them; setting expectations that encourage coaches to provide regular training for players; and regular monitoring of player competency to perform the procedure appropriately.
EGFR Exon 19 Insertions: A New Family of Sensitizing EGFR Mutations in Lung Adenocarcinoma
Authors: He Mai , Capelletti Marzia , Nafa Khedoudja , Yun Cai-Hong , Arcila Maria E. , Miller Vincent A. , Ginsberg Michelle S. , Zhao Binsheng , Kris Mark G. , Eck Michael J. , Jänne Pasi A. , Ladanyi Marc , Oxnard Geoffrey R. 
Published: December 2011

Abstract
Purpose: Epidermal growth factor receptor (EGFR) genotyping is now standard in the management of advanced lung adenocarcinoma, as this biomarker predicts marked benefit from treatment with EGFR tyrosine kinase inhibitors (TKI). EGFR exon 19 insertions are a poorly described family of EGFR mutations, and their association with EGFR-TKI sensitivity in lung adenocarcinoma is uncertain.
Experimental Design: Patients with lung cancers harboring EGFR exon 19 insertions were studied. The predicted effects of the insertions on the structure of the EGFR protein were examined, and EGFR exon 19 insertions were introduced into Ba/F3 cells to assess oncogenicity and in vitro sensitivity to EGFR-TKIs. In patients receiving TKI, response magnitude was assessed with serial computed tomographic (CT) measurement.
Results: Twelve tumors harboring EGFR exon 19 insertions were identified; patients were predominately female (92%) and never-smokers (75%). The 11 specimens available for full sequencing all showed an 18-bp insertion that resulted in the substitution of a Pro for Leu at residue 747. The mutant EGFR transformed the Ba/F3 cells, which were then sensitive to EGFR-TKI. Six patients with measurable disease received TKI and five had a response on serial CT.
Conclusions: EGFR exon 19 insertions are a newly appreciated family of EGFR-TKI–sensitizing mutations, and patients with tumors harboring these mutations should be treated with EGFR-TKI. While these mutations may be missed through the use of some mutation-specific assays, the addition of PCR product size analysis to multigene assays allows sensitive detection of both exon 19 insertion and deletion mutations. Clin Cancer Res; 18(6); 1790–7. ©2011 AACR.
Pseudohyperkalemia in a patient with chronic lymphoblastic leukemia and tumor lysis syndrome
Authors: Kintzel Polly E , Scott William L 
Published: December 2011

Purpose: Recognition of pseudohyperkalemia is essential to prevent medical mismanagement of erroneous hyperkalemia. The purpose of this case is to describe pseudohyperkalemia attributed to malignant leucocytosis in a patient with chronic lymphoblastic leukemia and tumor lysis syndrome. Methods for determination of pseudohyperkalemia are discussed. Summary: A 75-year-old male with progressive chronic lymphoblastic leukemia was hospitalized for medical evaluation and chemotherapy administration. Notable laboratory findings included white blood cell count of 479 × 103 cells/µL (4.00 × 103 cells/µL–10.80 × 103 cells/µL) with 95% lymphocytes (20%–50%) and 5% blasts (zero) present in the differential, serum potassium 9.8 mM/L (3.4 mM/L–5.0 mM/L), uric acid of 11.8 mg/dL (3.5 mg/dL–8.0 mg/dL), serum creatinine 1.47 mg/dL (0.60 mg/dL–1.30 mg/dL), and lactate dehydrogenase of 2529 IU/L (100 IU/L–220 IU/L). The patient was anemic (Hb 7.6 g/dL (14.0 g/dL–18.0 g/dL)) and thrombocytopenic (17 × 103 platelets/μL (140 × 103 platelets/μL–400 × 103 platelets/μL)). There were no electrocardiographic findings indicating systemic hyperkalemia. Repeat analysis of the blood potassium level using a heparinized tube assayed immediately after specimen collection demonstrated a plasma potassium level 4.1 mM/L. Subsequent analysis of specimens using similar methodology demonstrated potassium results within the normal limits despite continued laboratory evidence of pseudohyperkalemia. Based on the patient’s conscious and interactive condition, ECG findings, and normal plasma potassium level following immediate analysis, the diagnosis of pseudohyperkalemia was made. Laboratory findings of pseudohyperkalemia persisted throughout the period of leukocytosis. Conclusion: This case describes pseudohyperkalemia attributed to malignant leucocytosis in a patient with chronic lymphoblastic leukemia (CLL). Practitioners should consider pseudohyperkalemia as the underlying cause of elevated potassium levels in patients with malignant leucocytosis who do not have signs or symptoms of systemic hyperkalemia.
Clinical Outcomes of Characterized Chondrocyte Implantation
Authors: Vanlauwe Johan , Huylebroek José , Van Der Bauwhede Jan , Saris Daniël , Veeckman Geert , Bobic Vladimir , Victor Jan , Almqvist Karl Fredrik , Verdonk Peter , Fortems Yves , Van Lommel Nel , Haazen Ludo 
Published: December 2011

Objective: To assess the clinical outcome of patients treated with autologous chondrocyte implantation using ChondroCelect in daily practice. Methods: The study is a cross-sectional analysis of an open-label, noninterventional cohort. The setting was a compassionate use program, involving 43 orthopaedic centers in 7 European countries. The participants were patients treated with ChondroCelect between October 13, 2004 and July 2, 2008. The measurements used were Clinical Global Impression–Improvement and –Efficacy and solicited adverse event reports. Results: Safety data were collected from 334 patients (90.3%), and effectiveness data were from 282 (76.2%) of the 370 patients treated. Mean age at baseline was 33.6 years (range, 12-57 years), 57% were male, and mean body mass index was 25 kg/m2. Mean follow-up was 2.2 years (range, 0.4-4.1 years). A femoral condyle lesion was reported in 66% (288/379) and a patellar lesion in 19% (84/379). Mean lesion size was 3.5 cm2; a collagen membrane was used in 92.4% (328/355). A therapeutic effect was reported in 89% (234/264) of patients overall and in 87% (40/46) of patellar lesion patients. Rates of much or very much improved patients were similar in patients with short- (<18 months: 71% [115/163]) and long-term follow-up (>18 months: 68% [70/103]) ( P = 0.68) and were independent of lesion size (>4 cm2: 75.5% [37/49]; ≤4 cm2: 67.7% [111/164]) ( P = 0.38). Adverse events were similar to those reported in the randomized trial with the same product, with more arthrofibrosis, more reduced joint mobility, and more crepitations reported in patellar lesions. Overall, less cartilage hypertrophy was noted, probably due to the use of a biological membrane cover. Conclusions: Implantation of ChondroCelect appeared to result in a positive benefit/risk ratio when used in an unselected heterogenous population, irrespective of the follow-up period, lesion size, and type of lesion treated.
Some exponential inequalities for acceptable random variables and complete convergence
Authors: Shen Aiting , Hu Shuhe , Volodin Andrei , Wang Xuejun 
Published: December 2011

Abstract
Some exponential inequalities for a sequence of acceptable random variables are obtained, such as Bernstein-type inequality, Hoeffding-type inequality. The Bernstein-type inequality for acceptable random variables generalizes and improves the corresponding results presented by Yang for NA random variables and Wang et al. for NOD random variables. Using the exponential inequalities, we further study the complete convergence for acceptable random variables.

MSC(2000): 60E15, 60F15.
"Antelope": a hybrid-logic model checker for branching-time Boolean GRN analysis
Authors: Arellano Gustavo , Argil Julián , Azpeitia Eugenio , Benítez Mariana , Carrillo Miguel , Góngora Pedro , Rosenblueth David A , Alvarez-Buylla Elena R 
Published: December 2011

Abstract

Background
In Thomas' formalism for modeling gene regulatory networks (GRNs), branching time, where a state can have more than one possible future, plays a prominent role. By representing a certain degree of unpredictability, branching time can model several important phenomena, such as (a) asynchrony, (b) incompletely specified behavior, and (c) interaction with the environment. Introducing more than one possible future for a state, however, creates a difficulty for ordinary simulators, because infinitely many paths may appear, limiting ordinary simulators to statistical conclusions. Model checkers for branching time, by contrast, are able to prove properties in the presence of infinitely many paths.

Results
We have developed Antelope ("Analysis of Networks through TEmporal-LOgic sPEcifications", http://turing.iimas.unam.mx:8080/AntelopeWEB/), a model checker for analyzing and constructing Boolean GRNs. Currently, software systems for Boolean GRNs use branching time almost exclusively for asynchrony. Antelope, by contrast, also uses branching time for incompletely specified behavior and environment interaction. We show the usefulness of modeling these two phenomena in the development of a Boolean GRN of the Arabidopsis thaliana root stem cell niche.
There are two obstacles to a direct approach when applying model checking to Boolean GRN analysis. First, ordinary model checkers normally only verify whether or not a given set of model states has a given property. In comparison, a model checker for Boolean GRNs is preferable if it reports the set of states having a desired property. Second, for efficiency, the expressiveness of many model checkers is limited, resulting in the inability to express some interesting properties of Boolean GRNs.

Antelope tries to overcome these two drawbacks: Apart from reporting the set of all states having a given property, our model checker can express, at the expense of efficiency, some properties that ordinary model checkers (e.g., NuSMV) cannot. This additional expressiveness is achieved by employing a logic extending the standard Computation-Tree Logic (CTL) with hybrid-logic operators.

Conclusions
We illustrate the advantages of Antelope when (a) modeling incomplete networks and environment interaction, (b) exhibiting the set of all states having a given property, and (c) representing Boolean GRN properties with hybrid CTL.
H2B ubiquitylation is part of chromatin architecture that marks exon-intron structure in budding yeast
Authors: Shieh Grace S , Pan Chin-Hua , Wu Jia-Hong , Sun Yun-Ju , Wang Chia-Chang , Hsiao Wei-Chun , Lin Chia-Yeh , Tung Luh , Chang Tien-Hsien , Fleming Alastair B , Hillyer Cory , Lo Yi-Chen , Berger Shelley L , Osley Mary Ann , Kao Cheng-Fu 
Published: December 2011

Abstract

Background
The packaging of DNA into chromatin regulates transcription from initiation through 3' end processing. One aspect of transcription in which chromatin plays a poorly understood role is the co-transcriptional splicing of pre-mRNA.

Results
Here we provide evidence that H2B monoubiquitylation (H2BK123ub1) marks introns in Saccharomyces cerevisiae. A genome-wide map of H2BK123ub1 in this organism reveals that this modification is enriched in coding regions and that its levels peak at the transcribed regions of two characteristic subgroups of genes. First, long genes are more likely to have higher levels of H2BK123ub1, correlating with the postulated role of this modification in preventing cryptic transcription initiation in ORFs. Second, genes that are highly transcribed also have high levels of H2BK123ub1, including the ribosomal protein genes, which comprise the majority of intron-containing genes in yeast. H2BK123ub1 is also a feature of introns in the yeast genome, and the disruption of this modification alters the intragenic distribution of H3 trimethylation on lysine 36 (H3K36me3), which functionally correlates with alternative RNA splicing in humans. In addition, the deletion of genes encoding the U2 snRNP subunits, Lea1 or Msl1, in combination with an htb-K123R mutation, leads to synthetic lethality.

Conclusion
These data suggest that H2BK123ub1 facilitates cross talk between chromatin and pre-mRNA splicing by modulating the distribution of intronic and exonic histone modifications.
Using RNA-seq to determine the transcriptional landscape and the hypoxic response of the pathogenic yeast Candida parapsilosis
Authors: Guida Alessandro , Lindstädt Claudia , Maguire Sarah L , Ding Chen , Higgins Desmond G , Corton Nicola J , Berriman Matthew , Butler Geraldine 
Published: December 2011

Abstract

Background

Candida parapsilosis is one of the most common causes of Candida infection worldwide. However, the genome sequence annotation was made without experimental validation and little is known about the transcriptional landscape. The transcriptional response of C. parapsilosis to hypoxic (low oxygen) conditions, such as those encountered in the host, is also relatively unexplored.

Results
We used next generation sequencing (RNA-seq) to determine the transcriptional profile of C. parapsilosis growing in several conditions including different media, temperatures and oxygen concentrations. We identified 395 novel protein-coding sequences that had not previously been annotated. We removed > 300 unsupported gene models, and corrected approximately 900. We mapped the 5' and 3' UTR for thousands of genes. We also identified 422 introns, including two introns in the 3' UTR of one gene. This is the first report of 3' UTR introns in the Saccharomycotina. Comparing the introns in coding sequences with other species shows that small numbers have been gained and lost throughout evolution. Our analysis also identified a number of novel transcriptional active regions (nTARs). We used both RNA-seq and microarray analysis to determine the transcriptional profile of cells grown in normoxic and hypoxic conditions in rich media, and we showed that there was a high correlation between the approaches. We also generated a knockout of the UPC2 transcriptional regulator, and we found that similar to C. albicans, Upc2 is required for conferring resistance to azole drugs, and for regulation of expression of the ergosterol pathway in hypoxia.

Conclusion
We provide the first detailed annotation of the C. parapsilosis genome, based on gene predictions and transcriptional analysis. We identified a number of novel ORFs and other transcribed regions, and detected transcripts from approximately 90% of the annotated protein coding genes. We found that the transcription factor Upc2 role has a conserved role as a major regulator of the hypoxic response in C. parapsilosis and C. albicans.
FReDoWS: a method to automate molecular docking simulations with explicit receptor flexibility and snapshots selection
Authors: Machado Karina S , Schroeder Evelyn K , Ruiz Duncan D , Cohen Elisângela ML , Norberto de Souza Osmar 
Published: December 2011

Abstract

Background

In silico molecular docking is an essential step in modern drug discovery when driven by a well defined macromolecular target. Hence, the process is called structure-based or rational drug design (RDD). In the docking step of RDD the macromolecule or receptor is usually considered a rigid body. However, we know from biology that macromolecules such as enzymes and membrane receptors are inherently flexible. Accounting for this flexibility in molecular docking experiments is not trivial. One possibility, which we call a fully-flexible receptor model, is to use a molecular dynamics simulation trajectory of the receptor to simulate its explicit flexibility. To benefit from this concept, which has been known since 2000, it is essential to develop and improve new tools that enable molecular docking simulations of fully-flexible receptor models.

Results
We have developed a Flexible-Receptor Docking Workflow System (FReDoWS) to automate molecular docking simulations using a fully-flexible receptor model. In addition, it includes a snapshot selection feature to facilitate acceleration the virtual screening of ligands for well defined disease targets. FReDoWS usefulness is demonstrated by investigating the docking of four different ligands to flexible models of Mycobacterium tuberculosis’ wild type InhA enzyme and mutants I21V and I16T. We find that all four ligands bind effectively to this receptor as expected from the literature on similar, but wet experiments.

Conclusions
A work that would usually need the manual execution of many computer programs, and the manipulation of thousands of files, was efficiently and automatically performed by FReDoWS. Its friendly interface allows the user to change the docking and execution parameters. Besides, the snapshot selection feature allowed the acceleration of docking simulations. We expect FReDoWS to help us explore more of the role flexibility plays in receptor-ligand interactions. FReDoWS can be made available upon request to the authors.