bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recent developments in gastroesophageal reflux disease and Barrett's esophagus: ANNO 2012
Authors: TYTGAT Guido NJ 
Published: March 2012

The incidence of gastroesophageal reflux disease (GERD) and esophageal columnar metaplasia is rising worldwide. Both mechanical and functional factors perturb the double sphincter barrier at the esophagogastric junction (EGJ). Discovery of the acid pocket is fundamental in understanding postprandial acid reflux. Adding impedencemetry to pH measurements allows detection of non‐acid or weakly acidic reflux. Histologic and endoscopic injury of the squamous mucosa rises from dilation of the intercellular spaces, papillary extension, accentuated intrapapillary looping, red streaks, erosive tissue loss, etc., graded with the Los Angeles system. Seventy percent of patients have no recognizable abnormalities (non‐erosive or neGERD). Treatment of GERD mainly relates to the control of acid secretion but a revival of alginate/antacid obliterating the acid pocket is to be expected. Weaker heartburn control in neGERD is a misnomer because most studies included patients with no evidence of reflux disease. Traditional (delayed‐release) proton pump inhibitors (PPIs) are powerful suppressors of acid secretion but do have limitations such as gradual build up of acid control, weak control of nocturnal acid recovery, possibility of rebound, occasional need for dose escalation, etc.Barrett's esophagus (BE) is endoscopically diagnosed also in the absence of intestinal metaplasia. A prerequisite is the precise location of the EGJ (proximal end of gastric folds, esophageal sphincter pinch, distal extent of palisade vessels). BE is graded with the Prague C & M system. Barrett's cancer develops usually via low‐grade and high‐grade dysplasia. Endoscopic examination may indicate suspicious areas, amenable for targeted biopsy. Otherwise, four quadrant biopsies are obtained when searching for neoplasia. Low‐grade dysplasia, especially when it is multifocal and p53 positive, high‐grade dysplasia and mucosal cancer should be treated with endoscopic resection of the target area, followed by radiofrequency ablation of the adjacent non‐neoplastic columnar mucosa, followed with powerful acid suppressant therapy. The long‐term results of the combination of resection and ablation are exiting and at least comparable to surgical resection.
Non‐inflammatory centrilobular sinusoidal fibrosis in pediatric liver transplant recipients under tacrolimus withdrawal
Authors: Egawa Hiroto , Miyagawa‐Hayashino Aya , Haga Hironori , Teramukai Satoshi , Yoshizawa Atsushi , Ogawa Kohei , Ogura Yasuhiro , Okamoto Shinya , Kaido Toshimi , Uemoto Shinji 
Published: March 2012

Aim:  We hypothesized that non‐inflammatory central sinusoidal fibrosis (NICSF) is a sign of inadequate immunosuppression in children after living‐donor liver transplantation.Methods:  In study 1, liver biopsy specimens of 158 patients who had undergone liver transplantation 10 years before or earlier were examined to study the relationship between NICSF and tacrolimus withdrawal. In study 2, tacrolimus was resumed in 18 patients with NICSF in follow‐up biopsies after tacrolimus withdrawal and the subsequent histological changes were analyzed.Results:  In study 1, after excluding 95 patients with ongoing vascular, biliary and immunological complications, 47 of 63 patients (75%) had NICSF and significant (P = 0.0285) contributing factors were found to be episodes of tacrolimus withdrawal. In study 2, during withdrawal, tacrolimus administration had been discontinued in nine, reduced to once per month in three, twice per month in two, once a week in two and twice a week in two patients, and then finally resumed to daily administration in all. NICSF was scored as 4 in one, 3 in seven, 2 in four and 1 in six patients using modified Dixon's criteria (score, 0–4). After resumption, NICSF was improved in six, unchanged in 11 and aggravated in one patient. C4d deposition was improved in all NICSF‐improved patients. Incidence of positive C4d prior to resumption was significantly greater in improved patients than non‐improved patients (P = 0.0245).Conclusion:  NICSF might be an indicator of inadequate immunosuppression in long‐term followed recipients and its mechanism may be due to immune reactions including humoral immunity.
Elimination half‐life of intravenously administered equine cardiac troponin I in healthy ponies
Authors: KRAUS M. S. , KAUFER B. B. , DAMIANI A. , OSTERRIEDER N. , RISHNIW M. , SCHWARK W. , GELZER A. R. , DIVERS T. J. 
Published: March 2012

SummaryReasons for performing study: To date, no information is available on the true biological elimination half‐life (T1/2) of cardiac troponin I (cTnI) in the equine species. Such data are required to better evaluate the optimal time to acquire the cTnI sample following acute myocardial injury.Objective: To determine the T1/2 of equine cTnI.Methods: Four healthy ponies received i.v. injections of recombinant equine cTnI. Plasma cTnI concentrations were measured with a point‐of‐care cTnI analyser at multiple time points after injection. Standard pharmacokinetic analysis was performed to establish the T1/2 of cTnI.Results: The average T1/2 of cTnI was determined to be 0.47 h using a single rate elimination model.Conclusion: The elimination of recombinant equine cTnI following i.v. administration is very rapid. Establishing the T1/2 of troponin provides critical information in understanding the clinical application of this cardiac biomarker in equine practice.
Left ventricular mechanics in humans with high aerobic fitness: adaptation independent of structural remodelling, arterial haemodynamics and heart rate
Authors: Stöhr Eric J. , McDonnell Barry , Thompson Jane , Stone Keeron , Bull Tom , Houston Rory , Cockcroft John , Shave Rob 
Published: March 2012

Key points
During cardiac contraction, left ventricular (LV) mechanics play an important role in equalising transmural fibre stress and ensuring efficient ejection of blood.
The factors responsible for altered LV mechanics in humans with high aerobic exercise capacity are unknown but are believed to be related to changes in LV structure or heart rate.
We performed a comprehensive assessment of LV mechanics and cardiovascular function at rest and during dynamic exercise in individuals with moderate and high aerobic exercise capacity.
Our novel data indicate that there is no direct association between altered LV mechanics in humans with high aerobic fitness and classic indicators of cardiovascular adaptation.
The findings provide evidence of a previously unknown type of physiological LV adaptation that may have important implications for exercise training in various healthy and diseased populations.
Effects of chemostimuli on [Ca2+]i responses of rat aortic body type I cells and endogenous local neurons: comparison with carotid body cells
Authors: Piskuric Nikol A. , Nurse Colin A. 
Published: March 2012

Key points
Mammalian aortic bodies (ABs) are putative peripheral chemoreceptor cells presumed to monitor the oxygen content of arterial blood, although their direct chemosensitivity has never been previously demonstrated at the cellular level.
We used Ca2+ imaging to show for the first time that a variety of stimuli, including hypoxia, isohydric and acidic hypercapnia, and isocapnic acidosis, caused increases in cytosolic [Ca2+] in AB chemoreceptor cells.
We also showed that some local neurons, known to be uniquely associated with these AB paraganglia in situ, generated robust [Ca2+]i responses to these chemostimuli, suggesting that they may subserve a sensory function.
These results will help us better understand how AB cells sense the composition of the blood in their local environment near the heart, and how they communicate with sensory neurons to initiate homeostatic reflexes during situations of low oxygen supply, like anaemia.
Genotype and Subtype Profiling of PSI-7977 as a Nucleotide Inhibitor of Hepatitis C Virus
Authors: Lam Angela M. , Espiritu Christine , Bansal Shalini , Micolochick Steuer Holly M. , Niu Congrong , Zennou Veronique , Keilman Meg , Zhu Yuao , Lan Shuiyun , Otto Michael J. , Furman Phillip A. 
Published: March 2012

ABSTRACT

PSI-7977, a prodrug of 2′-F-2′-
C
-methyluridine monophosphate, is the purified diastereoisomer of PSI-7851 and is currently being investigated in phase 3 clinical trials for the treatment of hepatitis C. In this study, we profiled the activity of PSI-7977 and its ability to select for resistance using a number of different replicon cells. Results showed that PSI-7977 was active against genotype (GT) 1a, 1b, and 2a (strain JFH-1) replicons and chimeric replicons containing GT 2a (strain J6), 2b, and 3a NS5B polymerase. Cross-resistance studies using GT 1b replicons confirmed that the S282T change conferred resistance to PSI-7977. Subsequently, we evaluated the ability of PSI-7977 to select for resistance using GT 1a, 1b, and 2a (JFH-1) replicon cells. S282T was the common mutation selected among all three genotypes, but while it conferred resistance to PSI-7977 in GT 1a and 1b, JFH-1 GT 2a S282T showed only a very modest shift in 50% effective concentration (EC
50
) for PSI-7977. Sequence analysis of the JFH-1 NS5B region indicated that additional amino acid changes were selected both prior to and after the emergence of S282T. These include T179A, M289L, I293L, M434T, and H479P. Residues 179, 289, and 293 are located within the finger and palm domains, while 434 and 479 are located on the surface of the thumb domain. Data from the JFH-1 replicon variants showed that amino acid changes within the finger and palm domains together with S282T were required to confer resistance to PSI-7977, while the mutations on the thumb domain serve to enhance the replication capacity of the S282T replicons.
In VitroActivities of Clindamycin, Imipenem, Metronidazole, and Piperacillin-Tazobactam against Susceptible and Resistant Isolates of Bacteroides fragilis Evaluated by Kill Kinetics
Authors: Schaumann Reiner , Funke Matthias , Janssen Eva , Rodloff Arne C. 
Published: March 2012

ABSTRACTThe aim of the present study was to investigate the activities of clindamycin, imipenem, metronidazole, and piperacillin-tazobactam against 12Bacteroides fragilisisolates (resistant and susceptible strains) by kill kinetics over 24 h. In contrast to the other antimicrobial agents, clindamycin did not affect strains with MICs of >8.0 μg/ml. For those strains with MICs of ≤8.0 μg/ml, all employed antibiotics except clindamycin showed nearly bactericidal activity. Metronidazole proved to be the most active antimicrobial agent.
A Loss-of-Function Mutation in the PAS Kinase Rim15p Is Related to Defective Quiescence Entry and High Fermentation Rates of Saccharomyces cerevisiae Sake Yeast Strains
Authors: Watanabe Daisuke , Araki Yuya , Zhou Yan , Maeya Naoki , Akao Takeshi , Shimoi Hitoshi 
Published: March 2012

ABSTRACT

Sake yeast cells have defective entry into the quiescent state, allowing them to sustain high fermentation rates. To reveal the underlying mechanism, we investigated the PAS kinase Rim15p, which orchestrates initiation of the quiescence program in
Saccharomyces cerevisiae
. We found that Rim15p is truncated at the carboxyl terminus in modern sake yeast strains as a result of a frameshift mutation. Introduction of this mutation or deletion of the full-length
RIM15
gene in a laboratory strain led to a defective stress response, decreased synthesis of the storage carbohydrates trehalose and glycogen, and impaired G
1
arrest, which together closely resemble the characteristic phenotypes of sake yeast. Notably, expression of a functional
RIM15
gene in a modern sake strain suppressed all of these phenotypes, demonstrating that dysfunction of Rim15p prevents sake yeast cells from entering quiescence. Moreover, loss of Rim15p or its downstream targets Igo1p and Igo2p remarkably improved the fermentation rate in a laboratory strain. This finding verified that Rim15p-mediated entry into quiescence plays pivotal roles in the inhibition of ethanol fermentation. Taken together, our results suggest that the loss-of-function mutation in the
RIM15
gene may be the key genetic determinant of the increased ethanol production rates in modern sake yeast strains.
Comparative Analysis of Eukaryotic Marine Microbial Assemblages from 18S rRNA Gene and Gene Transcript Clone Libraries by Using Different Methods of Extraction
Authors: Koid Amy , Nelson William C. , Mraz Amy , Heidelberg Karla B. 
Published: March 2012

ABSTRACT
Eukaryotic marine microbes play pivotal roles in biogeochemical nutrient cycling and ecosystem function, but studies that focus on the protistan biogeography and genetic diversity lag-behind studies of other microbes. 18S rRNA PCR amplification and clone library sequencing are commonly used to assess diversity that is culture independent. However, molecular methods are not without potential biases and artifacts. In this study, we compare the community composition of clone libraries generated from the same water sample collected at the San Pedro Ocean Time Series (SPOTs) station in the northwest Pacific Ocean. Community composition was assessed using different cell lysis methods (chemical and mechanical) and the extraction of different nucleic acids (DNA and RNA reverse transcribed to cDNA) to build Sanger ABI clone libraries. We describe specific biases for ecologically important phylogenetic groups resulting from differences in nucleic acid extraction methods that will inform future designs of eukaryotic diversity studies, regardless of the target sequencing platform planned.
Direct Conversion of Xylan to Ethanol by Recombinant Saccharomyces cerevisiae Strains Displaying an Engineered Minihemicellulosome
Authors: Sun Jie , Wen Fei , Si Tong , Xu Jian-He , Zhao Huimin 
Published: March 2012

ABSTRACT

Arabinoxylan is a heteropolymeric chain of a β-1,4-linked xylose backbone substituted with arabinose residues, representing a principal component of plant cell walls. Here we developed recombinant
Saccharomyces cerevisiae
strains as whole-cell biocatalysts capable of combining hemicellulase production, xylan hydrolysis, and hydrolysate fermentation into a single step. These strains displayed a series of uni-, bi-, and trifunctional minihemicellulosomes that consisted of a miniscaffoldin (CipA3/CipA1) and up to three chimeric enzymes. The miniscaffoldin derived from
Clostridium thermocellum
contained one or three cohesin modules and was tethered to the cell surface through the
S. cerevisia
e a-agglutinin adhesion receptor. Up to three types of hemicellulases, an endoxylanase (XynII), an arabinofuranosidase (AbfB), and a β-xylosidase (XlnD), each bearing a C-terminal dockerin, were assembled onto the miniscaffoldin by high-affinity cohesin-dockerin interactions. Compared to uni- and bifunctional minihemicellulosomes, the resulting quaternary trifunctional complexes exhibited an enhanced rate of hydrolysis of arabinoxylan. Furthermore, with an integrated
d
-xylose-utilizing pathway, the recombinant yeast displaying the bifunctional minihemicellulosome CipA3-XynII-XlnD could simultaneously hydrolyze and ferment birchwood xylan to ethanol with a yield of 0.31 g per g of sugar consumed.
Role of Extracellular Transaldolase from Bifidobacterium bifidum in Mucin Adhesion and Aggregation
Authors: González-Rodríguez Irene , Sánchez Borja , Ruiz Lorena , Turroni Francesca , Ventura Marco , Ruas-Madiedo Patricia , Gueimonde Miguel , Margolles Abelardo 
Published: March 2012

ABSTRACT

The ability of bifidobacteria to establish in the intestine of mammals is among the main factors considered to be important for achieving probiotic effects. The role of surface molecules from
Bifidobacterium bifidum
taxon in mucin adhesion capability and the aggregation phenotype of this bacterial species was analyzed. Adhesion to the human intestinal cell line HT29 was determined for a collection of 12
B. bifidum
strains. In four of them—
B. bifidum
LMG13195, DSM20456, DSM20239, and A8—the involvement of surface-exposed macromolecules in the aggregation phenomenon was determined. The aggregation of
B. bifidum
A8 and DSM20456 was abolished after treatment with proteinase K, this effect being more pronounced for the strain A8. Furthermore, a mucin binding assay of
B. bifidum
A8 surface proteins showed a high adhesive capability for its transaldolase (Tal). The localization of this enzyme on the surface of
B. bifidum
A8 was unequivocally demonstrated by immunogold electron microscopy experiments. The gene encoding Tal from
B. bifidum
A8 was expressed in
Lactococcus lactis
, and the protein was purified to homogeneity. The pure protein was able to restore the autoaggregation phenotype of proteinase K-treated
B. bifidum
A8 cells. A recombinant
L. lactis
strain, engineered to secrete Tal, displayed a mucin- binding level more than three times higher than the strain not producing the transaldolase. These findings suggest that Tal, when exposed on the cell surface of
B. bifidum
, could act as an important colonization factor favoring its establishment in the gut.
The Recall Response Induced by Genital Challenge with Chlamydia muridarum Protects the Oviduct from Pathology but Not from Reinfection
Authors: Riley Melissa M. , Zurenski Matthew A. , Frazer Lauren C. , O'Connell Catherine M. , Andrews Charles W. , Mintus Margaret , Darville Toni 
Published: March 2012

ABSTRACT

The significant morbidities of ectopic pregnancy and infertility observed in women after
Chlamydia trachomatis
genital infection result from ascension of the bacteria from the endocervix to the oviduct, where an overly aggressive inflammatory response leads to chronic scarring and Fallopian tube obstruction. A vaccine to prevent chlamydia-induced disease is urgently needed. An important question for vaccine development is whether sterilizing immunity at the level of the oviduct is essential for protection because of the possibility that a chlamydial component drives a deleterious anamnestic T cell response upon oviduct reinfection. We show that mice inoculated with attenuated plasmid-cured strains of
Chlamydia muridarum
are protected from oviduct pathology upon challenge with wild-type
C. muridarum
Nigg despite induction of a response that did not prevent reinfection of the oviduct. Interestingly, repeated abbreviated infections with Nigg also elicited recall responses that protected the oviduct from pathology despite low-level reinfection of this vulnerable tissue site. Challenged mice displayed significant decreases in tissue infiltration of inflammatory leukocytes with marked reductions in frequencies of neutrophils but significant increases in frequencies of CD4 Th1 and CD8 T cells. An anamnestic antibody response was also detected. These data indicate that exposure to a live attenuated chlamydial vaccine or repeated abbreviated genital infection with virulent chlamydiae promotes anamnestic antibody and T cell responses that protect the oviduct from pathology despite a lack of sterilizing immunity at the site.
Visualization of an Alphaherpesvirus Membrane Protein That Is Essential for Anterograde Axonal Spread of Infection in Neurons
Authors: Taylor M. P. , Kramer T. , Lyman M. G. , Kratchmarov R. , Enquist L. W. 
Published: March 2012

ABSTRACT
Pseudorabies virus (PRV), an alphaherpesvirus with a broad host range, replicates and spreads in chains of synaptically connected neurons. The PRV protein Us9 is a small membrane protein that is highly conserved among alphaherpesviruses and is essential for anterograde axonal spread in neurons. Specifically, the Us9 protein is required for the sorting of newly assembled PRV particles into axons. However, the molecular details underlying the function of Us9 are poorly understood. Here we constructed PRV strains that express functional green fluorescent protein (GFP)-Us9 fusion proteins in order to visualize axonal transport of viral particles in infected rat superior cervical ganglion neurons. We show that GFP-Us9-labeled structures are transported exclusively in the anterograde direction within axons. Additionally, the vast majority of anterograde-directed capsids (labeled with VP26-monomeric red fluorescent protein) and a viral membrane protein (labeled with glycoprotein M fused to mCherry) are cotransported with GFP-Us9 in the anterograde direction. In contrast, during infection with PRV strains that express nonfunctional mutant GFP-Us9 proteins, cotransport of mutant GFP-Us9 with capsids in axons is abolished. These findings show that axonal sorting of progeny viral particles is dependent upon the association of viral structures with membranes that contain functional Us9 proteins. This association is required for anterograde spread of infection in neurons.

IMPORTANCE
Alphaherpesviruses, such as pseudorabies virus (PRV), are parasites of the mammalian nervous system. These viruses spread over long distances in chains of synaptically connected neurons. PRV encodes several proteins that mediate directed virion transport and spread of infection. Us9 is a highly conserved viral membrane protein that is essential for anterograde neuronal spread of infection. In the absence of Us9, newly replicated viral particles are assembled in the cell body but are not sorted into or transported within axons. Here, we constructed and characterized novel PRV strains that express functional green fluorescent protein (GFP)-Us9 fusion proteins in order to visualize its localization in living neurons during infection. This enabled us to better understand the function of Us9 in facilitating the spread of infection. We show that all viral particles moving in the anterograde direction are labeled with GFP-Us9, suggesting that the presence of Us9 determines the capacity for directed transport within axons.