bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple functionally divergent and conserved copies of alpha tubulin in bdelloid rotifers
Authors: Eyres Isobel , Frangedakis Eftychios , Fontaneto Diego , Herniou Elisabeth A , Boschetti Chiara , Carr Adrian , Micklem Gos , Tunnacliffe Alan , Barraclough Timothy G 
Published: August 2012

Abstract

Background
Bdelloid rotifers are microscopic animals that have apparently survived without sex for millions of years and are able to survive desiccation at all life stages through a process called anhydrobiosis. Both of these characteristics are believed to have played a role in shaping several unusual features of bdelloid genomes discovered in recent years. Studies into the impact of asexuality and anhydrobiosis on bdelloid genomes have focused on understanding gene copy number. Here we investigate copy number and sequence divergence in alpha tubulin. Alpha tubulin is conserved and normally present in low copy numbers in animals, but multiplication of alpha tubulin copies has occurred in animals adapted to extreme environments, such as cold-adapted Antarctic fish. Using cloning and sequencing we compared alpha tubulin copy variation in four species of bdelloid rotifers and four species of monogonont rotifers, which are facultatively sexual and cannot survive desiccation as adults. Results were verified using transcriptome data from one bdelloid species, Adineta ricciae.

Results
In common with the typical pattern for animals, monogonont rotifers contain either one or two copies of alpha tubulin, but bdelloid species contain between 11 and 13 different copies, distributed across five classes. Approximately half of the copies form a highly conserved group that vary by only 1.1% amino acid pairwise divergence with each other and with the monogonont copies. The other copies have divergent amino acid sequences that evolved significantly faster between classes than within them, relative to synonymous changes, and vary in predicted biochemical properties. Copies of each class were expressed under the laboratory conditions used to construct the transcriptome.

Conclusions
Our findings are consistent with recent evidence that bdelloids are degenerate tetraploids and that functional divergence of ancestral copies of genes has occurred, but show how further duplication events in the ancestor of bdelloids led to proliferation in both conserved and functionally divergent copies of this gene.
Failure of delayed nonsynaptic neuronal plasticity underlies age-associated long-term associative memory impairment
Authors: Watson Shawn N , Risling Tara E , Hermann Petra M , Wildering Willem C 
Published: August 2012

AbstractBackgroundCognitive impairment associated with subtle changes in neuron and neuronal network function rather than widespread neuron death is a feature of the normal aging process in humans and animals. Despite its broad evolutionary conservation, the etiology of this aging process is not well understood. However, recent evidence suggests the existence of a link between oxidative stress in the form of progressive membrane lipid peroxidation, declining neuronal electrical excitability and functional decline of the normal aging brain. The current study applies a combination of behavioural and electrophysiological techniques and pharmacological interventions to explore this hypothesis in a gastropod model (Lymnaea stagnalisfeeding system) that allows pinpointing the molecular and neurobiological foundations of age-associated long-term memory (LTM) failure at the level of individual identified neurons and synapses.ResultsClassical appetitive reward-conditioning induced robust LTM in mature animals in the first quartile of their lifespan but failed to do so in animals in the last quartile of their lifespan. LTM failure correlated with reduced electrical excitability of two identified serotonergic modulatory interneurons (CGCs) critical in chemosensory integration by the neural network controlling feeding behaviour. Moreover, while behavioural conditioning induced delayed-onset persistent depolarization of the CGCs known to underlie appetitive LTM formation in this model in the younger animals, it failed to do so in LTM-deficient senescent animals. Dietary supplementation of the lipophilic anti-oxidant α-tocopherol reversed the effect of age on CGCs electrophysiological characteristics but failed to restore appetitive LTM function. Treatment with the SSRI fluoxetine reversed both the neurophysiological and behavioural effects of age insenioranimals.ConclusionsThe results identify the CGCs as cellular loci of age-associated appetitive learning and memory impairment inLymnaeaand buttress the hypothesis that lipid peroxidation-dependent depression of intrinsic excitability is a hallmark of normal neuronal aging. The data implicate both lipid peroxidation-dependent non-synaptic as well as apparently lipid peroxidation-independent synaptic mechanisms in the age-dependent decline in behavioural plasticity in this model system.
Differential effects of the changes of LDL cholesterol and systolic blood pressure on the risk of carotid artery atherosclerosis
Authors: Chien Kuo-Liong , Tu Yu-Kang , Hsu Hsiu-Ching , Su Ta-Chen , Lin Hung-Ju , Chen Ming-Fong , Lee Yuan-Teh 
Published: August 2012

Abstract

Background
The effects of baseline and changes in blood pressure and low density lipoprotein (LDL) cholesterol on the carotid intima media thickness (IMT) have not been well documented.

Methods
A total of 2572 adults (mean age 53.8 years, 54.6% women) in a Taiwanese community undertook three blood pressure and LDL cholesterol examinations over 6 years. Latent growth curve modeling was used to investigate the effects of baseline and change in blood pressure and LDL cholesterol on IMT.

Results
Greater baseline LDL and blood pressure were associated with an increase in IMT (0.005 ± 0.002 mm per 1 mg/dL [p = 0.006] and 0.041 ± 0.004 mm mmHg [p <0.0001], respectively. Change in blood pressure was associated with a significant increase in IMT (0.047±0.016, P = 0.004), whilst the association between change in LDL and change in IMT was not statistically significant (0.008±0.006, P = 0.20).

Conclusions
Carotid IMT was associated with baseline blood pressure and LDL cholesterol, yet only changes of blood pressure, not LDL cholesterol, were related to carotid IMT during the 6-year observation.
The effect of hospital volume on patient outcomes in severe acute pancreatitis
Authors: Shen Hsiu-Nien , Lu Chin-Li , Li Chung-Yi 
Published: August 2012

Abstract

Background
We investigated the relation between hospital volume and outcome in patients with severe acute pancreatitis (SAP). The determination is important because patient outcome may be improved through volume-based selective referral.

Methods
In this cohort study, we analyzed 22,551 SAP patients in 2,208 hospital-years (between 2000 and 2009) from Taiwan’s National Health Insurance Research Database. Primary outcome was hospital mortality. Secondary outcomes were hospital length of stay and charges. Hospital SAP volume was measured both as categorical and as continuous variables (per one case increase each hospital-year). The effect was assessed using multivariable logistic regression models with generalized estimating equations accounting for hospital clustering effect. Adjusted covariates included patient and hospital characteristics (model 1), and additional treatment variables (model 2).

Results
Irrespective of the measurements, increasing hospital volume was associated with reduced risk of hospital mortality after adjusting the patient and hospital characteristics (adjusted odds ratio [OR] 0.995, 95% confidence interval [CI] 0.993-0.998 for per one case increase). The patients treated in the highest volume quartile (≥14 cases per hospital-year) had 42% lower risk of hospital mortality than those in the lowest volume quartile (1 case per hospital-year) after adjusting the patient and hospital characteristics (adjusted OR 0.58, 95% CI 0.40-0.83). However, an inverse relation between volume and hospital stay or hospital charges was observed only when the volume was analyzed as a categorical variable. After adjusting the treatment covariates, the volume effect on hospital mortality disappeared regardless of the volume measures.

Conclusions
These findings support the use of volume-based selective referral for patients with SAP and suggest that differences in levels or processes of care among hospitals may have contributed to the volume effect.
Neutrophil necrosis and annexin 1 degradation associated with airway inflammation in lung transplant recipients with cystic fibrosis
Authors: Tsao Francis H C , Xiang Zhuzai , Abbasi Adnan , Meyer Keith C 
Published: August 2012

AbstractBackgroundNeutrophils sequestered in lower respiratory tract secretions in the inflamed lung may undergo apoptosis and/or necrosis and release toxic cellular contents that can injure airways or parenchyma. This study examined the viability of neutrophils retrieved from the proximal airways of lung transplant recipients with bacterial tracheobronchitis.MethodsIntegrity and stability of intracellular proteins in neutrophils from proximal airways and peripheral blood from lung transplant recipients with bacterial tracheobronchitis were analyzed via Western blot analysis and determination of neutrophil viability by morphologic appearance and flow cytometry.ResultsNeutrophils in tracheobronchial secretions from lung transplant recipients with cystic fibrosis who had normal chest radiographic imaging but bronchoscopic evidence of purulent tracheobronchitis post-transplant were necrotic and associated with degradation of intracellular protein annexin 1. The neutrophil influx was compartmentalized to large airways and not detected in peripheral bronchoalveolar airspaces sampled via bronchoalveolar lavage. Peripheral blood neutrophils from healthy subjects culturedin vitrodemonstrated that annexin 1 degradation, particularly to a 33 kDa annexin 1 breakdown product (A1-BP), was associated with neutrophil necrosis, but not apoptosis. Although annexin 1 degradation was not specific to neutrophil necrosis, it was a sensitive marker of intracellular protein degradation associated with neutrophil necrosis. Annexin 1 degradation to 33 kDa A1-BP was not observed in peripheral blood neutrophils from healthy subjects, but annexin 1 appeared to be degraded in peripheral blood neutrophils of lung transplant recipients despite a normal morphologic appearance of these cells.ConclusionsNeutrophils were necrotic from the proximal airways of lung transplant recipients with bacterial tracheobronchitis, and this process may begin when neutrophils are still in the systemic circulation prior to sequestration in inflamed airways. Annexin 1 degradation to 33 kDa A1-BP may be useful as a sensitive marker to detect neutrophil necrosis.
Oncolytic vaccinia virus GLV-1h68 strain shows enhanced replication in human breast cancer stem-like cells in comparison to breast cancer cells
Authors: Wang Huiqiang , Chen Nanhai G , Minev Boris R , Szalay Aladar A 
Published: August 2012

AbstractBackgroundRecent data suggest that cancer stem cells (CSCs) play an important role in cancer, as these cells possess enhanced tumor-forming capabilities and are responsible for relapses after apparently curative therapies have been undertaken. Hence, novel cancer therapies will be needed to test for both tumor regression and CSC targeting. The use of oncolytic vaccinia virus (VACV) represents an attractive anti-tumor approach and is currently under evaluation in clinical trials. The purpose of this study was to demonstrate whether VACV does kill CSCs that are resistant to irradiation and chemotherapy.MethodsCancer stem-like cells were identified and separated from the human breast cancer cell line GI-101A by virtue of increased aldehyde dehydrogenase 1 (ALDH1) activity as assessed by the ALDEFLUOR assay and cancer stem cell-like features such as chemo-resistance, irradiation-resistance and tumor-initiating were confirmed in cell culture and in animal models. VACV treatments were applied to both ALDEFLUOR-positive cells in cell culture and in xenograft tumors derived from these cells. Moreover, we identified and isolated CD44+CD24+ESA+cells from GI-101A upon an epithelial-mesenchymal transition (EMT). These cells were similarly characterized both in cell culture and in animal models.ResultsWe demonstrated for the first time that the oncolytic VACV GLV-1h68 strain replicated more efficiently in cells with higher ALDH1 activity that possessed stem cell-like features than in cells with lower ALDH1 activity. GLV-1h68 selectively colonized and eventually eradicated xenograft tumors originating from cells with higher ALDH1 activity. Furthermore, GLV-1h68 also showed preferential replication in CD44+CD24+ESA+cells derived from GI-101A upon an EMT induction as well as in xenograft tumors originating from these cells that were more tumorigenic than CD44+CD24-ESA+cells.ConclusionsTaken together, our findings indicate that GLV-1h68 efficiently replicates and kills cancer stem-like cells. Thus, GLV-1h68 may become a promising agent for eradicating both primary and metastatic tumors, especially tumors harboring cancer stem-like cells that are resistant to chemo and/or radiotherapy and may be responsible for recurrence of tumors.
Genetic, environmental and stochastic factors in monozygotic twin discordance with a focus on epigenetic differences
Authors: Czyz Witold , Morahan Julia M , Ebers George C , Ramagopalan Sreeram V 
Published: August 2012

AbstractGenetic-epidemiological studies on monozygotic (MZ) twins have been used for decades to tease out the relative contributions of genes and the environment to a trait. Phenotypic discordance in MZ twins has traditionally been ascribed to non-shared environmental factors acting after birth, however recent data indicate that this explanation is far too simple. In this paper, we review other reasons for discordance, including differences in thein uteroenvironment, genetic mosaicism, and stochastic factors, focusing particularly on epigenetic discordance. Epigenetic differences are gaining increasing recognition. Although it is clear that in specific cases epigenetic alterations provide a causal factor in disease etiology, the overall significance of epigenetics in twin discordance remains unclear. It is also challenging to determine the causality and relative contributions of environmental, genetic, and stochastic factors to epigenetic variability. Epigenomic profiling studies have recently shed more light on the dynamics of temporal methylation change and methylome heritability, yet have not given a definite answer regarding their relevance to disease, because of limitations in establishing causality. Here, we explore the subject of epigenetics as another component in human phenotypic variability and its links to disease focusing particularly on evidence from MZ twin studies.
High throughput phenotyping for aphid resistance in large plant collections
Authors: Chen Xi , Vosman Ben , Visser Richard GF , van der Vlugt René AA , Broekgaarden Colette 
Published: August 2012

Abstract

Background
Phloem-feeding insects are among the most devastating pests worldwide. They not only cause damage by feeding from the phloem, thereby depleting the plant from photo-assimilates, but also by vectoring viruses. Until now, the main way to prevent such problems is the frequent use of insecticides. Applying resistant varieties would be a more environmental friendly and sustainable solution. For this, resistant sources need to be identified first. Up to now there were no methods suitable for high throughput phenotyping of plant germplasm to identify sources of resistance towards phloem-feeding insects.

Results
In this paper we present a high throughput screening system to identify plants with an increased resistance against aphids. Its versatility is demonstrated using an Arabidopsis thaliana activation tag mutant line collection. This system consists of the green peach aphid Myzus persicae (Sulzer) and the circulative virus Turnip yellows virus (TuYV). In an initial screening, with one plant representing one mutant line, 13 virus-free mutant lines were identified by ELISA. Using seeds produced from these lines, the putative candidates were re-evaluated and characterized, resulting in nine lines with increased resistance towards the aphid.

Conclusions
This M. persicae-TuYV screening system is an efficient, reliable and quick procedure to identify among thousands of mutated lines those resistant to aphids. In our study, nine mutant lines with increased resistance against the aphid were selected among 5160 mutant lines in just 5 months by one person. The system can be extended to other phloem-feeding insects and circulative viruses to identify insect resistant sources from several collections, including for example genebanks and artificially prepared mutant collections.
Construction of a recombinant eukaryotic expression vector containing PHD3 gene and its expression in HepG2 cells
Authors: Liang Qi-Lian , Li Zhou-Yu , Zhou Yuan , Liu Qiu-Long , Ou Wen-Ting , Huang Zhi-Gang 
Published: August 2012

Abstract
Prolyl hydroxylase domain 3 (PHD3) is a hypoxia inducible factor-α (HIFα) regulator; it degrades HIFα in the presence of oxygen. Recently, there have been an increasing number of studies about the role of PHD3 in proliferation and apoptosis of cancer cells. However, most of the evidence for the role of PHD3 is observational, and little is known of the molecular mechanism. In our current study, we constructed a recombinant eukaryotic expression vector containing the PHD3 gene and detected its biological activity in human hepatoma cell line (HepG2 cells). We successfully constructed a recombinant pcDNA 3.1(+)-PHD3 plasmid; the results showed that PHD3 overexpression could inhibit the proliferation of HepG2 cells and induce apoptosis by activating caspase-3 activity. Our study has provided preliminary materials and data for further investigation of the effect of PHD3 on HepG2 cells.
Production of 1,3-PDO and butanol by a mutant strain of Clostridium pasteurianum with increased tolerance towards crude glycerol
Authors: Jensen Torbjørn Ølshøj , Kvist Thomas , Mikkelsen Marie Just , Westermann Peter 
Published: August 2012

Abstract
The production of biodiesel results in a concomitant production of crude glycerol (10% w/w). Clostridium pasteurianum can utilize glycerol as sole carbon source and converts it into 1,3-propanediol, ethanol, butanol, and CO2. Reduced growth and productivities on crude glycerol as compared to technical grade glycerol have previously been observed. In this study, we applied random mutagenesis mediated by ethane methyl sulfonate (EMS) to develop a mutant strain of C. pasteurianum tolerating high concentrations of crude glycerol. At an initial crude glycerol concentration of 25 g/l the amount of dry cell mass produced by the mutant strain was six times higher than the amount produced by the wild type. Growth of the mutant strain was even detected at an initial crude glycerol concentration of 105 g/l. A pH controlled reactor with in situ removal of butanol by gas-stripping was used to evaluate the performance of the mutant strain. Utilizing stored crude glycerol, the mutant strain showed significantly increased rates compared to the wild type. A maximum glycerol utilization rate of 7.59 g/l/h was observed along with productivities of 1.80 g/l/h and 1.21 g/l/h of butanol and 1,3-PDO, respectively. These rates are higher than what previously has been published for C. pasteurianum growing on technical grade glycerol in fed batch reactors. In addition, high yields of the main products (butanol and 1,3-PDO) were detected and these two products were efficiently separated in two steams using gas-stripping.
Fractional clearance of urate: validation of measurement in spot-urine samples in healthy subjects and gouty patients
Authors: Kannangara Diluk RW , Ramasamy Sheena N , Indraratna Praveen L , Stocker Sophie L , Graham Garry G , Jones Graham , Portek Ian , Williams Kenneth M , Day Richard O 
Published: August 2012

Abstract
Introduction
Hyperuricemia is the greatest risk factor for gout and is caused by an overproduction and/or inefficient renal clearance of urate. The fractional renal clearance of urate (FCU, renal clearance of urate/renal clearance of creatinine) has been proposed as a tool to identify subjects who manifest inefficient clearance of urate. The aim of the present studies was to validate the measurement of FCU by using spot-urine samples as a reliable indicator of the efficiency of the kidney to remove urate and to explore its distribution in healthy subjects and gouty patients.

Methods
Timed (spot, 2-hour, 4-hour, 6-hour, 12-hour, and 24-hour) urine collections were used to derive FCU in 12 healthy subjects. FCUs from spot-urine samples were then determined in 13 healthy subjects twice a day, repeated on 3 nonconsecutive days. The effect of allopurinol, probenecid, and the combination on FCU was explored in 11 healthy subjects. FCU was determined in 36 patients with gout being treated with allopurinol. The distribution of FCU was examined in 118 healthy subjects and compared with that from the 36 patients with gout.

Results
No substantive or statistically significant differences were observed between the FCUs derived from spot and 24-hour urine collections. Coefficients of variation (CVs) were both 28%. No significant variation in the spot FCU was obtained either within or between days, with mean intrasubject CV of 16.4%. FCU increased with probenecid (P < 0.05), whereas allopurinol did not change the FCU in healthy or gouty subjects. FCUs of patients with gout were lower than the FCUs of healthy subjects (4.8% versus 6.9%; P < 0.0001).

Conclusions
The present studies indicate that the spot-FCU is a convenient, valid, and reliable indicator of the efficiency of the kidney in removing urate from the blood and thus from tissues. Spot-FCU determinations may provide useful correlates in studies investigating molecular mechanisms underpinning the observed range of efficiencies of the kidneys in clearing urate from the blood.

Trial Registration
ACTRN12611000743965
Magnitude of stimulation dictates the cannabinoid-mediated differential T cell response to HIVgp120
Authors: Chen Weimin , Kaplan Barbara L F , Pike Schuyler T , Topper Lauren A , Lichorobiec Nicholas R , Simmons Steven O , Ramabhadran Ram , Kaminski Norbert E 
Published: August 2012

Abstract
Cannabinoids differentially modulate T cell function with concomitant dysregulation of the NFAT-calcium signaling cascade.
Approximately 25% of immunocompromised HIV patients smoke marijuana for its putative therapeutic benefit. The goal of these studies was to test the hypothesis that marijuana-derived cannabinoids have immunomodulatory effects on HIV antigen-specific T cell effector function. A surrogate mouse model to induce polyclonal T cell responses against HIVgp120 was established. THC, a marijuana-derived cannabinoid, suppressed or enhanced mouse CD8+ T cell proliferation and the gp120-specific CTL response depending on the magnitude of the IFN-γ response. To determine the molecular mechanisms by which cannabinoids differentially modulate T cell responses, P/I or anti-CD3/CD28 antibodies were used for stimulation, and another marijuana-derived cannabinoid, CBD, was also investigated. THC or CBD suppressed or enhanced IFN-γ and IL-2 production by mouse splenocytes under optimal or suboptimal stimulation, respectively. Similar differential effects of cannabinoids on cytokine production were also observed on nuclear translocation of NFAT and with human PBMCs in response to P/I stimulation. However, THC and CBD elevated intracellular calcium, regardless of the stimulation level with P/I, suggesting that the cannabinoid-induced calcium increase provides an appropriate signal for activation in suboptimally stimulated T cells but an anergic-like signal as a result of excessive calcium in optimally stimulated T cells. Overall, these data demonstrate differential modulation by cannabinoids of a HIV antigen-specific response and identify a possible mechanism responsible for this effect.