bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone variant innovation in a rapidly evolving chordate lineage
Authors: Moosmann Alexandra , Campsteijn Coen , Jansen Pascal WTC , Nasrallah Carole , Raasholm Martina , Stunnenberg Henk G , Thompson Eric M 
Published: July 2011

Abstract

Background
Histone variants alter the composition of nucleosomes and play crucial roles in transcription, chromosome segregation, DNA repair, and sperm compaction. Modification of metazoan histone variant lineages occurs on a background of genome architecture that shows global similarities from sponges to vertebrates, but the urochordate, Oikopleura dioica, a member of the sister group to vertebrates, exhibits profound modification of this ancestral architecture.

Results
We show that a histone complement of 47 gene loci encodes 31 histone variants, grouped in distinct sets of developmental expression profiles throughout the life cycle. A particularly diverse array of 15 male-specific histone variants was uncovered, including a testes-specific H4t, the first metazoan H4 sequence variant reported. Universal histone variants H3.3, CenH3, and H2A.Z are present but O. dioica lacks homologs of macroH2A and H2AX. The genome encodes many H2A and H2B variants and the repertoire of H2A.Z isoforms is expanded through alternative splicing, incrementally regulating the number of acetylatable lysine residues in the functionally important N-terminal "charge patch". Mass spectrometry identified 40 acetylation, methylation and ubiquitylation posttranslational modifications (PTMs) and showed that hallmark PTMs of "active" and "repressive" chromatin were present in O. dioica. No obvious reduction in silent heterochromatic marks was observed despite high gene density in this extraordinarily compacted chordate genome.

Conclusions
These results show that histone gene complements and their organization differ considerably even over modest phylogenetic distances. Substantial innovation among all core and linker histone variants has evolved in concert with adaptation of specific life history traits in this rapidly evolving chordate lineage.
The MEK-ERK pathway negatively regulates bim expression through the 3' UTR in sympathetic neurons
Authors: Hughes Rosie , Gilley Jonathan , Kristiansen Mark , Ham Jonathan 
Published: July 2011

Abstract

Background
Apoptosis plays a critical role during neuronal development and disease. Developing sympathetic neurons depend on nerve growth factor (NGF) for survival during the late embryonic and early postnatal period and die by apoptosis in its absence. The proapoptotic BH3-only protein Bim increases in level after NGF withdrawal and is required for NGF withdrawal-induced death. The regulation of Bim expression in neurons is complex and this study describes a new mechanism by which an NGF-activated signalling pathway regulates bim gene expression in sympathetic neurons.

Results
We report that U0126, an inhibitor of the prosurvival MEK-ERK pathway, increases bim mRNA levels in sympathetic neurons in the presence of NGF. We find that this effect is independent of PI3-K-Akt and JNK-c-Jun signalling and is not mediated by the promoter, first exon or first intron of the bim gene. By performing 3' RACE and microinjection experiments with a new bim-LUC+3'UTR reporter construct, we show that U0126 increases bim expression via the bim 3' UTR. We demonstrate that this effect does not involve a change in bim mRNA stability and by using PD184352, a specific MEK1/2-ERK1/2 inhibitor, we show that this mechanism involves the MEK1/2-ERK1/2 pathway. Finally, we demonstrate that inhibition of MEK/ERK signalling independently reduces cell survival in NGF-treated sympathetic neurons.

Conclusions
These results suggest that in sympathetic neurons, MEK-ERK signalling negatively regulates bim expression via the 3' UTR and that this regulation is likely to be at the level of transcription. This data provides further insight into the different mechanisms by which survival signalling pathways regulate bim expression in neurons.
Adenylyl Cyclase type 3, a marker of primary cilia, is reduced in primary cell culture and in lumbar spinal cord in situ in G93A SOD1 mice
Authors: Ma Xiaoxing , Peterson Randy , Turnbull John 
Published: July 2011

AbstractBackgroundThe primary cilium is a solitary organelle important in cellular signaling, that projects from the cell surface of most growth-arrested or post-mitotic cells including neurons in the central nervous system. We hypothesized that primary cilial dysfunction might play a role in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS), and as a first step, report on the prevalence of primary cilial markers on cultured motor neurons from the lumbar spinal cord of embryonic wildtype (WT) and transgenic G93A SOD1 mice, and on motor neurons in situ in the lumbar spinal cord.ResultsAt 7 days in culture there is no difference in the proportion of G93A SOD1 and WT motor neurons staining for the cilial marker ACIII. However, at 21 days there is a large relative drop in the proportion of ciliated G93A SOD1 motor neurons. In situ, at 40 days there was a slight relative drop in the proportion of ciliated motor neurons in G93A SOD1 mice. At 98 days of age there was no change in motor neuron ciliation in WT mice, but there was motor neuron loss and a large reduction in the proportion of surviving motor neurons bearing a primary cilium in G93A SOD1 mice.ConclusionsIn primary culture and in situ in G93A SOD1 mice there is a large reduction in the proportion of motor neurons bearing a primary cilium.
Paracetamol in therapeutic dosages and acute liver injury: causality assessment in a prospective case series
Authors: Sabaté Mònica , Ibáñez Luisa , Pérez Eulàlia , Vidal Xavier , Buti Maria , Xiol Xavier , Mas Antoni , Guarner Carlos , Forné Montserrat , Solà Ricard , Castellote José , Rigau Joaquim , Laporte Joan-Ramon 
Published: July 2011

Abstract

Background
Acute liver injury (ALI) induced by paracetamol overdose is a well known cause of emergency hospital admission and death. However, there is debate regarding the risk of ALI after therapeutic dosages of the drug.
The aim is to describe the characteristics of patients admitted to hospital with jaundice who had previous exposure to therapeutic doses of paracetamol. An assessment of the causality role of paracetamol was performed in each case.

Methods
Based on the evaluation of prospectively gathered cases of ALI with detailed clinical information, thirty-two cases of ALI in non-alcoholic patients exposed to therapeutic doses of paracetamol were identified. Two authors assessed all drug exposures by using the CIOMS/RUCAM scale. Each case was classified into one of five categories based on the causality score for paracetamol.

Results
In four cases the role of paracetamol was judged to be unrelated, in two unlikely, and these were excluded from evaluation. In seven of the remaining 26 cases, the RUCAM score associated with paracetamol was higher than that associated with other concomitant medications. The estimated incidence of ALI related to the use of paracetamol in therapeutic dosages was 0.4 per million inhabitants older than 15 years of age and per year (99%CI, 0.2-0.8) and of 10 per million paracetamol users-year (95% CI 4.3-19.4).

Conclusions
Our results indicate that paracetamol in therapeutic dosages may be considered in the causality assessment in non-alcoholic patients with liver injury, even if the estimated incidence of ALI related to paracetamol appears to be low.
Tenascin-C induces inflammatory mediators and matrix degradation in osteoarthritic cartilage
Authors: Patel Lisha , Sun Weiyong , Glasson Sonya S , Morris Elisabeth A , Flannery Carl R , Chockalingam Priya S 
Published: July 2011

Abstract

Background
Tenascin-C (TN-C) is an extracellular matrix glycoprotein that is involved in tissue injury and repair processes. We analyzed TN-C expression in normal and osteoarthritic (OA) human cartilage, and evaluated its capacity to induce inflammatory and catabolic mediators in chondrocytes in vitro. The effect of TN-C on proteoglycan loss from articular cartilage in culture was also assessed.

Methods
TN-C in culture media, cartilage extracts, and synovial fluid of human and animal joints was quantified using a sandwich ELISA and/or analyzed by Western immunoblotting. mRNA expression of TN-C and aggrecanases were analyzed by Taqman assays. Human and bovine primary chondrocytes and/or explant culture systems were utilized to study TN-C induced inflammatory or catabolic mediators and proteoglycan loss. Total proteoglycan and aggrecanase -generated ARG-aggrecan fragments were quantified in human and rat synovial fluids by ELISA.

Results
TN-C protein and mRNA expression were significantly upregulated in OA cartilage with a concomitant elevation of TN-C levels in the synovial fluid of OA patients. IL-1 enhanced TN-C expression in articular cartilage. Addition of TN-C induced IL-6, PGE2, and nitrate release and upregulated ADAMTS4 mRNA in cultured primary human and bovine chondrocytes. TN-C treatment resulted in an increased loss of proteoglycan from cartilage explants in culture. A correlation was observed between TN-C and aggrecanase generated ARG-aggrecan fragment levels in the synovial fluid of human OA joints and in the lavage of rat joints that underwent surgical induction of OA.

Conclusions
TN-C expression in the knee cartilage and TN-C levels measured in the synovial fluid are significantly enhanced in OA patients. Our findings suggest that the elevated levels of TN-C could induce inflammatory mediators and promote matrix degradation in OA joints.
Identification and characterization of a new true lipase isolated through metagenomic approach
Authors: Glogauer Arnaldo , Martini Viviane P , Faoro Helisson , Couto Gustavo H , Müller-Santos Marcelo , Monteiro Rose A , Mitchell David A , de Souza Emanuel M , Pedrosa Fabio O , Krieger Nadia 
Published: July 2011

Abstract

Background
Metagenomics, the application of molecular genomics to consortia of non-cultivated microbes, has the potential to have a substantial impact on the search for novel industrial enzymes such as esterases (carboxyl ester hydrolases, EC 3.1.1.1) and lipases (triacylglycerol lipases, EC 3.1.1.3). In the current work, a novel lipase gene was identified from a fosmid metagenomic library constructed with the "prokaryotic-enriched" DNA from a fat-contaminated soil collected from a wastewater treatment plant.

Results
In preliminary screening on agar containing 1% tributyrin, 2661 of the approximately 500,000 clones in the metagenomic library showed activity. Of these, 127 showed activity on agar containing 1% tricaprylin, while 32 were shown to be true lipase producers through screening on agar containing 1% triolein. The clone with the largest halo was further characterized. Its lipase gene showed 72% identity to a putative lipase of Yersinia enterocolitica subsp. palearctica Y11. The lipase, named LipC12, belongs to family I.1 of bacterial lipases, has a chaperone-independent folding, does not possess disulfide bridges and is calcium ion dependent. It is stable from pH 6 to 11 and has activity from pH 4.5 to 10, with higher activities at alkaline pH values. LipC12 is stable up to 3.7 M NaCl and from 20 to 50°C, with maximum activity at 30°C over a 1 h incubation. The pure enzyme has specific activities of 1722 U/mg and 1767 U/mg against olive oil and pig fat, respectively. Moreover, it is highly stable in organic solvents at 15% and 30% (v/v).

Conclusions
The combination of the use of a fat-contaminated soil, enrichment of prokaryotic DNA and a three-step screening strategy led to a high number of lipase-producing clones in the metagenomic library. The most notable properties of the new lipase that was isolated and characterized were a high specific activity against long chain triacylglycerols, activity and stability over a wide range of pH values, good thermal stability and stability in water-miscible organic solvents and at high salt concentrations. These characteristics suggest that this lipase has potential to perform well in biocatalytic processes, such as for hydrolysis and synthesis reactions involving long-chain triacylglycerols and fatty acid esters.
Human-Phosphate-Binding-Protein inhibits HIV-1 gene transcription and replication
Authors: Cherrier Thomas , Elias Mikael , Jeudy Alicia , Gotthard Guillaume , Le Douce Valentin , Hallay Houda , Masson Patrick , Janossy Andrea , Candolfi Ermanno , Rohr Olivier , Chabrière Eric , Schwartz Christian 
Published: July 2011

Abstract
The Human Phosphate-Binding protein (HPBP) is a serendipitously discovered lipoprotein that binds phosphate with high affinity. HPBP belongs to the DING protein family, involved in various biological processes like cell cycle regulation. We report that HPBP inhibits HIV-1 gene transcription and replication in T cell line, primary peripherical blood lymphocytes and primary macrophages. We show that HPBP is efficient in naïve and HIV-1 AZT-resistant strains. Our results revealed HPBP as a new and potent anti HIV molecule that inhibits transcription of the virus, which has not yet been targeted by HAART and therefore opens new strategies in the treatment of HIV infection.
A rapid chemical method for lysing Arabidopsis cells for protein analysis
Authors: Tsugama Daisuke , Liu Shenkui , Takano Tetsuo 
Published: July 2011

Abstract

Background
Protein extraction is a frequent procedure in biological research. For preparation of plant cell extracts, plant materials usually have to be ground and homogenized to physically break the robust cell wall, but this step is laborious and time-consuming when a large number of samples are handled at once.

Results
We developed a chemical method for lysing Arabidopsis cells without grinding. In this method, plants are boiled for just 10 minutes in a solution containing a Ca2+ chelator and detergent. Cell extracts prepared by this method were suitable for SDS-PAGE and immunoblot analysis. This method was also applicable to genomic DNA extraction for PCR analysis. Our method was applied to many other plant species, and worked well for some of them.

Conclusions
Our method is rapid and economical, and allows many samples to be prepared simultaneously for protein analysis. Our method is useful not only for Arabidopsis research but also research on certain other species.
Reconstruction of extended Petri nets from time series data and its application to signal transduction and to gene regulatory networks
Authors: Durzinsky Markus , Wagler Annegret , Marwan Wolfgang 
Published: July 2011

Abstract

Background
Network inference methods reconstruct mathematical models of molecular or genetic networks directly from experimental data sets. We have previously reported a mathematical method which is exclusively data-driven, does not involve any heuristic decisions within the reconstruction process, and deliveres all possible alternative minimal networks in terms of simple place/transition Petri nets that are consistent with a given discrete time series data set.

Results
We fundamentally extended the previously published algorithm to consider catalysis and inhibition of the reactions that occur in the underlying network. The results of the reconstruction algorithm are encoded in the form of an extended Petri net involving control arcs. This allows the consideration of processes involving mass flow and/or regulatory interactions. As a non-trivial test case, the phosphate regulatory network of enterobacteria was reconstructed using in silico-generated time-series data sets on wild-type and in silico mutants.

Conclusions
The new exact algorithm reconstructs extended Petri nets from time series data sets by finding all alternative minimal networks that are consistent with the data. It suggested alternative molecular mechanisms for certain reactions in the network. The algorithm is useful to combine data from wild-type and mutant cells and may potentially integrate physiological, biochemical, pharmacological, and genetic data in the form of a single model.
Sleep habits and sleep problems among Palestinian students
Authors: Sweileh Waleed M , Ali Iyad A , Sawalha Ansam F , Abu-Taha Adham S , Zyoud Sa'ed H , Al-Jabi Samah W 
Published: July 2011

Abstract

Aim
The aim of this study was to describe sleep habits and sleep problems in a population of undergraduates in Palestine. Association between self-reported sleep quality and self-reported academic achievement was also investigated.

Methods
Sleep habits and problems were investigated using a convenience sample of students from An-Najah National University, Palestine. The study was carried out during spring semester, 2009. A self-administered questionnaire developed based on The Diagnostic and Statistical Manual of Mental Disorders IV criteria and Pittsburgh Sleep Quality Index was used.

Results
400 students with a mean age of 20.2 ± 1.3 were studied. Reported mean duration of night sleep in the study sample was 6.4 ± 1.1 hours. The majority (58.3%) of students went to bed before midnight and 18% of the total sample woke up before 6 am. Sleep latency of more than one hour was present in 19.3% of the students. Two thirds (64.8%) of the students reported having at least one nocturnal awakening per night. Nightmares were the most common parasomnia reported by students. Daytime naps were common and reported in 74.5% of the study sample. Sleep quality was reported as "poor" in only 9.8% and was significantly associated with sleep latency, frequency of nocturnal awakenings, time of going to bed, nightmares but not with academic achievement.

Conclusion
Sleep habits among Palestinian undergraduates were comparable to those reported in European studies. Sleep problems were common and there was no significant association between sleep quality and academic achievement.
High-Dose Chemotherapy With Autologous Hematopoietic Stem-Cell Transplantation in Metastatic Breast Cancer: Overview of Six Randomized Trials
Authors: Berry Donald A. , Ueno Naoto T. , Johnson Marcella M. , Lei Xiudong , Caputo Jean , Smith Dori A. , Yancey Linda J. , Crump Michael , Stadtmauer Edward A. , Biron Pierre , Crown John P. , Schmid Peter , Lotz Jean-Pierre , Rosti Giovanni , Bregni Marco , Demirer Taner 
Published: July 2011

Purpose High doses of effective chemotherapy are compelling if they can be delivered safely. Substantial interest in supporting high-dose chemotherapy with bone marrow or autologous hematopoietic stem-cell transplantation in the 1980s and 1990s led to the initiation of randomized trials to evaluate its effect in the treatment of metastatic breast cancer. Methods We identified six randomized trials in metastatic breast cancer that evaluated high doses of chemotherapy with transplant support versus a control regimen without stem-cell support. We assembled a single database containing individual patient information from these trials. The primary analysis of overall survival was a log-rank test comparing high dose versus control. We also used Cox proportional hazards regression, adjusting for known covariates. We addressed potential treatment differences within subsets of patients. Results The effect of high-dose chemotherapy on overall survival was not statistically different (median, 2.16 v 2.02 years; P = .08). A statistically significant advantage in progression-free survival (median, 0.91 v 0.69 years) did not translate into survival benefit. Subset analyses found little evidence that there are groups of patients who might benefit from high-dose chemotherapy with hematopoietic support. Conclusion Overall survival of patients with metastatic breast cancer in the six randomized trials was not significantly improved by high-dose chemotherapy; any benefit from high doses was small. No identifiable subset of patients seems to benefit from high-dose chemotherapy.
Incremental Value of High-Sensitivity Cardiac Troponin T for Risk Prediction in Patients with Suspected Acute Myocardial Infarction
Authors: Hochholzer Willibald , Reichlin Tobias , Twerenbold Raphael , Stelzig Claudia , Hochholzer Kirsten , Meissner Julia , Haaf Philip , Schaub Nora , Steuer Stephan , Bassetti Stefano , Reiter Miriam , Roost Kathrin , Freidank Heike , Winkler Katrin , Mueller Christian 
Published: July 2011

BACKGROUND
High-sensitivity cardiac troponin assays have better analytical precision and sensitivity than earlier-generation assays when measuring cardiac troponin at low concentrations. We evaluated whether use of a high-sensitivity assay could further improve risk stratification compared with a standard cardiac troponin assay.

METHODS
We enrolled consecutive patients presenting with acute chest pain, 30% of whom were diagnosed with acute coronary syndrome. Blood samples were drawn at the time of presentation. We measured cardiac troponin T with a standard fourth-generation assay (cTnT) and a high-sensitivity assay (hs-cTnT) (both Roche Diagnostics) and followed the patients for 24 months.

RESULTS
Of the 1159 patients, 76 died and 42 developed an acute myocardial infarction (AMI). Prognostic accuracy of hs-cTnT for death was significantly higher [area under ROC curve (AUC) 0.79, 95% CI 0.74–0.84] than that of cTnT (AUC 0.69, 95% CI 0.62–0.76; P &lt; 0.001). After adjustment for Thrombolysis in Myocardial Infarction (TIMI) risk score (that included the cTnT assay result), hs-cTnT above the 99th percentile (0.014 μg/L) was associated with a hazard ratio for death of 2.60 (95% CI 1.42–4.74). Addition of hs-cTnT to the risk score improved the reclassification of patients (net reclassification improvement 0.91; 95% CI 0.67–1.14; P &lt; 0.001). Subgroup analyses showed that this effect resulted from the better classification of patients without AMI at time of testing. hs-cTnT outperformed cTnT in the prediction of AMI during follow-up (P=0.02), but was not independently predictive for this endpoint.

CONCLUSIONS
Concentrations of hs-cTnT &gt;0.014 μg/L improve the prediction of death but not subsequent AMI in unselected patients presenting with acute chest pain.
Experimental evidence of the potential use of erythropoietin by intranasal administration as a neuroprotective agent in cerebral hypoxia
Authors: Merelli Amalia , Caltana Laura , Lazarowski Alberto , Brusco Alicia 
Published: July 2011

Abstract
Stroke is a major human health problem without efficient available therapeutics. Ischemic brain injury can induce cell death as well as upregulation of endogenous adaptive mechanisms depending on the severity and duration of hypoxia, and the activity of transcription factors, such as hypoxia inducible factor 1-α (HIF-1α). HIF-1α induces gene expression as multidrug resistance (MDR-1) gene associated with drug-refractory phenotype, as well as erythropoietin (Epo) and erythropoietin receptor (Epo-R) associated with O2 supply. The spontaneous stimulation of the Epo/Epo-R system is not enough for brain protection. Therefore, administration of exogenous recombinant human Epo (rHu-Epo) was suggested as an alternative therapy in stroke. In several experimental models of brain hypoxia, Epo and Epo variants, including rHu-Epo, showed neuroprotective effects. Intranasal administration of these Epo-compounds can reach the central nervous system and protect the brain against ischemia, avoiding hematopoietic effects. However, it has been reported that high expression of Epo-R in neurons must be available to be activated by Epo. According to these considerations, intranasal delivery of rHu-Epo could be an interesting approach in the treatment of cerebral hypoxias avoiding both (i) adverse peripheral effects of treatment with Epo in stroke, and (ii) the pharmacoresistant phenotype depending on MDR-1 expression.