bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of catecholamines on hepatic and skeletal muscle mitochondrial respiration after prolonged exposure to faecal peritonitis in pigs
Authors: Vuda Madhusudanarao , Brander Lukas , Schröder Ralph , Jakob Stephan M , Takala Jukka , Djafarzadeh Siamak 
Published: April 2011

Use of norepinephrine to increase blood pressure in septic animals has been associated with increased efficiency of hepatic mitochondrial respiration. The aim of this study was to evaluate whether the same effect could be reproduced in isolated hepatic mitochondria after prolonged in vivo exposure to faecal peritonitis. Eighteen pigs were randomized to 27 h of faecal peritonitis and to a control condition (n = 9 each group). At the end, hepatic mitochondria were isolated and incubated for one hour with either norepinephrine or placebo, with and without pretreatment with the specific receptor antagonists prazosin and yohimbine. Mitochondrial state 3 and state 4 respiration were measured for respiratory chain complexes I and II, and state 3 for complex IV using high-resolution respirometry, and respiratory control ratios were calculated. Additionally, skeletal muscle mitochondrial respiration was evaluated after incubation with norepinephrine and dobutamine with and without the respective antagonists (atenolol, propranolol and phentolamine for dobutamine). Faecal peritonitis was characterized by decreasing blood pressure and stroke volume, and maintained systemic oxygen consumption. Neither faecal peritonitis nor any of the drugs or drug combinations had measurable effects on hepatic or skeletal muscle mitochondrial respiration. Norepinephrine did not improve the efficiency of complex I- and complex II-dependent isolated hepatic mitochondrial respiration [respiratory control ratio (RCR) complex I: 5.6 ± 5.3 (placebo) vs. 5.4 ± 4.6 (norepinephrine) in controls and 2.7 ± 2.1 (placebo) vs. 2.9 ± 1.5 (norepinephrine) in septic animals; RCR complex II: 3.5 ± 2.0 (placebo) vs. 3.5 ± 1.8 (norepinephrine) in controls; 2.3 ± 1.6 (placebo) vs. 2.2 ± 1.1 (norepinephrine) in septic animals]. Prolonged faecal peritonitis did not affect either hepatic or skeletal muscle mitochondrial respiration. Subsequent incubation of isolated mitochondria with norepinephrine and dobutamine did not significantly influence their respiration.
Mathematical modelling and experimental study of a solar distillation system
Authors: Mahian O , Kianifar A 
Published: April 2011

The production of potable water from saltwater or brackish water using solar distillation has been practised for many years in different parts of the world. However, little attention has been paid to the feasibility of this technique in Iran. In this work, a solar still with a basin area of 0.9 m2 and a glass cover in the form of a pyramid has been designed and constructed, and its performance is studied experimentally in Mashhad, Iran. Also, the performance of the solar still is modelled where a small fan was utilized to enhance the daily productivity of freshwater. In addition to the effect of forced convection caused by a fan, the effects of the water depth, the insulation thickness of the basin base, and the wind velocity have been investigated. The empirical results have been compared with the results obtained from the mathematical model and good agreement has been obtained. The results show that the use of a low-cost fan with negligible power can be an effective and economical way of enhancing the evaporation rate and hence freshwater production. Based on the mathematical model, the daily productivity of freshwater increases up to ∼ 56 per cent at a Reynolds number of 35 000. Finally, an effective range for the wind velocity as well as insulation thickness is presented in order to optimize the production rate of freshwater.
Constitutive Notch pathway activation in murine ZMYM2-FGFR1–induced T-cell lymphomas associated with atypical myeloproliferative disease
Authors: Ren MingQiang , Cowell John K. 
Published: April 2011

Abstract
The ZMYM2-FGFR1 (formerly known as ZNF198-FGFR1) fusion kinase induces stem cell leukemia–lymphoma syndrome (SCLL), a hematologic malignancy characterized by rapid transformation to acute myeloid leukemia and T-lymphoblastic lymphoma. In the present study, we demonstrate frequent, constitutive activation of Notch1 and its downstream target genes in T-cell lymphomas that arose in a murine model of ZMYM2-FGFR1 SCLL. Notch up-regulation was also demonstrated in human SCLL- and FGFR1OP2-FGFR1-expressing KG-1 cells. To study the role of Notch in T-cell lymphomagenesis, we developed a highly tumorigenic cell line from ZMYM2-FGFR1–expressing cells. Pharmacologic inhibition of Notch signaling in these cells using γ-secretase inhibitors significantly delayed leukemogenesis in vivo. shRNA targeting of Notch1, as well as c-promoter–binding factor 1 (CBF1) and mastermind-like 1 (MAML1), 2 essential cofactors involved in transcriptional activation of Notch target genes, also significantly delayed or inhibited tumorigenesis in vivo. Mutation analysis demonstrated that 5′ promoter deletions and alternative promoter usage were responsible for constitutive activation of Notch1 in all T-cell lymphomas. These data demonstrate the importance of Notch signaling in the etiology of SCLL, and suggest that targeting this pathway could provide a novel strategy for molecular therapies to treat SCLL patients.
Overexpression of microRNA-16-2 contributes to the abnormal erythropoiesis in polycythemia vera
Authors: Guglielmelli Paola , Tozzi Lorenzo , Bogani Costanza , Iacobucci Ilaria , Ponziani Vanessa , Martinelli Giovanni , Bosi Alberto , Vannucchi Alessandro M. 
Published: April 2011

Abstract
Deregulated expression of microRNAs is associated with neoplasia. Here, we show that mature miR-16 levels are abnormally increased in CD34+ cells of patients with polycythemia vera as a consequence of preferential expression of miR-16-2 on chromosome 3 rather than of miR-16-1 on chromosome 13. Forced expression of miRNA-16 in normal CD34+ cells stimulated erythroid cell proliferation and maturation. Conversely, exposure of polycythemia vera CD34+ cells to small interfering RNA against pre-miR-16-2 reduced erythroid colonies and largely prevented formation of erythropoietin-independent colonies; myeloid progenitors remained unaffected. Experiments with knock down of JAK2 indicated that overexpression of miR-16 was independent of JAK/STAT pathway activation. Mice injected with an miR-16 antagomir showed a blunted erythroid response to exogenous erythropoietin, which indicates a role of miR-16 in normal erythropoiesis. These data suggest that deregulation of miR-16-2 contributes to abnormal expansion of erythroid lineage in polycythemia vera. However, the mechanisms for miR-16-2 overexpression remain to be elucidated, because no genetic abnormalities at the miR-16-2 locus were discovered.
Discovering time-lagged rules from microarray data using gene profile classifiers
Authors: Gallo Cristian A , Carballido Jessica A , Ponzoni Ignacio 
Published: April 2011

Abstract

Background
Gene regulatory networks have an essential role in every process of life. In this regard, the amount of genome-wide time series data is becoming increasingly available, providing the opportunity to discover the time-delayed gene regulatory networks that govern the majority of these molecular processes.

Results
This paper aims at reconstructing gene regulatory networks from multiple genome-wide microarray time series datasets. In this sense, a new model-free algorithm called GRNCOP2 (G ene R egulatory N etwork inference by C ombinatorial OP timization 2), which is a significant evolution of the GRNCOP algorithm, was developed using combinatorial optimization of gene profile classifiers. The method is capable of inferring potential time-delay relationships with any span of time between genes from various time series datasets given as input. The proposed algorithm was applied to time series data composed of twenty yeast genes that are highly relevant for the cell-cycle study, and the results were compared against several related approaches. The outcomes have shown that GRNCOP2 outperforms the contrasted methods in terms of the proposed metrics, and that the results are consistent with previous biological knowledge. Additionally, a genome-wide study on multiple publicly available time series data was performed. In this case, the experimentation has exhibited the soundness and scalability of the new method which inferred highly-related statistically-significant gene associations.

Conclusions
A novel method for inferring time-delayed gene regulatory networks from genome-wide time series datasets is proposed in this paper. The method was carefully validated with several publicly available data sets. The results have demonstrated that the algorithm constitutes a usable model-free approach capable of predicting meaningful relationships between genes, revealing the time-trends of gene regulation.
PEX11β induces peroxisomal gene expression and alters peroxisome number during early Xenopus laevis development
Authors: Fox Mark A , Walsh Logan A , Nieuwesteeg Michelle , Damjanovski Sashko 
Published: April 2011

Abstract

Background
Peroxisomes are organelles whose roles in fatty acid metabolism and reactive oxygen species elimination have contributed much attention in understanding their origin and biogenesis. Many studies have shown that de novo peroxisome biogenesis is an important regulatory process, while yeast studies suggest that total peroxisome numbers are in part regulated by proteins such as Pex11, which can facilitate the division of existing peroxisomes. Although de novo biogenesis and divisions are likely important mechanisms, the regulation of peroxisome numbers during embryonic development is poorly understood. Peroxisome number and function are particularly crucial in oviparous animals such as frogs where large embryonic yolk and fatty acid stores must be quickly metabolized, and resulting reactive oxygen species eliminated. Here we elucidate the role of Pex11β in regulating peroxisomal gene expression and number in Xenopus laevis embryogenesis.

Results
Microinjecting haemagglutinin (HA) tagged Pex11β in early embryos resulted in increased RNA levels for peroxisome related genes PMP70 and catalase at developmental stages 10 and 20, versus uninjected embryos. Catalase and PMP70 proteins were found in punctate structures at stage 20 in control embryos, whereas the injection of ectopic HA-Pex11β induced their earlier localization in punctate structures at stage 10. Furthermore, the peroxisomal marker GFP-SKL, which was found localized as peroxisome-like structures at stage 20, was similarly found at stage 10 when co-microinjected with HA-Pex11β.

Conclusions
Overexpressed Pex11β altered peroxisomal gene levels and induced the early formation of peroxisomes-like structures during development, both of which demonstrate that Pex11β may be a key regulator of peroxisome number in early Xenopus embryos.
Identification and characterisation of a novel adhesin Ifp in Yersinia pseudotuberculosis
Authors: Strong Philippa CR , Hinchliffe Stewart J , Patrick Hannah , Atkinson Steve , Champion Olivia L , Wren Brendan W 
Published: April 2011

Abstract

Background
In order to identify new virulence determinants in Y. pseudotuberculosis a comparison between its genome and that of Yersinia pestis was undertaken. This reveals dozens of pseudogenes in Y. pestis, which are still putatively functional in Y. pseudotuberculosis and may be important in the enteric lifestyle. One such gene, YPTB1572 in the Y. pseudotuberculosis IP32953 genome sequence, encodes a protein with similarity to invasin, a classic adhesion/invasion protein, and to intimin, the attaching and effacing protein from enteropathogenic (EPEC) and enterohaemorraghic (EHEC) Escherichia coli.

Results
We termed YPTB1572 Ifp (Intimin family protein) and show that it is able to bind directly to human HEp-2 epithelial cells. Cysteine and tryptophan residues in the C-terminal region of intimin that are essential for function in EPEC and EHEC are conserved in Ifp. Protein binding occurred at distinct foci on the HEp-2 cell surface and can be disrupted by mutation of a single cysteine residue at the C-terminus of the protein. Temporal expression analysis using lux reporter constructs revealed that ifp is expressed at late log phase at 37°C in contrast to invasin, suggesting that Ifp is a late stage adhesin. An ifp defined mutant showed a reduction in adhesion to HEp-2 cells and was attenuated in the Galleria mellonella infection model.

Conclusion
A new Y. pseudotuberculosis adhesin has been identified and characterised. This Ifp is a new member in the family of invasin/intimin outer membrane adhesins.
The analysis of para-cresol production and tolerance in Clostridium difficile 027 and 012 strains
Authors: Dawson Lisa F , Donahue Elizabeth H , Cartman Stephen T , Barton Richard H , Bundy Jake , McNerney Ruth , Minton Nigel P , Wren Brendan W 
Published: April 2011

Abstract

Background

Clostridium difficile is the major cause of antibiotic associated diarrhoea and in recent years its increased prevalence has been linked to the emergence of hypervirulent clones such as the PCR-ribotype 027. Characteristically, C. difficile infection (CDI) occurs after treatment with broad-spectrum antibiotics, which disrupt the normal gut microflora and allow C. difficile to flourish. One of the relatively unique features of C. difficile is its ability to ferment tyrosine to para-cresol via the intermediate para-hydroxyphenylacetate (p-HPA). P-cresol is a phenolic compound with bacteriostatic properties which C. difficile can tolerate and may provide the organism with a competitive advantage over other gut microflora, enabling it to proliferate and cause CDI. It has been proposed that the hpdBCA operon, rarely found in other gut microflora, encodes the enzymes responsible for the conversion of p-HPA to p-cresol.

Results
We show that the PCR-ribotype 027 strain R20291 quantitatively produced more p-cresol in-vitro and was significantly more tolerant to p-cresol than the sequenced strain 630 (PCR-ribotype 012). Tyrosine conversion to p-HPA was only observed under certain conditions. We constructed gene inactivation mutants in the hpdBCA operon in strains R20291 and 630Δerm which curtails their ability to produce p-cresol, confirming the role of these genes in p-cresol production. The mutants were equally able to tolerate p-cresol compared to the respective parent strains, suggesting that tolerance to p-cresol is not linked to its production.

Conclusions

C. difficile converts tyrosine to p-cresol, utilising the hpdBCA operon in C. difficile strains 630 and R20291. The hypervirulent strain R20291 exhibits increased production of and tolerance to p-cresol, which may be a contributory factor to the virulence of this strain and other hypervirulent PCR-ribotype 027 strains.
Growth of breast cancer recurrences assessed by consecutive MRI
Authors: Millet Ingrid , Bouic-Pages Emmanuelle , Hoa Denis , Azria David , Taourel Patrice 
Published: April 2011

Abstract

Background
Women with a personal history of breast cancer have a high risk of developing an ipsi- or contralateral recurrence. We aimed to compare the growth rate of primary breast cancer and recurrences in women who had undergone prior breast magnetic resonance imaging (MRI).

Methods
Three hundred and sixty-two women were diagnosed with breast cancer and had undergone breast MRI at the time of diagnosis in our institution (2005 - 2009). Among them, 37 had at least one prior breast MRI with the lesion being visible but not diagnosed as cancer. A linear regression of tumour volume measured on MRI scans and time data was performed using a generalized logistic model to calculate growth rates. The primary objective was to compare the tumour growth rate of patients with either primary breast cancer (no history of breast cancer) or ipsi- or contralateral recurrences of breast cancer.

Results
Twenty women had no history of breast cancer and 17 patients were diagnosed as recurrences (7 and 10 were ipsi- and contralateral, respectively). The tumour growth rate was higher in contralateral recurrences than in ipsilateral recurrences (growth rate [10-3 days-1] 3.56 vs 1.38, p < .001) or primary cancer (3.56 vs 2.09, p = 0.01). Differences in tumour growth were not significant for other patient-, tumour- or treatment-related characteristics.

Conclusions
These findings suggest that contralateral breast cancer presents accelerated growth compared to ipsilateral recurrences or primary breast events.
In vivo monitoring of fetoplacental Vegfr2 gene activity in a murine pregnancy model using a Vegfr2-luc reporter gene and bioluminescent imaging
Authors: Greene Jonathan M , Dunaway Chad W , Bowers Susan D , Rude Brian J , Feugang Jean M , Ryan Peter L 
Published: April 2011

Abstract

Background
Vascular endothelial growth factor receptor-2 (VEGFR2) plays a pivotal role in angiogenesis by eliciting vascular endothelial cell growth when bound to VEGF, a powerful pro-angiogenic ligand. While Vegf and Vegfr2 are expressed throughout gestation, the latter third of gestation in mice is characterized by a marked increase in fetoplacental angiogenesis. Thus, the objective of this study was to determine the feasibility of monitoring fetoplacental Vegfr2 gene activity non-invasively using a Vegfr2-luc reporter transgenic mouse and bioluminescent imaging.

Methods
Imaging parameters were optimized using two wild-type (WT) females, bearing Vegfr2-luc fetuses. Then, seven WT females, bred to Vegfr2-luc males, were imaged from gestational day (GD) 12 to 18 to determine the usefulness of the Vegfr2-luc mouse as a model for studying fetoplacental Vegfr2 activity during pregnancy. Semi-quantitative RT-PCR of Vegfr2 was also performed on whole fetoplacental units during this time. Additionally, resultant neonates were imaged at postnatal day (PND) 7, 14 and 21 to monitor Vegfr2 activity during post-natal development.

Results
Fetoplacental Vegfr2 gene activity was detected as light emissions beginning on GD 12 of gestation and increased throughout the imaging period (P < 0.05), and this paralleled the Vegfr2 mRNA data obtained from RT-PCR analysis. A decline in fetoplacental light emissions was associated with a poor pregnancy outcome in one pregnancy, indicating that this approach has potential use for studies monitoring pregnancy well being. Additionally, neonatal Vegfr2 activity was detected at PND 7, 14 and 21 but declined with time (P < 0.0001).

Conclusions

In utero fetoplacental Vegfr2 gene activity was monitored longitudinally in a quantitative manner using a luciferase reporter gene and bioluminescent imaging during the latter third of gestation. This study demonstrates the feasibility of using the Vegfr2-luc mouse to monitor late gestation fetoplacental angiogenic activity under normal and experimental conditions. Additionally, neonatal Vegfr2 gene activity was monitored for three weeks postpartum, allowing continuous monitoring of Vegfr2 activity during the latter third of gestation and postnatal development within the same animals.
Architectures of archaeal GINS complexes, essential DNA replication initiation factors
Authors: Oyama Takuji , Ishino Sonoko , Fujino Seiji , Ogino Hiromi , Shirai Tsuyoshi , Mayanagi Kouta , Saito Mihoko , Nagasawa Naoko , Ishino Yoshizumi , Morikawa Kosuke 
Published: April 2011

Abstract

Background
In the early stage of eukaryotic DNA replication, the template DNA is unwound by the MCM helicase, which is activated by forming a complex with the Cdc45 and GINS proteins. The eukaryotic GINS forms a heterotetramer, comprising four types of subunits. On the other hand, the archaeal GINS appears to be either a tetramer formed by two types of subunits in a 2:2 ratio (α2β2) or a homotetramer of a single subunit (α4). Due to the low sequence similarity between the archaeal and eukaryotic GINS subunits, the atomic structures of the archaeal GINS complexes are attracting interest for comparisons of their subunit architectures and organization.

Results
We determined the crystal structure of the α2β2 GINS tetramer from Thermococcus kodakaraensis (TkoGINS), comprising Gins51 and Gins23, and compared it with the reported human GINS structures. The backbone structure of each subunit and the tetrameric assembly are similar to those of human GINS. However, the location of the C-terminal small domain of Gins51 is remarkably different between the archaeal and human GINS structures. In addition, TkoGINS exhibits different subunit contacts from those in human GINS, as a consequence of the different relative locations and orientations between the domains. Based on the GINS crystal structures, we built a homology model of the putative homotetrameric GINS from Thermoplasma acidophilum (TacGINS). Importantly, we propose that a long insertion loop allows the differential positioning of the C-terminal domains and, as a consequence, exclusively leads to the formation of an asymmetric homotetramer rather than a symmetrical one.

Conclusions
The DNA metabolizing proteins from archaea are similar to those from eukaryotes, and the archaeal multi-subunit complexes are occasionally simplified versions of the eukaryotic ones. The overall similarity in the architectures between the archaeal and eukaryotic GINS complexes suggests that the GINS function, directed through interactions with other protein components, is basically conserved. On the other hand, the different subunit contacts, including the locations and contributions of the C-terminal domains to the tetramer formation, imply the possibility that the archaeal and eukaryotic GINS complexes contribute to DNA unwinding reactions by significantly different mechanisms in terms of the atomic details.
TRESK Channel Contribution to Nociceptive Sensory Neurons Excitability: Modulation by Nerve Injury
Authors: Tulleuda Astrid , Cokic Barbara , Callejo Gerard , Saiani Barbara , Serra Jordi , Gasull Xavier 
Published: April 2011

Background: Neuronal hyperexcitability is a crucial phenomenon underlying spontaneous and evoked pain. In invertebrate nociceptors, the S-type leak K+ channel (analogous to TREK-1 in mammals) plays a critical role of in determining neuronal excitability following nerve injury. Few data are available on the role of leak K2P channels after peripheral axotomy in mammals. Results: Here we describe that rat sciatic nerve axotomy induces hyperexcitability of L4-L5 DRG sensory neurons and decreases TRESK (K2P18.1) expression, a channel with a major contribution to total leak current in DRGs. While the expression of other channels from the same family did not significantly change, injury markers ATF3 and Cacna2d1 were highly upregulated. Similarly, acute sensory neuron dissociation ( in vitro axotomy) produced marked hyperexcitability and similar total background currents compared with neurons injured in vivo. In addition, the sanshool derivative IBA, which blocked TRESK currents in transfected HEK293 cells and DRGs, increased intracellular calcium in 49% of DRG neurons in culture. Most IBA-responding neurons (71%) also responded to the TRPV1 agonist capsaicin, indicating that they were nociceptors. Additional evidence of a biological role of TRESK channels was provided by behavioral evidence of pain (flinching and licking), in vivo electrophysiological evidence of C-nociceptor activation following IBA injection in the rat hindpaw, and increased sensitivity to painful pressure after TRESK knockdown in vivo. Conclusions: In summary, our results clearly support an important role of TRESK channels in determining neuronal excitability in specific DRG neurons subpopulations, and show that axonal injury down-regulates TRESK channels, therefore contributing to neuronal hyperexcitability.