bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network orientation via shortest paths
Authors: Silverbush Dana , Sharan Roded 
Published: January 2014

AbstractThe graph orientation problem calls for orienting the edges of a graph so as to maximize the number of pre-specified source–target vertex pairs that admit a directed path from the source to the target. Most algorithmic approaches to this problem share a common preprocessing step, in which the input graph is reduced to a tree by repeatedly contracting its cycles. Although this reduction is valid from an algorithmic perspective, the assignment of directions to the edges of the contracted cycles becomes arbitrary, and the connecting source–target paths may be arbitrarily long. In the context of biological networks, the connection of vertex pairs via shortest paths is highly motivated, leading to the following problem variant: given a graph and a collection of source–target vertex pairs, assign directions to the edges so as to maximize the number of pairs that are connected by a shortest (in the original graph) directed path. This problem is NP-complete and hard to approximate to within sub-polynomial factors. Here we provide a first polynomial-size integer linear program formulation for this problem, which allows its exact solution in seconds on current networks. We apply our algorithm to orient protein–protein interaction networks in yeast and compare it with two state-of-the-art algorithms. We find that our algorithm outperforms previous approaches and can orient considerable parts of the network, thus revealing its structure and function.Availability and implementation: The source code is available at www.cs.tau.ac.il/∼roded/shortest.zip.Contact: roded@post.tau.ac.il
PGP: parallel prokaryotic proteogenomics pipeline for MPI clusters, high-throughput batch clusters and multicore workstations
Authors: Tovchigrechko Andrey , Venepally Pratap , Payne Samuel H. 
Published: January 2014

AbstractSummary: We present the first public release of our proteogenomic annotation pipeline. We have previously used our original unreleased implementation to improve the annotation of 46 diverse prokaryotic genomes by discovering novel genes, post-translational modifications and correcting the erroneous annotations by analyzing proteomic mass-spectrometry data.This public version has been redesigned to run in a wide range of parallel Linux computing environments and provided with the automated configuration, build and testing facilities for easy deployment and portability.Availability and implementation: Source code is freely available from https://bitbucket.org/andreyto/proteogenomics under GPL license. It is implemented in Python and C++. It bundles the Makeflow engine to execute the workflows.Contact: atovtchi@jcvi.org
Trypanosome MKT1 and the RNA-binding protein ZC3H11: interactions and potential roles in post-transcriptional regulatory networks
Authors: Singh Aditi , Minia Igor , Droll Dorothea , Fadda Abeer , Clayton Christine , Erben Esteban 
Published: January 2014

Abstract
The trypanosome zinc finger protein ZC3H11 binds to AU-rich elements in mRNAs. It is essential for survival of the mammalian-infective bloodstream form, where it stabilizes several mRNAs including some encoding chaperones, and is also required for stabilization of chaperone mRNAs during the heat-shock response in the vector-infective procyclic form. When ZC3H11 was artificially ‘tethered’ to a reporter mRNA in bloodstream forms it increased reporter expression. We here show that ZC3H11 interacts with trypanosome MKT1 and PBP1, and that domains required for both interactions are necessary for function in the bloodstream-form tethering assay. PBP1 interacts with MKT1, LSM12 and poly(A) binding protein, and localizes to granules during parasite starvation. All of these proteins are essential for bloodstream-form trypanosome survival and increase gene expression in the tethering assay. MKT1 is cytosolic and polysome associated. Using a yeast two-hybrid screen and tandem affinity purification we found that trypanosome MKT1 interacts with multiple RNA-binding proteins and other potential RNA regulators, placing it at the centre of a post-transcriptional regulatory network. A consensus interaction sequence, H(E/D/N/Q)PY, was identified. Recruitment of MKT1-containing regulatory complexes to mRNAs via sequence-specific mRNA-binding proteins could thus control several different post-transcriptional regulons.
The influence of CpG and UpA dinucleotide frequencies on RNA virus replication and characterization of the innate cellular pathways underlying virus attenuation and enhanced replication
Authors: Atkinson Nicky J. , Witteveldt Jeroen , Evans David J. , Simmonds Peter 
Published: January 2014

Abstract
Most RNA viruses infecting mammals and other vertebrates show profound suppression of CpG and UpA dinucleotide frequencies. To investigate this functionally, mutants of the picornavirus, echovirus 7 (E7), were constructed with altered CpG and UpA compositions in two 1.1–1.3 Kbase regions. Those with increased frequencies of CpG and UpA showed impaired replication kinetics and higher RNA/infectivity ratios compared with wild-type virus. Remarkably, mutants with CpGs and UpAs removed showed enhanced replication, larger plaques and rapidly outcompeted wild-type virus on co-infections. Luciferase-expressing E7 sub-genomic replicons with CpGs and UpAs removed from the reporter gene showed 100-fold greater luminescence. E7 and mutants were equivalently sensitive to exogenously added interferon-β, showed no evidence for differential recognition by ADAR1 or pattern recognition receptors RIG-I, MDA5 or PKR. However, kinase inhibitors roscovitine and C16 partially or entirely reversed the attenuated phenotype of high CpG and UpA mutants, potentially through inhibition of currently uncharacterized pattern recognition receptors that respond to RNA composition. Generating viruses with enhanced replication kinetics has applications in vaccine production and reporter gene construction. More fundamentally, the findings introduce a new evolutionary paradigm where dinucleotide composition of viral genomes is subjected to selection pressures independently of coding capacity and profoundly influences host–pathogen interactions.
Golgi- and Trans-Golgi Network-Mediated Vesicle Trafficking Is Required for Wax Secretion from Epidermal Cells
Authors: McFarlane Heather E. , Watanabe Yoichiro , Yang Weili , Huang Yan , Ohlrogge John , Samuels A. Lacey 
Published: January 2014

AbstractLipid secretion from epidermal cells to the plant surface is essential to create the protective plant cuticle. Cuticular waxes are unusual secretory products, consisting of a variety of highly hydrophobic compounds including saturated very-long-chain alkanes, ketones, and alcohols. These compounds are synthesized in the endoplasmic reticulum (ER) but must be trafficked to the plasma membrane for export by ATP-binding cassette transporters. To test the hypothesis that wax components are trafficked via the endomembrane system and packaged in Golgi-derived secretory vesicles, Arabidopsis (Arabidopsis thaliana) stem wax secretion was assayed in a series of vesicle-trafficking mutants, including gnom like1-1 (gnl1-1), transport particle protein subunit120-4, and echidna (ech). Wax secretion was dependent upon GNL1 and ECH. Independent of secretion phenotypes, mutants with altered ER morphology also had decreased wax biosynthesis phenotypes, implying that the biosynthetic capacity of the ER is closely related to its structure. These results provide genetic evidence that wax export requires GNL1- and ECH-dependent endomembrane vesicle trafficking to deliver cargo to plasma membrane-localized ATP-binding cassette transporters.
Inhibition of soluble epoxide hydrolase is renoprotective in 5/6 nephrectomized Ren‐2 transgenic hypertensive rats
Authors: Kujal Petr , Čertíková Chábová Vera , Škaroupková Petra , Husková Zuzana , Vernerová Zdena , Kramer Herbert J , Walkowska Agnieszka , Kompanowska‐Jezierska Elzbieta , Sadowski Janusz , Kitada Kento , Nishiyama Akira , Hwang Sung H , Hammock Bruce D , Imig John D , Červenka Ludek 
Published: January 2014

Summary

The aim of the present study was to test the hypothesis that increasing kidney tissue concentrations of epoxyeicosatrienoic acids (EETs) by preventing their degradation to the biologically inactive dihydroxyeicosatrienoic acids (DHETEs) using blockade of soluble epoxide hydrolase (sEH) would attenuate the progression of chronic kidney disease (CKD).

Ren‐2 transgenic rats (TGR) after 5/6 renal mass reduction (5/6 NX) served as a model of CKD associated with angiotensin (Ang) II‐dependent hypertension. Soluble epoxide hydrolase was inhibited using cis‐4‐[4‐(3‐adamantan‐1‐yl‐ureido)cyclohexyloxy]benzoic acid (c‐AUCB; 3 mg/L drinking water) for 20 weeks after 5/6 NX. Sham‐operated normotensive transgene‐negative Hannover Sprague‐Dawley (HanSD) rats served as controls.

When applied in TGR subjected to 5/6 NX, c‐AUCB treatment improved survival rate, prevented the increase in blood pressure, retarded the progression of cardiac hypertrophy, reduced proteinuria and the degree of glomerular and tubulointerstitial injury and reduced glomerular volume. All these organ‐protective actions were associated with normalization of the intrarenal EETs : DHETEs ratio, an index of the availability of biologically active EETs, to levels observed in sham‐operated HanSD rats. There were no significant concurrent changes of increased intrarenal AngII content.

Together, these results show that 5/6 NX TGR exhibit a profound deficiency of intrarenal availability of active epoxygenase metabolites (EETs), which probably contributes to the progression of CKD in this model of AngII‐dependent hypertension, and that restoration of intrarenal availability of EETs using long‐term c‐AUCB treatment exhibits substantial renoprotective actions.
Resveratrol and vitamin E rescue valproic acid‐induced teratogenicity: The mechanism of action
Authors: Hsieh Chiu‐Lan , Chen Kuan‐Chou , Lin Ping‐Xiao , Peng Chiung‐Chi , Peng Robert Y 
Published: January 2014

Summary

Valproic acid (VPA) induces haemorrhagic liposis of the cervical muscles in the chicken embryo model (CEM). Vitamin E and resveratrol (RV) exhibit prominent anti‐oxidative and glutathione (GSH)‐protecting effects.

In the present study we hypothesized that vitamin E and RV would ameliorate VPA induced haemorrhagic liposis in chick embryos. To this end, 120 Day 0 fertilized eggs were divided into 10 groups (n = 12 in each). The effects of different combinations of VPA (60 mmol/L), RV (0.2 and 2.0 mmol/L) and vitamin E (0.2 and 2.0 mmol/L) applied to Hamburger and Hamilton (HH) Stage 10 (Day 1.5) embryos were tested in the CEM using established methods.

Both RV and vitamin E (both at 2.0 mmol/L) effectively rescued neural tube defects in the early stage CEM and inhibited the malformation rate compared with that in the control group (8.4% and 5.0% vs 36.5 ± 3.0%, respectively; P < 0.05) and suppressed serum homocysteine and S‐adenosylhomocysteine concentrations, downregulated cervical muscular carnitine, triglycerides, H2O2, malondialdehyde, interleukin‐6 and ACC expression (P < 0.05 for all) and upregulated CPT1 expression and GSH (P < 0.05 for both).

The haemorrhagic liposis of cervical muscles can be alleviated by RV and vitamin E. It appears that the main mechanism of action of RV and vitamin E in rescuing VPA‐induced teratogenicity is through the suppression of reactive oxygen species and upregulation of GSH.
Endothelial and neuronal nitric oxide synthases variably modulate the oestrogen‐mediated control of blood pressure and cardiovascular autonomic control
Authors: El‐Mas Mahmoud M , Abdel‐Rahman Abdel A 
Published: January 2014

Summary

We have shown previously that long‐term oestrogen (E2) replacement lowers blood pressure (BP) and improves cardiovascular autonomic control in ovariectomized (OVX) rats. In the present study, we investigated whether constitutive and/or inducible (i) nitric oxide synthase (NOS) modulate these E2 effects.

We evaluated changes in BP, myocardial contractility index (dP/dtmax) and power spectral indices of haemodynamic variability following selective inhibition of endothelial (e) NOS with N5‐(1‐iminoethyl)‐ l‐ornithine (l‐NIO), neuronal (n) NOS with Nω‐propyl‐l‐arginine (NPLA) or iNOS with 1400W in telemetered OVX rats treated for 16 weeks with (OVXE2) or without (control; OVXC) E2.

The OVXE2 rats exhibited: (i) reduced BP and increased dP/dtmax; (ii) cardiac parasympathetic dominance, as reflected by the reduced low‐frequency (LF; 0.25–0.75 Hz)/high‐frequency (HF; 0.75–3 Hz) ratio of interbeat intervals (IBILF/HF); and (iii) reduced LF oscillations of systolic BP, suggesting a reduced vasomotor sympathetic tone. Inhibition of eNOS (l‐NIO; 20 mg/kg, i.p.) elicited a shorter‐lived pressor response in OVXE2 than OVXC, rats along with reductions in dP/dtmax and increases in the spectral index of spontaneous baroreflex sensitivity (index α). Treatment with 1 mg/kg, i.p., NPLA reduced BP and increased the IBILF/HF ratio in OVXE2 but not OVXC rats. The iNOS inhibitor 1400W (5 mg/kg, i.p.) caused no haemodynamic changes in OVXC or OVXE2 rats.

Overall, constitutive NOS isoforms exert restraining tonic modulatory BP effects that encompass eNOS‐mediated reductions and nNOS‐mediated elevations in BP in OVXE2 rats. Baroreflex facilitation and dP/dtmax reductions may account for the shorter pressor action of l‐NIO in E2‐treated, compared with untreated, OVX rats.
Mathematical modelling of enteric neural motor patterns
Authors: Chambers Jordan D , Thomas Evan A , Bornstein Joel C 
Published: January 2014

Summary

The enteric nervous system modulates intestinal behaviours, such as motor patterns and secretion. Although much is known about different types of neurons and simple reflexes in the intestine, it remains unclear how complex behaviours are generated.

Mathematical modelling is an important tool for assisting the understanding of how the neurons and reflexes can be pieced together to generate intestinal behaviours.

Models have identified a functional role for slow excitatory post‐synaptic potentials (EPSPs) by distinguishing between fast and slow EPSPs in the ascending excitation reflex. These models also discovered coordinated firing of similarly located neurons as emergent properties of feed‐forward networks of interneurons in the intestine. A model of the recurrent network of intrinsic sensory neurons identified important control mechanisms to prevent uncontrolled firing due to positive feedback and that the interaction between these control mechanisms and slow EPSPs is necessary for the networks to encode ongoing sensory stimuli. This model also showed that such networks may mediate migrating motor complexes.

A network model of vasoactive intestinal peptide neurons in the submucosal plexus found this relatively sparse recurrent network could produce uncontrolled firing under conditions that appear to be related to cholera toxin‐induced hypersecretion.

Abstract modelling of the intestinal fed‐state motor patterns has identified how stationary contractions can arise from a polarized network.

These models have also helped predict and/or explained pharmacological evidence for two rhythm generators and the requirement of feedback from contractions in the circular muscle.
Exogenous L‐arginine attenuates the effects of angiotensin II on renal hemodynamics and the pressure natriuresis–diuresis relationship
Authors: Das Satarupa , Mattson David L 
Published: January 2014

Summary

Administration of exogenous L‐arginine (L‐Arg) attenuates angiotensin‐II (AngII)‐mediated hypertension and kidney disease in rats.

The present study assessed renal hemodynamics and pressure diuresis–natriuresis in anaesthetized rats infused with vehicle, AngII (20 ng/kg per min i.v.) or AngII + L‐Arg (300 μg/kg per min i.v.). Experiments in isolated aortic rings were carried out to assess L‐Arg effects on the vasculature.

Increasing renal perfusion pressure (RPP) from ˜100 to 140 mmHg resulted in a nine‐ to tenfold increase in urine flow and sodium excretion rate in control animals. In comparison, AngII infusion significantly reduced renal blood flow (RBF) and glomerular filtration rate (GFR) by 40–42%, and blunted the pressure‐dependent increase in urine flow and sodium excretion rate by 54–58% at elevated RPP. Supplementation of L‐Arg reversed the vasoconstrictor effects of AngII and restored pressure‐dependent diuresis to levels not significantly different from control rats.

Dose‐dependent contraction to AngII (10−10 mol/L to 10−7 mol/L) was observed with a maximal force equal to 27 ± 3% of the response to 10−5 mol/L phenylephrine. Contraction to 10−7 mol/L AngII was blunted by 75 ± 3% with 10−4 mol/L L‐Arg. The influence of L‐Arg to blunt AngII‐mediated contraction was eliminated by endothelial denudation or incubation with nitric oxide synthase inhibitors. Furthermore, the addition of 10−3 mol/L cationic or neutral amino acids, which compete with L‐Arg for cellular uptake, blocked the effect of L‐Arg. Anionic amino acids did not influence the effects of L‐Arg on AngII‐mediated contraction.

These studies show that L‐Arg blunts AngII‐mediated vascular contraction by an endothelial‐ and nitric oxide synthase‐dependent mechanism involving cellular uptake of L‐Arg.
Confucius institutes (Respond to this article at http://www.therai.org.uk/at/debate)
Authors: Sahlins Marshall , Turk James L. 
Published: January 2014

Many hundreds Confucius Institutes have mushroomed in higher education centres all over the world. In this comment, Marshall Sahlins continues his analysis of troublesome aspects of these institutions and considers what anthropologists have come up with in terms of research on these so far. He also touches on the Canadian campaign for university teachers to boycott these.James Turk commends Marshall Sahlins for looking into the issue of academic freedom in relation to Confucius Institutes. This is part of a campaign by the Canadian Association of University Teachers to secure academic freedom where universities enter into collaboration with third parties.
What do popular Spanish women's magazines say about caesarean section? A 21‐year survey
Authors: Torloni MR , Campos Mansilla B , Merialdi M , Betrán AP 
Published: January 2014

ObjectivesCaesarean section (CS) rates are increasing worldwide and maternal request is cited as one of the main reasons for this trend. Women's preferences for route of delivery are influenced by popular media, including magazines. We assessed the information on CS presented in Spanish women's magazines.DesignSystematic review.SettingWomen's magazines printed from 1989 to 2009 with the largest national distribution.SampleArticles with any information on CS.MethodsArticles were selected, read and abstracted in duplicate. Sources of information, scientific accuracy, comprehensiveness and women's testimonials were objectively extracted using a content analysis form designed for this study.Main outcome measuresAccuracy, comprehensiveness and sources of information.ResultsMost (67%) of the 1223 selected articles presented exclusively personal opinion/birth stories, 12% reported the potential benefits of CS, 26% mentioned the short‐term and 10% mentioned the long‐term maternal risks, and 6% highlighted the perinatal risks of CS. The most frequent short‐term risks were the increased time for maternal recovery (n = 86), frustration/feelings of failure (n = 83) and increased post‐surgical pain (n = 71). The most frequently cited long‐term risks were uterine rupture (n = 57) and the need for another CS in any subsequent pregnancy (n = 42). Less than 5% of the selected articles reported that CS could increase the risks of infection (n = 53), haemorrhage (n = 31) or placenta praevia/accreta in future pregnancies (n = 6). The sources of information were not reported by 68% of the articles.ConclusionsThe portrayal of CS in Spanish women's magazines is not sufficiently comprehensive and does not provide adequate important information to help the readership to understand the real benefits and risks of this route of delivery.
In Vitro Anti‐Inflammatory Activity of Selected Oxalate‐Degrading Probiotic Bacteria: Potential Applications in the Prevention and Treatment of Hyperoxaluria
Authors: Giardina Silvana , Scilironi Cristina , Michelotti Angela , Samuele Alberta , Borella Fabio , Daglia Maria , Marzatico Fulvio 
Published: January 2014

AbstractOxalate (Ox) is a very common component of the human diet, capable to collect in the renal tissue and bind calcium to form calcium oxalate (CaOx) crystals. A supersaturation of CaOx crystal may cause nephrocalcinosis and nephrolithiasis. The inflammation derived from the CaOx crystal accumulation, together with innate or secondary renal alterations, could strongly affect the renal function. In this case a consumption of probiotics with either oxalate‐degrading activity at intestinal level and systemic anti‐inflammatory activity could be an alternative approach to treat the subjects with excess of urinary oxalate excretion. 11 strains of lactic acid bacteria (Lactobacilli and Bifidobacteria), already included in the list of bacteria safe for the human use, were investigated for their capability to degrade oxalate by mean of RP‐HPLC‐UV method and modulate inflammation in an in vitro model system based on peripheral blood mononuclear cells. Four promising bacterial strains (Lactobacillus plantarum PBS067, Lactobacillus acidophilus LA‐14, Bifidobacterium breve PBS077, Bifidobacterium longum PBS078) were identified as innovative biological tools for the prevention and the therapeutic treatment of hyperoxaluria and the inflammatory events associated to the Ox accumulation.Practical ApplicationThe oxalate‐degrading activity of some probiotics and their capability to modulate the release of inflammation mediators could be exploited as a new nutraceutical and therapeutic approach for the treatment of oxalate accumulation and the related inflammatory state.
Initiation of the flexirubin biosynthesis in Chitinophaga pinensis
Authors: Schöner Tim A. , Fuchs Sebastian W. , Schönau Christian , Bode Helge B. 
Published: January 2014

SummaryBacteria from the Bacteroidetes phylum are known producers of the chemotaxonomic relevant flexirubins. These orange pigments comprise a non‐isoprenoid aryl‐polyene carboxylic acid esterified with a dialkylresorcinol. Herein, we report a gene cluster from Chitinophaga pinensis encoding the biosynthesis of the polyene moiety and the biochemical characterization of a tyrosine ammonia‐lyase and a 4‐coumarate‐CoA ligase responsible for the initiation of the polyene biosynthesis. Additionally, the flexirubin of C. pinensis was characterized by a combination of feeding experiments, high‐performance liquid chromatography tandem mass spectrometry and matrix‐assisted laser desorption/ionization mass spectrometry.