bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intra‐genomic variation in G + C content and its implications for DNA stable isotope probing
Authors: Youngblut Nicholas D. , Buckley Daniel H. 
Published: August 2014

SummaryCombining deoxyribonucleic acid (DNA‐based) stable isotope probing (DNA‐SIP) with high‐throughput sequencing provides a powerful culture‐independent means to link microbial metabolic function to genomic information and taxonomic identity. DNA buoyant density (BD) in isopycnic gradients is dependent on both isotope incorporation and G + C content. G + C content varies across a genome but is constrained at rrn operons; hence, the ability to resolve isotopically labelled DNA from unlabelled DNA in SIP may vary between small subunit‐ribosomal nucleic acid (SSU rRNA) amplicon and shotgun‐read sequencing applications. We tested this hypothesis by evaluating the G + C content of genomic DNA fragments that encompassed either an SSU rRNA template (‘amplicon‐fragments’) or a shotgun read template (‘shotgun‐fragments’). We find that, contrary to expectations, the BD distribution of amplicon‐fragments is non‐normal and can be highly skewed. Furthermore, the BD distribution of amplicon‐fragments can differ substantially from that of shotgun‐fragments from the same genome. Our findings demonstrate the impact of G + C content on the downstream applications of DNA‐SIP, which will aid in proper experimental design and the development of statistical tests to accurately identify sequences derived from isotopically labelled DNA.
Transcriptional responses of the bacterial antagonist Serratia plymuthica to the fungal phytopathogen Rhizoctonia solani
Authors: Neupane Saraswoti , Finlay Roger D. , Alström Sadhna , Elfstrand Malin , Högberg Nils 
Published: August 2014

SummaryRhizobacteria with biocontrol ability exploit a range of mechanisms to compete successfully with other microorganisms and to ensure their growth and survival in the rhizosphere, ultimately promoting plant growth. The rhizobacterium Serratia plymuthica AS13 is able to promote oilseed rape growth and improve seedling survival in the presence of the fungal pathogen, Rhizoctonia solani AG 2‐1; however, our understanding of the mechanisms underlying the antagonism of Serratia is limited. To elucidate possible mechanisms, genome‐wide gene expression profiling of S. plymuthica AS13 was carried out in the presence or absence of R. solani. We used RNA sequencing methodology to obtain a comprehensive overview of Serratia gene expression in response to R. solani. The differential gene expression profiles of S. plymuthica AS13 revealed significantly increased expression of genes related to the biosynthesis of the antibiotic pyrrolnitrin (prnABCD), protease production and transporters. The results presented here provide evidence that antibiosis is a major functional mechanism underlying the antagonistic behaviour of S. plymuthica AS13.
A trans‐outer membrane porin‐cytochrome protein complex for extracellular electron transfer by Geobacter sulfurreducens PCA
Authors: Liu Yimo , Wang Zheming , Liu Juan , Levar Caleb , Edwards Marcus J. , Babauta Jerome T. , Kennedy David W. , Shi Zhi , Beyenal Haluk , Bond Daniel R. , Clarke Thomas A. , Butt Julea N. , Richardson David J. , Rosso Kevin M. , Zachara John M , Fredrickson James K. , Shi Liang 
Published: August 2014

SummaryThe multi‐heme, outer membrane c‐type cytochrome (c‐Cyt) OmcB of Geobacter sulfurreducens was previously proposed to mediate electron transfer across the outer membrane. However, the underlying mechanism has remained uncharacterized. In G. sulfurreducens, the omcB gene is part of two tandem four‐gene clusters, each is predicted to encode a transcriptional factor (OrfR/OrfS), a porin‐like outer membrane protein (OmbB/OmbC), a periplasmic c‐type cytochrome (OmaB/OmaC) and an outer membrane c‐Cyt (OmcB/OmcC) respectively. Here, we showed that OmbB/OmbC, OmaB/OmaC and OmcB/OmcC of G. sulfurreducens PCA formed the porin‐cytochrome (Pcc) protein complexes, which were involved in transferring electrons across the outer membrane. The isolated Pcc protein complexes reconstituted in proteoliposomes transferred electrons from reduced methyl viologen across the lipid bilayer of liposomes to Fe(III)‐citrate and ferrihydrite. The pcc clusters were found in all eight sequenced Geobacter and 11 other bacterial genomes from six different phyla, demonstrating a widespread distribution of Pcc protein complexes in phylogenetically diverse bacteria. Deletion of ombB‐omaB‐omcB‐orfS‐ombC‐omaC‐omcC gene clusters had no impact on the growth of G. sulfurreducens PCA with fumarate but diminished the ability of G. sulfurreducens PCA to reduce Fe(III)‐citrate and ferrihydrite. Complementation with the ombB‐omaB‐omcB gene cluster restored the ability of G. sulfurreducens PCA to reduce Fe(III)‐citrate and ferrihydrite.
Biology and epidemics of Candidatus Liberibacter species, psyllid‐transmitted plant‐pathogenic bacteria
Authors: Haapalainen M. 
Published: August 2014

AbstractCandidatus Liberibacter species are Gram‐negative bacteria that live as phloem‐limited obligate parasites in plants, and are associated with several plant diseases. These bacteria are transmitted by insects called psyllids, or jumping plant lice, which feed on plant phloem sap. Citrus huanglongbing (yellow shoot) or citrus greening disease is associated with three different species of Ca. Liberibacter – Ca. L. asiaticus, Ca. L. africanus and Ca. L. americanus – all originally found on different continents. Ca. L. asiaticus is the most severe pathogen, spread by Asian citrus psyllid Diaphorina citri and causing devastating epidemics in several countries. Ca. L. africanus occurs in Africa where it is spread by the African citrus psyllid Trioza erytreae. Ca. Liberibacter solanacearum is associated with diseases in several solanaceous plants, and transmitted by potato psyllid Bactericera cockerelli. Zebra chip disease is causing large damage in potato crops in North America. In Europe Ca. Liberibacter solanacearum is associated with diseases of the Apiaceae family of plants, carrot and celery, and transmitted by psyllids Trioza apicalis and Bactericera trigonica. When Ca. Liberibacter is suspected as the disease agent, the diagnosis is confirmed by DNA‐based detection methods. Ca. Liberibacter‐associated plant diseases can be controlled by using healthy plant propagation material, eradicating symptomatic plants, and by controlling the psyllid populations spreading the disease.
Patterns of change in implementation of state alcohol control policies in the United States, 1999–2011
Authors: Nelson Toben F. , Xuan Ziming , Blanchette Jason G. , Heeren Timothy C. , Naimi Timothy S. 
Published: August 2014

AbstractAimsTo examine state alcohol control policy implementation by policy efficacy and intent.DesignA descriptive longitudinal analysis of policy implementation.SettingThe United States, 1999–2011.ParticipantsFifty states and the District of Columbia.MeasurementsTwenty‐nine state‐level policies were rated based on an implementation rating (IR; range = 0.0–1.0) gathered from the Alcohol Policy Information System, government and industry reports and other sources; and expert judgment about policy efficacy for addressing binge drinking and alcohol‐impaired driving among the general population and youth, respectively.FindingsOn average, implementation of the most effective general population policies did not change [mean IR = 0.366 in 1999; 0.375 in 2011; slope for annual change = 0.001; 95% confidence interval (CI) for the slope −0.001, 0.002]. In contrast, implementation increased over time for less effective policies (mean IR = 0.287 in 1999; 0.427 in 2011; slope for annual change compared with most effective policies = 0.009; slope 95% CI = 0.002–0.007), for youth‐oriented policies (mean IR = 0.424 in 1999; 0.511 in 2011; slope for annual change compared with most effective policies = 0.007; slope 95% CI = 0.005–0.009), and for impaired driving policies (mean IR = 0.493 in 1999; 0.608 in 2011; slope for annual change compared with most effective policies = 0.0105; slope 95% CI = 0.007–0.014).ConclusionsImplementation of politically palatable state alcohol policies, such as those targeting youth and alcohol‐impaired driving, and less effective policies increased during 1999–2011 in the United States, while the most effective policies that may maximally protect public health remained underused.
Forecasting the breaching of the control threshold for Ceutorhynchus pallidactylus in oilseed rape
Authors: Eickermann Michael , Junk Jürgen , Hoffmann Lucien , Beyer Marco 
Published: August 2014

Abstract

The cabbage stem weevil Ceutorhynchus pallidactylus (Mrsh.) (Col.: Curculionidae) is a common pest in oilseed rape Brassica napus L. throughout Europe.
The abundance of the cabbage stem weevil was monitored in field surveys by using yellow water traps between 2007 and 2012 at five locations in Luxembourg. We forecast the abundance of the cabbage stem weevil at levels above the control threshold in oilseed rape in springtime.
If mean winter temperatures between 5 and 13 February are closer to 4.0 °C than to −2.4 °C, no breaching of the control threshold is to be expected in the subsequent March. The monitoring effort might be saved in those years.
Leave‐one‐out cross‐validation revealed that whether the control threshold was exceeded could be correctly predicted based on the observed temperature differences identified in 22 out of 27 cases (81.5%) in the present study.
The present approach can be easily transferred to regions where air temperature data are available, although it should not be used without prior local validation.
Epidermal growth factor receptor‐tyrosine kinase inhibitors in advanced squamous cell carcinoma of the lung: A meta‐analysis
Authors: Ameratunga Malaka , Pavlakis Nick , Gebski Val , Broad Adam , Khasraw Mustafa 
Published: August 2014

AbstractAimTyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) are well established in treating metastatic pulmonary adenocarcinoma, especially patients with activating EGFR mutations. EGFR mutations are rare in pulmonary squamous cell carcinomas (SCCs). There are conflicting data supporting the efficacy of EGFR‐TKIs in advanced lung SCC. We analyzed the impact of EGFR‐TKIs on progression‐free survival (PFS) and overall survival (OS) in unselected patients with lung SCC.MethodsWe searched for randomized controlled trials (RCTs) comparing EGFR‐TKIs alone with placebo in patients with metastatic non‐small cell lung cancer. RCTs in all settings (front line/maintenance/subsequent) were included. The primary outcome was OS in the SCC population. We used published hazard ratios (HRs), and when unavailable, unpublished data were sought. Pooled estimates of treatment effect on OS and PFS were calculated using the fixed‐effects inverse variance weighted method.ResultsEight eligible RCTs were included: 2 first‐line, 6 second‐line or beyond, evaluating 1781 patients. Data were available for OS in four studies (second‐line; N = 1420) and for PFS in four studies (3 second‐line, 1 first‐line; N = 788). EGFR‐TKIs significantly prolonged OS with a HR of 0.88 (95% confidence interval [CI] 0.78–1.00, P = 0.04), and significantly prolonged PFS with a HR of 0.77 (95% CI 0.65–0.92, P = 0.004).ConclusionEGFR mutations are rare in lung SCC. However, EGFR‐TKIs have a modest therapeutic effect compared to placebo in unselected patients with advanced pulmonary SCC, and can be considered in these patients. EGFR‐mutation‐independent mechanisms may explain efficacy of EGFR inhibitors in this setting.
Effect of diet‐ and lifestyle‐based metabolic risk‐modifying interventions on preeclampsia: a meta‐analysis
Authors: Allen Rebecca , Rogozinska Ewelina , Sivarajasingam Priya , Khan Khalid S. , Thangaratinam Shakila 
Published: August 2014

AbstractObjectiveTo evaluate the effect of dietary and lifestyle interventions with the potential to modify metabolic risk factors on the risk of preeclampsia.Data sourcesWe searched MEDLINE, EMBASE and Cochrane from inception until February 2013. Randomized trials in pregnant women evaluating the effect of dietary and lifestyle interventions with the potential to modify metabolic risks such as obesity, hyperlipidemia, hyperglycemia and hypertension on the risk of preeclampsia were included.Study selectionTwo independent reviewers selected studies, extracted data and assessed quality. Results were summarized as pooled relative risks (RR) for dichotomous data.ResultsEighteen studies (8712 women) met our search criteria for inclusion. Six studies evaluated diet (2695 women), six studied mixed interventions with diet, physical activity and lifestyle (1438 women) and six assessed essential fatty acid supplementation (4579 women). The interventions overall reduced the risk of preeclampsia (RR 0.81, 95% CI 0.69–0.94; p = 0.006 I2 = 0%) compared with the control group. Dietary interventions reduced the risk of preeclampsia by 33% (RR 0.67, 95% CI 0.53–0.85; p = 0.001; I2 = 0%). There was no reduction in the risk of preeclampsia with mixed interventions (RR 0.93, 95% CI 0.66–1.32, p = 0.68, I2 = 0%) or fatty acid supplementation (RR 0.92, 95% CI 0.71–1.18; p = 0.49, I2 = 15%). Meta‐regression showed a borderline impact of gestational diabetes status (p = 0.05) on the observed effect.ConclusionDietary and lifestyle interventions have the potential to reduce the risk of preeclampsia. The effect of additional therapeutic interventions in women with gestational diabetes mellitus on preeclampsia is not known.
Balance of antiangiogenic and angiogenic factors in the context of the etiology of preeclampsia
Authors: Seki Hiroyuki 
Published: August 2014

AbstractThe “two‐stage disorder” theory that is assumed for the etiology of preeclampsia hypothesizes that antiangiogenic and angiogenic factors and/or placental debris play an important role in this disorder. The physiological actions of placental debris occur via the balance between antiangiogenic and angiogenic factors. Accordingly, this balance between antiangiogenic and angiogenic factors should be investigated to elucidate the various pathological features of preeclampsia. Their accurate evaluation is needed to investigate not only antiangiogenic factors (such as sFlt‐1 and sEng) and angiogenic factors (such as vascular endothelial growth factor, placental growth factor and transforming growth factor‐β) but also the expression level of their receptors such as Flt‐1 and Eng. However, it is ethically and technically difficult to investigate the above‐mentioned factors at antepartum in human patients. The examination of the ratios of sFlt‐1/vascular endothelial growth factor receptor ligands and sEng/transforming vascular endothelial growth factor‐β and the use of experimental animal models may help in elucidating various unresolved issues in preeclampsia.
CD30 expression in de novo diffuse large B‐cell lymphoma: a population‐based study from British Columbia
Authors: Slack Graham W. , Steidl Christian , Sehn Laurie H. , Gascoyne Randy D. 
Published: August 2014

SummaryDiffuse large B‐cell lymphoma (DLBCL) is a heterogeneous disease with variable therapeutic responses and alternative therapies are needed for patients with unfavourable treatment outcomes after standard treatment with R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). One promising candidate is brentuximab vedotin, an antibody‐drug conjugate targeting CD30‐expressing cells. However, CD30 (TNFRSF8) expression patterns in DLBCL are not well described thus far. Here, we examined CD30 expression in a population‐based cohort of immunocompetent patients from British Columbia with de novo DLBCL using immunohistochemistry. 385 cases of formalin‐fixed paraffin‐embedded DLBCL in tissue microarrays were evaluated. 95 cases (25%) harboured CD30+ tumour cells. Using a > 0% cut‐off, CD30 expression was predictive of superior 5‐year progression‐free survival within R‐CHOP treated germinal centre B‐cell‐like (GCB) DLBCL (86% vs. 64%, P = 0·020), which was independent of the International Prognostic Index. Epstein‐Barr virus (EBV) was identified in 11 (3%) cases, all of which were non‐GCB (P = 0·001) and almost exclusively positive for CD30 expression (10/11) (P < 0·001). We conclude CD30 is expressed in a substantial proportion of DLBCL and CD30 immunohistochemistry may be a useful prognostic marker in R‐CHOP treated GCB‐DLBCL. The significant association of CD30 with EBV‐positive non‐GCB DLBCL suggests a distinct pathobiology for these cases.
DNA demethylation and invasive cancer: implications for therapeutics
Authors: Cheishvili David , Boureau Lisa , Szyf Moshe 
Published: August 2014

One of the hallmarks of cancer is aberrant DNA methylation, which is associated with abnormal gene expression. Both hypermethylation and silencing of tumour suppressor genes as well as hypomethylation and activation of prometastatic genes are characteristic of cancer cells. As DNA methylation is reversible, DNA methylation inhibitors were tested as anticancer drugs with the idea that such agents would demethylate and reactivate tumour suppressor genes. Two cytosine analogues, 5‐azacytidine (Vidaza) and 5‐aza‐2′‐deoxycytidine, were approved by the Food and Drug Administration as antitumour agents in 2004 and 2006 respectively. However, these agents might cause activation of a panel of prometastatic genes in addition to activating tumour suppressor genes, which might lead to increased metastasis. This poses the challenge of how to target tumour suppressor genes and block cancer growth with DNA‐demethylating drugs while avoiding the activation of prometastatic genes and precluding the morbidity of cancer metastasis. This paper reviews current progress in using DNA methylation inhibitors in cancer therapy and the potential promise and challenges ahead.Linked ArticlesThis article is part of a themed section on Epigenetics and Therapy. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue‐11
The ceramide kinase inhibitor NVP‐231 inhibits breast and lung cancer cell proliferation by inducing M phase arrest and subsequent cell death
Authors: Pastukhov Oleksandr , Schwalm Stephanie , Zangemeister‐Wittke Uwe , Fabbro Doriano , Bornancin Frederic , Japtok Lukasz , Kleuser Burkhard , Pfeilschifter Josef , Huwiler Andrea 
Published: August 2014

Background and PurposeCeramide kinase (CerK) catalyzes the generation of ceramide‐1‐phosphate which may regulate various cellular functions, including inflammatory reactions and cell growth. Here, we studied the effect of a recently developed CerK inhibitor, NVP‐231, on cancer cell proliferation and viability and investigated the role of cell cycle regulators implicated in these responses.Experimental ApproachThe breast and lung cancer cell lines MCF‐7 and NCI‐H358 were treated with increasing concentrations of NVP‐231 and DNA synthesis, colony formation and cell death were determined. Flow cytometry was performed to analyse cell cycle distribution of cells and Western blot analysis was used to detect changes in cell cycle regulator expression and activation.Key ResultsIn both cell lines, NVP‐231 concentration‐dependently reduced cell viability, DNA synthesis and colony formation. Moreover it induced apoptosis, as measured by increased DNA fragmentation and caspase‐3 and caspase‐9 cleavage. Cell cycle analysis revealed that NVP‐231 decreased the number of cells in S phase and induced M phase arrest with an increased mitotic index, as determined by increased histone H3 phosphorylation. The effect on the cell cycle was even more pronounced when NVP‐231 treatment was combined with staurosporine. Finally, overexpression of CerK protected, whereas down‐regulation of CerK with siRNA sensitized, cells for staurosporine‐induced apoptosis.Conclusions and ImplicationsOur data demonstrate for the first time a crucial role for CerK in the M phase control in cancer cells and suggest its targeted inhibition, using drugs such as NVP‐231, in combination with conventional pro‐apoptotic chemotherapy.
Management of hypertension and heart failure in patients with Addison's disease
Authors: Inder Warrick J. , Meyer Caroline , Hunt Penny J. 
Published: August 2014

SummaryAddison's disease may be complicated by hypertension and less commonly by heart failure. We review the pathophysiology of the renin‐angiotensin‐aldosterone axis in Addison's disease and how this is altered in the setting of hypertension and heart failure. An essential first step in management in both conditions is optimizing glucocorticoid replacement and considering dose reduction if excessive. Following this, if a patient with Addison's disease remains hypertensive, the fludrocortisone dose should be reviewed and reduced if there are clinical and/or biochemical signs of mineralocorticoid excess. In the absence of such signs, where the renin is towards the upper end of the normal range or elevated, an angiotensin II (AII) receptor antagonist or angiotensin converting enzyme (ACE) inhibitor is the treatment of choice, and the fludrocortisone dose should remain unchanged. Dihydropyridine calcium channel blockers are clinically useful as second line agents, but diuretics should be avoided. In the setting of heart failure, there is an increase in total body sodium and water; therefore, it is appropriate to reduce and rarely consider ceasing the fludrocortisone. Loop diuretics may be used, but not aldosterone antagonists such as spironolactone or eplerenone. Standard treatment with ACE inhibitors, or as an alternative, AII receptor antagonists, are appropriate. Measurements of renin are no longer helpful in heart failure to determine the volume status but plasma levels of brain natriuretic peptide (BNP/proBNP) may help guide therapy.