bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Host Species on Topography of the Fitness Landscape for a Plant RNA Virus
Authors: Cervera Héctor , Lalić Jasna , Elena Santiago F. 
Published: September 2016

ABSTRACT

Adaptive fitness landscapes are a fundamental concept in evolutionary biology that relate the genotypes of individuals to their fitness. In the end, the evolutionary fate of evolving populations depends on the topography of the landscape, that is, the numbers of accessible mutational pathways and possible fitness peaks (i.e., adaptive solutions). For a long time, fitness landscapes were only theoretical constructions due to a lack of precise information on the mapping between genotypes and phenotypes. In recent years, however, efforts have been devoted to characterizing the properties of empirical fitness landscapes for individual proteins or for microbes adapting to artificial environments. In a previous study, we characterized the properties of the empirical fitness landscape defined by the first five mutations fixed during adaptation of tobacco etch potyvirus (TEV) to a new experimental host,
Arabidopsis thaliana
. Here we evaluate the topography of this landscape in the ancestral host
Nicotiana tabacum
. By comparing the topographies of the landscapes for the two hosts, we found that some features remained similar, such as the existence of fitness holes and the prevalence of epistasis, including cases of sign and reciprocal sign epistasis that created rugged, uncorrelated, and highly random topographies. However, we also observed significant differences in the fine-grained details between the two landscapes due to changes in the fitness and epistatic interactions of some genotypes. Our results support the idea that not only fitness tradeoffs between hosts but also topographical incongruences among fitness landscapes in alternative hosts may contribute to virus specialization.

IMPORTANCE
Despite its importance for understanding virus evolutionary dynamics, very little is known about the topography of virus adaptive fitness landscapes, and even less is known about the effects that different host species and environmental conditions may have on this topography. To bridge this gap, we evaluated the topography of a small fitness landscape formed by all genotypes that result from every possible combination of the first five mutations fixed during adaptation of TEV to the novel host
A. thaliana
. To assess the effect that host species may have on this topography, we evaluated the fitness of every genotype in both the ancestral and novel hosts. We found that both landscapes share some macroscopic properties, such as the existence of holes and being highly rugged and uncorrelated, yet they differ in microscopic details due to changes in the magnitude and sign of fitness and epistatic effects.
New Insights into the Formation of Viable but Nonculturable Escherichia coli O157:H7 Induced by High-Pressure CO
2
Authors: Zhao Feng , Wang Yongtao , An Haoran , Hao Yanling , Hu Xiaosong , Liao Xiaojun 
Published: August 2016

ABSTRACT

The formation of viable but nonculturable (VBNC)
Escherichia coli
O157:H7 induced by high-pressure CO
2
(HPCD) was investigated using RNA sequencing (RNA-Seq) transcriptomics and isobaric tag for relative and absolute quantitation (iTRAQ) proteomic methods. The analyses revealed that 97 genes and 56 proteins were significantly changed upon VBNC state entry. Genes and proteins related to membrane transport, central metabolisms, DNA replication, and cell division were mainly downregulated in the VBNC cells. This caused low metabolic activity concurrently with a division arrest in cells, which may be related to VBNC state formation. Cell division repression and outer membrane overexpression were confirmed to be involved in VBNC state formation by homologous expression of
z2046
coding for transcriptional repressor and
ompF
encoding outer membrane protein F. Upon VBNC state entry, pyruvate catabolism in the cells shifted from the tricarboxylic acid (TCA) cycle toward the fermentative route; this led to a low level of ATP. Combating the low energy supply, ATP production in the VBNC cells was compensated by the degradation of
l
-serine and
l
-threonine, the increased AMP generation, and the enhanced electron transfer. Furthermore, tolerance of the cells with respect to HPCD-induced acid, oxidation, and high CO
2
stresses was enhanced by promoting the production of ammonia and NADPH and by reducing CO
2
production during VBNC state formation. Most genes and proteins related to pathogenicity were downregulated in the VBNC cells. This would decrease the cell pathogenicity, which was confirmed by adhesion assays. In conclusion, the decreased metabolic activity, repressed cell division, and enhanced survival ability in
E. coli
O157:H7 might cause HPCD-induced VBNC state formation.

IMPORTANCE
Escherichia coli
O157:H7 has been implicated in large foodborne outbreaks worldwide. It has been reported that the presence of as few as 10 cells in food could cause illness. However, the presence of only 0.73 to 1.5 culturable
E. coli
O157:H7 cells in salted salmon roe caused infection in Japan. Investigators found that
E. coli
O157:H7 in the viable but nonculturable (VBNC) state was the source of the outbreak. So far, formation mechanisms of VBNC state are not well known. In a previous study, we demonstrated that high-pressure CO
2
(HPCD) could induce the transition of
E. coli
O157:H7 into the VBNC state. In this study, we used RNA-Seq transcriptomic analysis combined with the iTRAQ proteomic method to investigate the formation of VBNC
E. coli
O157:H7 induced by HPCD treatment. Finally, we proposed a putative formation mechanism of the VBNC cells induced by HPCD, which may provide a theoretical foundation for controlling the VBNC state entry induced by HPCD treatment.
Wyoming on the run—Toward final Paleoproterozoic assembly of Laurentia
Authors: Kilian Taylor M. , Chamberlain Kevin R. , Evans David A.D. , Bleeker Wouter , Cousens Brian L. 
Published: September 2016

Abstract
Paleoproterozoic suture zones mark the formation of supercontinent Nuna and provide a record of North America’s assembly. Conspicuously young ages (ca. 1.715 Ga) associated with deformation in southeast Wyoming craton argue for a more protracted consolidation of Laurentia, long after peak metamorphism in the Trans-Hudson orogen. Using paleomagnetic data from the newly dated 1899 ± 5 Ma Sourdough mafic dike swarm (Wyoming craton), we compare the relative positions of Wyoming, Superior, and Slave cratons before, during, and after peak metamorphism in the Trans-Hudson orogen. With these constraints, we refine a collisional model for Laurentia that incorporates Wyoming craton after Superior and Slave cratons united, redefining the Paleoproterozoic sutures that bind southern Laurentia.
The origin of Earth’s first continents and the onset of plate tectonics
Authors: Hastie Alan R. , Fitton J. Godfrey , Bromiley Geoffrey D. , Butler Ian B. , Odling Nicholas W.A. 
Published: September 2016

Abstract
The growth and recycling of continental crust has resulted in the chemical and thermal modification of Earth’s mantle, hydrosphere, atmosphere, and biosphere for ∼4.0 b.y. However, knowledge of the protolith that gave rise to the first continents and whether the environment of formation was a subduction zone still remains unknown. Here, tonalite melts are formed in high P-T experiments in which primitive oceanic plateau starting material is used as an analogue for Eoarchean (3.6–4.0 Ga) oceanic crust generated at early spreading centers. The tonalites are produced at 1.6–2.2 GPa and 900–950 °C and are mixed with slab-derived aqueous fluids to generate melts that have compositions identical to that of Eoarchean continental crust. Our data support the idea that the first continents formed at ca. 4 Ga and subsequently, through the subduction and partial melting of ∼30–45-km-thick Eoarchean oceanic crust, modified Earth’s mantle and Eoarchean environments and ecosystems.
Criticality in the planform behavior of the Ganges River meanders
Authors: Carling P.A. , Gupta N. , Atkinson P.M. , He Huang Qing 
Published: September 2016

Abstract
The critical point of planform transition from straight to meandering in the wandering Ganges River is identifiable. Recent remote-sensing data indicate that four similar meanders cut off, or attempted to cut off, after ∼31–35 yr, primarily due to channel aggradation. As main channels aggrade, sinuosity is maximized for broad channel widths and small radii of curvature and relaxes for bends of greater radii. Maximized form resistance occurs close to self-organized criticality and promotes cutoffs. Avulsions lead to main channel narrowing and prevent further bend tightening, relaxing the system by reducing sinuosity. Thus, the wandering river oscillates in space and time across the transition from a more ordered to a more chaotic state. Planform behavior is described by the Jerolmack-Mohrig mobility number and the Parker stability criterion, which well define meanders behavior as they approach criticality and then relax via partial or completed avulsions. The results have significance for river engineering and river network and stratigraphic modeling. Such an approach could be of practical value when predicting the behaviors of other major wandering rivers.
Plasma glucose and insulin response to two oral nutrition supplements in adults with type 2 diabetes mellitus
Authors: Huhmann Maureen B , Smith Kristen N , Schwartz Sherwyn L , Haller Stacie K , Irvin Sarah , Cohen Sarah S 
Published: September 2016

ObjectiveThe purpose of this clinical trial was to compare the glucose usage of two oral nutritional supplement (ONS) products and to assess whether a diabetes-specific formulation provides improved glucose stabilization and management compared with a standard formula.Research design and methodsA total of 12 subjects with type 2 diabetes (7 males and 5 females) completed a randomized, cross-over design trial. Each subject consumed isocaloric amounts of either the standard ONS or the diabetes-specific formula ONS on different dates, 1 week apart. Glucose and insulin measures were recorded at baseline, and 10, 20, 30, 60, 90, 120, 150, 180, 210 and 240 min after the beverage was consumed and then used to calculate area under the curve (AUC) for each subject.ResultsThe mean glucose AUC was lower in the diabetes-specific ONS group than in the standard group (p<0.0001), but there was not a significant difference observed for mean insulin AUC (p=0.068). A sensitivity analysis of the mean insulin AUC measures was performed by removing a potential outlier from the analysis, and this resulted in a significant difference between the groups (p=0.012). First-phase insulin measures and an insulinogenic index calculated for the beverages showed no significant differences.ConclusionsOn the basis of the results of this trial of 12 subjects, the diabetes-specific ONS appears to provide better glucose maintenance in persons with type 2 diabetes when compared to the standard formula ONS.Trial registration numberNCT02612675.
Characteristics, treatment and in-hospital outcomes of patients with STEMI in a metropolitan area of a developing country: an initial report of the extended Jakarta Acute Coronary Syndrome registry
Authors: Dharma Surya , Andriantoro Hananto , Purnawan Ismi , Dakota Iwan , Basalamah Faris , Hartono Beny , Rasmin Ronaly , Isnanijah Herawati , Yamin Muhammad , Wijaya Ika Prasetya , Pratama Vireza , Gunawan Tjatur Bagus , Juwana Yahya Berkahanto , Suling Frits R W , Witjaksono A M Onny , Lasanudin Hengkie F , Iskandarsyah Kurniawan , Priatna Hardja , Tedjasukmana Pradana , Wahyumandradi Uki , Kosasih Adrianus , Budhiarti Imelda A , Pribadi Wisnoe , Wirianta Jeffrey , Lubiantoro Utojo , Pramesti Rini , Widowati Diah Retno , Aminda Sissy Kartini , Basalamah M Abas , Rao Sunil V 
Published: September 2016

ObjectiveWe studied the characteristics of patients with ST segment elevation myocardial infarction (STEMI) after expansion of a STEMI registry as part of the STEMI network programme in a metropolitan city and the surrounding area covering ∼26 million inhabitants.DesignRetrospective cohort study.SettingEmergency department of 56 health centres.Participants3015 patients with acute coronary syndrome, of which 1024 patients had STEMI.Main outcome measureCharacteristics of reperfusion therapy.ResultsThe majority of patients with STEMI (81%; N=826) were admitted to six academic percutaneous coronary intervention (PCI) centres. PCI centres received patients predominantly (56%; N=514) from a transfer process. The proportion of patients receiving acute reperfusion therapy was higher than non-reperfused patients (54% vs 46%, p<0.001), and primary PCI was the most common method of reperfusion (86%). The mean door-to-device (DTD) time was 102±68 min. In-hospital mortality of non-reperfused patients was higher than patients receiving primary PCI or fibrinolytic therapy (9.1% vs 3.2% vs 3.8%, p<0.001). Compared with non-academic PCI centres, patients with STEMI admitted to academic PCI centres who underwent primary PCI had shorter mean DTD time (96±44 min vs 140±151 min, p<0.001), higher use of manual thrombectomy (60.2% vs13.8%, p<0.001) and drug-eluting stent implantation (87% vs 69%, p=0.001), but had similar use of radial approach and intra-aortic balloon pump (55.7% vs 67.2%, and 2.2% vs 3.4%, respectively). In patients transferred for primary PCI, TIMI risk score ≥4 on presentation was associated with a prolonged door-in to door-out (DI-DO) time (adjusted OR 2.08; 95% CI 1.09 to 3.95, p=0.02).ConclusionsIn the expanded JAC registry, a higher proportion of patients with STEMI received reperfusion therapy, but 46% still did not. In developing countries, focusing the prehospital care in the network should be a major focus of care to improve the DI-DO time along with improvement of DTD time at PCI centres.Trial registration numberNCT02319473.
Community paediatric respiratory infection surveillance study protocol: a feasibility, prospective inception cohort study
Authors: Anderson Emma C , Ingle Suzanne Marie , Muir Peter , Beck Charles , Finn Adam , Leeming John Peter , Cabral Christie , Kesten Joanna May , Hay Alastair D 
Published: September 2016

IntroductionPaediatric respiratory tract infections (RTIs) are common reasons for primary care consultations and antibiotic prescribing. Locally relevant syndromic and microbiological surveillance information has the potential to improve the care of children with RTIs by normalising illness (parents) and reducing uncertainty (clinicians). Currently, most RTI studies are conducted at the point of healthcare service consultation, leaving the community burden, microbiology, symptom duration and proportion consulting largely unknown. This study seeks to establish the feasibility of (mainly online) participant recruitment and retention, and the acceptability/comparability of parent versus nurse-collected microbiological sampling, to inform the design of a future surveillance intervention study. Evidence regarding consultation rates and symptom duration is also sought.Methods and analysisA community-based, feasibility prospective inception cohort study, recruiting children aged ≥3 months and <16 years and their parents via general practitioner surgery invitation letter, aiming to collect data on 300 incident RTIs by July 2016. Following informed consent, parents provide baseline (demographic) data online, and respond to weekly emails to confirm the absence/presence of new RTI symptoms. Once symptomatic, parents provide daily data online (RTI symptoms, school/day-care attendance, time off work, health service use, medication), and a research nurse visits to collect clinical examination data and microbiological (nasal and saliva) swabs. Parents are invited to provide symptomatic (at nurse visit, but without nurse assistance) and asymptomatic (alone) swabs on recovery. A review of primary care medical notes will gather medical history, health service utilisation, referral and antibiotic prescribing rates. Feasibility will be assessed using recruitment and retention rates, data completeness; and acceptability by quantitative survey and qualitative interviews. Symptomatic parent and nurse swab pairs will be compared for microbe isolation.
Too hot to handle?
Authors: Campbell Madeleine 
Published: September 2016

THIS series gives readers the opportunity to consider and contribute to discussion of some of the ethical dilemmas that can arise in veterinary practice. Each month, a case scenario is presented, followed by discussion of some of the issues involved.In addition, a possible way forward is suggested; however, there is rarely a cut‐and‐dried answer in such cases, and readers may wish to suggest an alternative approach. This month's dilemma, ‘Too hot to handle?’, was submitted and is discussed by Madeleine Campbell. Readers with comments to contribute are invited to send them as soon as possible, so that they can be considered for publication in the next issue. Discussion of the dilemma ‘A request for euthanasia: handling the client’, which was published in the July/August issue of In Practice, appears on page 415.The series is being coordinated by Steven McCulloch, a practising vet with a PhD in the ethics of veterinary policy. It is hoped it will provide a framework that will help practitioners find solutions when facing similar dilemmas.
Fault reactivation in travertine and its impact on hydraulic transmissibility: laboratory experiments and mesoscale structures
Authors: Giwelli A. , Esteban L. , Delle Piane C. , Clennell M. B. 
Published: September 2016

Direct shear experiments were undertaken to investigate the effect of faulting and reactivation on the hydromechanical characteristics of faults in continental carbonate samples. The tested rock is a travertine of continental, microbial origin with a calcite content of 99 wt%, with a strongly laminated texture. Analyses of the intact and sheared samples performed using medical X-ray computed tomography (CT) revealed that the porosity is mainly composed of subplanar pores and vugs. Permeability is high along the laminations, controlled by interconnected pores and fractures. The travertine is a lithological analogue for Aptian pre-salt oil reservoir rocks found in South Atlantic offshore basins. Three samples, with dimensions of 240 × 110 × 150 mm, were sheared to a maximum displacement of 120 mm under different levels of effective vertical stress (6–45 MPa), resulting in the formation of cataclastic fault gouge surrounded by a dense fracture network. A new experimental method was used to reactivate the artificially formed fault by performing cyclic vertical loading at different shear displacements on a previously sheared sample, while keeping a constant pore-pressure differential throughout the test.
Pore-fluid responses across the fault zone were monitored continuously during both deformation (dynamic transmissibility) and hold periods (static transmissibility). Results show that the transmissibility reduces in all the samples for all values of the applied effective vertical stress and during shear reversal. The static transmissibility also decreases over time, which may be a result of creep deformation or the blocking of pore channels with gouge material. Our results indicate that once the gouge material is developed in the core of a carbonate fault zone, the dynamic transmissibility across that fault is permanently decreased, with little dependence on subsequent kinematics of reactivation, or changes in stress, so long as the gouge zone is not breached by a new structure.
Alteration and submergence of basalts in Kachchh, Gujarat, India: implications for the role of the Deccan Traps in the India–Seychelles break-up
Authors: Mitra Souvik , Mitra Kaushik , Gupta Saibal , Bhattacharya Satadru , Chauhan Prakash , Jain Nirmala 
Published: September 2016

Abstract

The Deccan Trap flood basalt volcanism has commonly been considered to have initiated the break-up of India from the Seychelles (
c.
62.5 Ma). In Kachchh, Gujarat, western India, the sedimentary succession in the Paleocene Matanomadh Formation was deposited on highly weathered Deccan Trap basalts that were altered to kaolinite before basin formation. This contrasts with the weathering pattern on flat-topped hills of the Deccan Traps outside the Cenozoic rift basins in the Kachchh region and other parts of India, where basalt is dominantly altered to smectitic minerals. As basalts that are altered to smectite and kaolinite occur just across the faults that bound the Matanomadh Basin, the differential weathering cannot be attributed to climate. Geochemical modelling shows that kaolinite stabilizes in preference to smectite if CO
2
- and O
2
-buffered rainwater interacts with well-drained basaltic rock at high water:rock ratios. Such conditions can be accomplished by rainfall on a slope created by Cenozoic rifting that exposes the graben flank and basin floor basalts to continuously flowing water, the composition of which is buffered by equilibration with the atmosphere. As the rift post-dates both the eruption of the basalts and subsequent smectite formation, the associated extensional tectonics must be unrelated to flood basalt volcanism, and is most likely to correspond to the India–Seychelles break-up.
Essential Role of DNA Methyltransferase 1–mediated Transcription of Insulin-like Growth Factor 2 in Resistance to Histone Deacetylase Inhibitors
Authors: Min Hye-Young , Lee Su-Chan , Woo Jong Kyu , Jung Hyun Jin , Park Kwan Hee , Jeong Hae Min , Hyun Seung Yeob , Cho Jaebeom , Lee Wooin , Park Ji Eun , Kwon So Jung , Lee Hyo-Jong , Ni Xiao , Shin Young Kee , Johnson Faye M. , Duvic Madeleine , Lee Ho-Young 
Published: September 2016

Abstract
Purpose: Histone deacetylase inhibitors (HDI) are promising anticancer therapies; however, drug resistance limits their efficacy. Here, we investigated the molecular mechanisms underlying HDI resistance, focusing on the mechanism of HDI-mediated induction of insulin-like growth factor 2 (IGF2) based on our previous study.
Experimental Design: The methylation status of CCCTC-binding factor (CTCF)-binding sites in the IGF2/H19 imprinting control region (ICR) were determined by methylation-specific PCR and bisulfite sequencing. The effectiveness of single or combinatorial blockade of DNA methyltransferase 1 (DNMT1) and histone deacetylase (HDAC) was evaluated using cell viability assay and patient-derived tumor xenograft (PDX) model.
Results: HDAC inhibition by vorinostat increased acetylated STAT3 (K685), resulting in transcriptional upregulation of DNMT1. DNMT1-mediated hypermethylation of CTCF-binding sites in the IGF2/H19 ICR decreased CTCF insulator activity, leading to a transcriptional upregulation of IGF2 and activation of the insulin-like growth factor 1 receptor (IGF-1R) pathway in cells with acquired or de novo vorinostat resistance. Strategies targeting DNMT1 diminished the IGF2 expression and potentiated vorinostat sensitivity in preclinical models of lung cancer with hypermethylation in the H19/IGF2 ICR. The degree of ICR hypermethylation correlated with vorinostat resistance in patient-derived lung tumors and in patients with hematologic malignancies.
Conclusions: DNMT1-mediated transcriptional upregulation of IGF2 is a novel mechanism of resistance to HDIs, highlighting the role of epigenetic deregulation of IGF2 in HDI resistance and the potential value of the H19/IGF2 ICR hypermethylation and DNMT1 expression as predictive biomarkers in HDI-based anticancer therapies. Clin Cancer Res; 23(5); 1299–311. ©2016 AACR.