bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomic and Transcriptomic Analyses of “CandidatusPelagibacter ubique” Describe the First PII-Independent Response to Nitrogen Limitation in a Free-Living Alphaproteobacterium
Authors: Smith Daniel P. , Thrash J. Cameron , Nicora Carrie D. , Lipton Mary S. , Burnum-Johnson Kristin E. , Carini Paul , Smith Richard D. , Giovannoni Stephen J. 
Published: November 2013

ABSTRACTNitrogen is one of the major nutrients limiting microbial productivity in the ocean, and as a result, most marine microorganisms have evolved systems for responding to nitrogen stress. The highly abundant alphaproteobacterium “CandidatusPelagibacter ubique,” a cultured member of the orderPelagibacterales(SAR11), lacks the canonical GlnB, GlnD, GlnK, and NtrB/NtrC genes for regulating nitrogen assimilation, raising questions about how these organisms respond to nitrogen limitation. A survey of 266Alphaproteobacteriagenomes found these five regulatory genes nearly universally conserved, absent only in intracellular parasites and members of the orderPelagibacterales, including “Ca. Pelagibacter ubique.” Global differences in mRNA and protein expression between nitrogen-limited and nitrogen-replete cultures were measured to identify nitrogen stress responses in “Ca.Pelagibacter ubique” strain HTCC1062. Transporters for ammonium (AmtB), taurine (TauA), amino acids (YhdW), and opines (OccT) were all elevated in nitrogen-limited cells, indicating that they devote increased resources to the assimilation of nitrogenous organic compounds. Enzymes for assimilating amine into glutamine (GlnA), glutamate (GltBD), and glycine (AspC) were similarly upregulated. Differential regulation of the transcriptional regulator NtrX in the two-component signaling system NtrY/NtrX was also observed, implicating it in control of the nitrogen starvation response. Comparisons of the transcriptome and proteome supported previous observations of uncoupling between transcription and translation in nutrient-deprived “Ca.Pelagibacter ubique” cells. Overall, these data reveal a streamlined, PII-independent response to nitrogen stress in “Ca.Pelagibacter ubique,” and likely otherPelagibacterales, and show that they respond to nitrogen stress by allocating more resources to the assimilation of nitrogen-rich organic compounds.IMPORTANCEPelagibacteralesare extraordinarily abundant and play a pivotal role in marine geochemical cycles, as one of the major recyclers of labile dissolved organic matter. They are also models for understanding how streamlining selection can reshape chemoheterotroph metabolism. Streamlining and its broad importance to environmental microbiology are emerging slowly from studies that reveal the complete genomes of uncultured organisms. Here, we report another remarkable example of streamlined metabolism inPelagibacterales, this time in systems that control nitrogen assimilation.Pelagibacteralesare major contributors to metatranscriptomes and metaproteomes from ocean systems, where patterns of gene expression are used to gain insight into ocean conditions and geochemical cycles. The data presented here supply background that is essential to interpreting data from field studies.
Acupuncture Treatment of Chronic Low Back Pain Reverses An Abnormal Brain Default Mode Network in Correlation with Clinical Pain Relief
Authors: Li Ji , Zhang Jun-Hai , Yi Tao , Tang Wei-Jun , Wang Song-Wei , Dong Jing-Cheng 
Published: November 2013

Background Acupuncture is gaining in popularity as a treatment for chronic low back pain (cLBP); however, its therapeutic mechanisms remain controversial, partly because of the absence of an objective way of measuring subjective pain. Resting-state functional MRI (rsfMRI) has demonstrated aberrant default mode network (DMN) connectivity in patients with chronic pain, and also shown that acupuncture increases DMN connectivity in pain-modulator and affective-emotional brain regions of healthy subjects. Objective This study sought to explore how cLBP influences the DMN and whether, and how, the altered DMN connectivity is reversed after acupuncture for clinical pain. Methods RsfMRI data from 20 patients with cLBP, before and after 4 weeks of treatment, and 10 age- and gender-matched healthy controls (without treatment) were analysed using independent components analyses to determine connectivity within the DMN, and combined with correlation analyses to compute covariance between changes in DMN connectivity and changes in clinical pain. Visual analogue scale data were assessed to rate clinical pain levels. Results Less connectivity within the DMN was found in patients with cLBP than in healthy controls, mainly in the dorsolateral prefrontal cortex, medial prefrontal cortex, anterior cingulate gyrus and precuneus. After acupuncture, patients’ connectivities were restored almost to the levels seen in healthy controls. Furthermore, reductions in clinical pain were correlated with increases in DMN connectivity. Conclusions This result suggests that modulation of the DMN by acupuncture is related to its therapeutic effects on cLBP. Imaging of the DMN provides an objective method for assessment of the effects of acupuncture-induced analgesia.
ProANP plasma measurement predicts all-cause mortality in acutely hospitalised patients: a cohort study
Authors: Lauridsen Bo K , Iversen Kasper , Hunter Ingrid , Bay Morten , Kirk Vibeke , Nielsen Olav W , Nielsen Henrik , Boesgaard Søren , Køber Lars , Goetze Jens P 
Published: November 2013

ImportanceThe association of natriuretic peptide measurement with all-cause mortality in a broad selection of acutely admitted patients has not yet been examined.ObjectiveTo test the risk association between pro-atrial natriuretic peptide (ANP) and short-term and long-term mortality and its predictive value in acutely hospitalised patients and compare this to N-terminal B-type natriuretic peptide (NT-proBNP).Design, setting and patientsParticipants were selected from the Copenhagen Hospital Heart Failure Study (n=3644). Medical history, satisfactory echocardiography and blood samples were available on 2193 participants in 1998–1999 where NT-proBNP was measured. Vital status after discharge was obtained from national central data registers. A total of 1337 participants with eligible blood samples were selected in 2010–2011 for proANP measurement. Among these, 1255 (94%) were acutely hospitalised in 1998–1999.Main outcome measure(s)1-year and long-term mortality.ResultsMedian follow-up period was 11.5 years. At the end of follow-up, 926 patients had died, 239 during the first year. ProANP quartiles to 2–4 (median proANP levels 594 pmol/L, 990 pmol/L and 2052 pmol/L, respectively) associated with a stepwise increase in risk of 1-year and long-term mortality compared to the first quartile (336 pmol/L) in multivariable adjusted Cox proportional regression models (HR 1.53 95% CI 1.30 to 1.81 and HR 1.26 95% CI 1.17 to 1.36, respectively). An addition of NT-proBNP attenuated proANP's association with mortality in the models (HR 1.24 95% CI 1.01 to 1.53 and 1.14 95% CI 1.03 to 1.26, respectively). The increased risk was observed in participants with the highest proANP levels (fourth quartile). Similar results were observed in subgroups of participants with no evidence of cardiovascular disease (CVD). ProANP in quartiles improved discrimination when added to traditional risk factors in prediction models for 1-year (integrated discrimination improvement (IDI) 0.141 95% CI 0.085 to 0.197; C-index 0.753 95% CI 0.724 to 0.783, P for improvement 0.003) and long-term mortality (IDI 0.053 95% CI 0.032 to 0.074; C-index 0.736 95% CI 0.720 to 0.752, P for improvement <0.001) with similar results in subgroups. Discrimination was best in a combined model with proANP as well as NT-proBNP included.Conclusions and relevanceHigh plasma proANP concentrations are associated with and predict short-term and long-term all-cause mortality in acutely hospitalised patients irrespective of CVD status at admission.
Using ‘nudge’ principles for order set design: a before and after evaluation of an electronic prescribing template in critical care
Authors: Bourdeaux Christopher P , Davies Keith J , Thomas Matthew J C , Bewley Jeremy S , Gould Timothy H 
Published: November 2013

ObjectiveComputerised order sets have the potential to reduce clinical variation and improve patient safety but the effect is variable. We sought to evaluate the impact of changes to the design of an order set on the delivery of chlorhexidine mouthwash and hydroxyethyl starch (HES) to patients in the intensive care unit.MethodsThe study was conducted at University Hospitals Bristol NHS Foundation Trust, UK. Our intensive care unit uses a clinical information system (CIS). All drugs and fluids are prescribed with the CIS and drug and fluid charts are stored within a database. Chlorhexidine mouthwash was added as a default prescription to the prescribing template in January 2010. HES was removed from the prescribing template in April 2009. Both interventions were available to prescribe manually throughout the study period. We conducted a database review of all patients eligible for each intervention before and after changes to the configuration of choices within the prescribing system.Results2231 ventilated patients were identified as appropriate for treatment with chlorhexidine, 591 before the intervention and 1640 after. 55.3% were prescribed chlorhexidine before the change and 90.4% after (p<0.001). 6199 patients were considered in the HES intervention, 2177 before the intervention and 4022 after. The mean volume of HES infused per patient fell from 630 mL to 20 mL after the change (p<0.001) and the percentage of patients receiving HES fell from 54.1% to 3.1% (p<0.001). These results were well sustained with time.ConclusionsThe presentation of choices within an electronic prescribing system influenced the delivery of evidence-based interventions in a predictable way and the effect was well sustained. This approach has the potential to enhance the effectiveness of computerised order sets.
Chapter 4 Global distributional dynamics of Cambrian clades as revealed by Burgess Shale-type deposits
Authors: Hendricks Jonathan R. 
Published: November 2013

Abstract
The Cambrian geographical and temporal distributions of many clades remain poorly understood, despite their importance for elucidating the palaeobiogeographical context of the Cambrian radiation. New species and genus level occurrence databases were developed to analyse temporal and geographical distributional patterns in taxa belonging to 14 clades from over 60 globally distributed early and Middle Cambrian Burgess Shale-type lagerstätten. Analyses demonstrate that clades with confirmed Precambrian origins were, on average, more widespread and temporally persistent than clades with first fossil occurrences in the Cambrian. Despite their dominance in diversity, arthropods were less widely distributed and temporally persistent than many other groups. Finally, a significant correlation between geographical range and temporal persistence is demonstrated, supporting the hypothesis that Cambrian taxa with wider geographical ranges were less likely to go extinct than those with narrower ranges.

Supplementary material:

Species and genus data tables are available at:
http://www.geolsoc.org.uk/SUP18665
Deferred and atomic setting of scheduling attributes for ada
Authors: Sáez Sergio , Real Jorge , Crespo Alfons 
Published: November 2013

Deferred setting of scheduling attributes refers to a single operation that sets a new value for a scheduling attribute of a task at some future time. Although deferred setting of scheduling attributes is possible in Ada 2012, it is in a rather limited way: only deadline or CPU can be changed deferredly, either at a specified time or when the task is released from a suspension object. And only one of those two attributes at a time. Other scheduling attributes such as priority cannot have deferred setting by means of a single operation. This would be a convenient feature to have for schemes such as job partitioning, task splitting, or mode changes. Another issue is the absence of operations for atomically changing several parameters at a time, which would avoid scheduling issues specially on multiprocessor.
In this paper we explore a proposal aimed at correcting these two drawbacks. On one hand, we want to be able to change more attributes, not only deadlines, deferredly or immediately. On the other hand, we want to atomically change (now or later) a set of attributes, thereby avoiding scheduling artifacts that arise from sequentially changing several attributes, specially when the CPU is one of them. Rather than providing a number of library operations for postponing the setting of a variety of scheduling attributes, we propose to encapsulate the scheduling attributes of each task in a single tagged type that can be extended with more attributes for specific applications if needed.
Tumor Suppressor NF2/Merlin Is a Microtubule Stabilizer
Authors: Smole Zlatko , Thoma Claudio R. , Applegate Kathryn T. , Duda Maria , Gutbrodt Katrin L. , Danuser Gaudenz , Krek Wilhelm 
Published: November 2013

Abstract
Cancer-associated mutations in oncogene products and tumor suppressors contributing to tumor progression manifest themselves, at least in part, by deregulating microtubule-dependent cellular processes that play important roles in many cell biological pathways, including intracellular transport, cell architecture, and primary cilium and mitotic spindle organization. An essential characteristic of microtubules in the performance of these varied cell processes is their ability to continuously remodel, a phenomenon known as dynamic instability. It is therefore conceivable that part of the normal function of certain cancer-causing genes is to regulate microtubule dynamic instability. Here, we report the results of a high-resolution live-cell image-based RNA interference screen targeting a collection of 70 human tumor suppressor genes to uncover cancer genes affecting microtubule dynamic instability. Extraction and computational analysis of microtubule dynamics from EB3-GFP time-lapse image sequences identified the products of the tumor suppressor genes NF1 and NF2 as potent microtubule-stabilizing proteins. Further in-depth characterization of NF2 revealed that it binds to and stabilizes microtubules through attenuation of tubulin turnover by lowering both rates of microtubule polymerization and depolymerization as well as by reducing the frequency of microtubule catastrophes. The latter function appears to be mediated, in part, by inhibition of hydrolysis of tubulin-bound GTP on the growing microtubule plus end. Cancer Res; 74(1); 353–62. ©2013 AACR.
MUC1 in Macrophage: Contributions to Cigarette Smoke–Induced Lung Cancer
Authors: Xu Xiuling , Padilla Mabel T. , Li Bilan , Wells Alexandria , Kato Kosuke , Tellez Carmen , Belinsky Steven A. , Kim Kwang Chul , Lin Yong 
Published: November 2013

Abstract
Expression of the pro-oncogenic mucin MUC1 is elevated by inflammation in airway epithelial cells, but the contributions of MUC1 to the development of lung cancer are uncertain. In this study, we developed our finding that cigarette smoke increases Muc1 expression in mouse lung macrophages, where we hypothesized MUC1 may contribute to cigarette smoke–induced transformation of bronchial epithelial cells. In human macrophages, cigarette smoke extract (CSE) strongly induced MUC1 expression through a mechanism involving the nuclear receptor PPAR-γ. CSE-induced extracellular signal–regulated kinase (ERK) activation was also required for MUC1 expression, but it had little effect on MUC1 transcription. RNA interference–mediated attenuation of MUC1 suppressed CSE-induced secretion of TNF-α from macrophages, by suppressing the activity of the TNF-α–converting enzyme (TACE), arguing that MUC1 is required for CSE-induced and TACE-mediated TNF-α secretion. Similarly, MUC1 blockade after CSE induction through suppression of PPAR-γ or ERK inhibited TACE activity and TNF-α secretion. Conditioned media from CSE-treated macrophages induced MUC1 expression and potentiated CSE-induced transformation of human bronchial epithelial cells in a TNF-α–dependent manner. Together, our results identify a signaling pathway involving PPAR-γ, ERK, and MUC1 for TNF-α secretion induced by CSE from macrophages. Furthermore, our results show how MUC1 contributes to smoking-induced lung cancers that are driven by inflammatory signals from macrophages. Cancer Res; 74(2); 460–70. ©2013 AACR.
Defective TGF-β Signaling in Bone Marrow–Derived Cells Prevents Hedgehog-Induced Skin Tumors
Authors: Fan Qipeng , Gu Dongsheng , Liu Hailan , Yang Ling , Zhang Xiaoli , Yoder Mervin C. , Kaplan Mark H. , Xie Jingwu 
Published: November 2013

Abstract
Hedgehog signaling in cancer cells drives changes in the tumor microenvironment that are incompletely understood. Here, we report that hedgehog-driven tumors exhibit an increase in myeloid-derived suppressor cells (MDSC) and a decrease in T cells, indicative of an immunosuppressive tumor microenvironment. This change was associated with activated TGF-β signaling in several cell types in basal cell carcinomas. We determined that TGF-β signaling in bone marrow–derived cells, not keratinocytes, regulates MDSC and promotes tumor development. Tgfbr2 deficiency in the bone marrow–derived cells also reduced the size of previously developed tumors in mice. We identified CCL2 as the major chemokine attracting MDSCs to tumor, whose expression was Tgfbr2-dependent, whereas its receptor CCR2 was highly expressed in MDSC population. CCL2 alone was sufficient to induce migration of MDSCs. Moreover, the CCR2 inhibitors prevented MDSC migration toward skin cells in vitro, and reduced MDSC accumulation and hedgehog signaling–driven tumor development in mice. Our results reveal a signaling network critical for hedgehog signaling in cancer cells to establish an effective immunosuppressive microenvironment during tumor development. Cancer Res; 74(2); 471–83. ©2013 AACR.
The Echo Score Revisited
Authors: Nunes Maria Carmo P. , Tan Timothy C. , Elmariah Sammy , do Lago Rodrigo , Margey Ronan , Cruz-Gonzalez Ignacio , Zheng Hui , Handschumacher Mark D. , Inglessis Ignacio , Palacios Igor F. , Weyman Arthur E. , Hung Judy 
Published: November 2013

Background—
Current echocardiographic scoring systems for percutaneous mitral valvuloplasty (PMV) have limitations. This study examined new, more quantitative methods for assessing valvular involvement and the combination of parameters that best predicts immediate and long-term outcome after PMV.

Methods and Results—

Two cohorts (derivation n=204 and validation n=121) of patients with symptomatic mitral stenosis undergoing PMV were studied. Mitral valve morphology was assessed by using both the conventional Wilkins qualitative parameters and novel quantitative parameters, including the ratio between the commissural areas and the maximal excursion of the leaflets from the annulus in diastole. Independent predictors of outcome were assigned a points value proportional to their regression coefficients: mitral valve area ≤1 cm
2
(2), maximum leaflets displacement ≤12 mm (3), commissural area ratio ≥1.25 (3), and subvalvular involvement (3). Three risk groups were defined: low (score of 0–3), intermediate (score of 5), and high (score of 6–11) with observed suboptimal PMV results of 16.9%, 56.3%, and 73.8%, respectively. The use of the same scoring system in the validation cohort yielded suboptimal PMV results of 11.8%, 72.7%, and 87.5% in the low-, intermediate-, and high-risk groups, respectively. The model improved risk classification in comparison with the Wilkins score (net reclassification improvement 45.2%;
P
<0.0001). Long-term outcome was predicted by age and postprocedural variables, including mitral regurgitation, mean gradient, and pulmonary pressure.

Conclusions—
A scoring system incorporating new quantitative echocardiographic parameters more accurately predicts outcome following PMV than existing models. Long-term post-PMV event-free survival was predicted by age, degree of mitral regurgitation, and postprocedural hemodynamic data.
A Novel Multiscale Intensity Metric for Evaluation of Tropical Cyclone Intensity Forecasts
Authors: Vukicevic Tomislava , Uhlhorn Eric , Reasor Paul , Klotz Bradley 
Published: November 2013

Abstract
In this study, a new multiscale intensity (MSI) metric for evaluating tropical cyclone (TC) intensity forecasts is presented. The metric consists of the resolvable and observable, low-wavenumber intensity represented by the sum of amplitudes of azimuthal wavenumbers 0 and 1 for wind speed within the TC vortex at the radius of maximum wind and a stochastic residual, all determined at 10-m elevation. The residual wind speed is defined as the difference between an estimate of maximum speed and the low-wavenumber intensity. The MSI metric is compared to the standard metric that includes only the maximum speed. Using stepped-frequency microwave radiometer wind speed observations from TC aircraft reconnaissance to estimate the low-wavenumber intensity and the National Hurricane Center’s best-track (BT) intensity for the maximum wind speed estimate, it is shown that the residual intensity is well represented as a stochastic quantity with small mean, standard deviation, and absolute norm values that are within the expected uncertainty of the BT estimates. The result strongly suggests that the practical predictability of TC intensity is determined by the observable and resolvable low-wavenumber intensity within the vortex. Verification of a set of high-resolution numerical forecasts using the MSI metric demonstrates that this metric provides more informative and more realistic estimates of the intensity forecast errors. It is also shown that the maximum speed metric allows for error compensation between the low-wavenumber and residual intensities, which could lead to forecast skill overestimation and inaccurate assessment of the impact of forecast system change on the skill.
Subcloud-Layer Feedbacks Driven by the Mass Flux of Shallow Cumulus Convection over Land
Authors: van Stratum Bart J. H. , Vilá-Guerau de Arellano Jordi , van Heerwaarden Chiel C. , Ouwersloot Huug G. 
Published: November 2013

AbstractThe processes and feedbacks associated with the mass flux of shallow cumulus clouds over land are studied by analyzing the results from large-eddy simulations and a mixed-layer model. The primary focus is to study the development of the (well mixed) subcloud layer and understand the four primary feedbacks between the subcloud-layer dynamics and cumulus mass flux. Guided by numerical experiments in large-eddy simulations that show the transition from clear to cloudy boundary layers at midlatitudes over land, the feedbacks introduced by shallow cumuli are first conceptually described. To study the complex interplay between the subcloud and cloud layer, a mixed-layer model is proposed and validated with large-eddy simulations for the Atmospheric Radiation Measurement Southern Great Plains case. The mixed-layer model is shown to identify and reproduce the most relevant feedbacks in the transition from clear to cloudy boundary layers: a reduced mixed-layer growth and drying of the subcloud layer by enhanced entrainment and mass flux transport of moisture to the cloud layer. To complete the study, the strength of the different feedbacks is further quantified by an analysis of the individual contributions to the tendency of the relative humidity at the top of the mixed layer.