bluuebunny/crossref_metadata_2025 huggingface dataset:
Fecal markers of inflammation, protein loss, and microbial changes in dogs with the acute hemorrhagic diarrhea syndrome (AHDS)
Authors: Heilmann Romy M. , Guard Melissa M. , Steiner Jörg M. , Suchodolski Jan S. , Unterer Stefan
Published: August 2017

Background

Idiopathic acute hemorrhagic diarrhea syndrome (AHDS) is characterized by acute onset of bloody diarrhea, severe dehydration, and increased vascular and intestinal mucosal permeability. Markers of gastrointestinal inflammation, protein loss, and changes in the intestinal microbiota have not been studied extensively in dogs with AHDS.

Key Findings

For 3 consecutive days, feces were collected from dogs with AHDS, and assayed for calprotectin and S100A12 (both markers of inflammation), α1‐proteinase inhibitor (a marker of gastrointestinal protein loss), and the presence of selected species of bacteria. Concentrations of all assayed markers were significantly greater than the institutional reference intervals at the time of presentation, and all decreased significantly by Day 3 of treatment. Abundances of selected bacterial groups (Ruminococcaceae, Faecalibacterium spp., Bifidobacterium spp., and Proteobacteria) at the time of diagnosis were consistent with an intestinal bacterial dysbiosis. No differences in the abundance of bacterial groups over time was seen, except for a mild but significant decrease in Ruminococcaceae at Day 3.

Significance

These results suggest that canine AHDS is associated with a significant but transient gastrointestinal loss of protein and intestinal inflammation. The intestinal bacterial dysbiosis appears to outlast the protein loss and inflammation.
Surgical management and long‐term outcome of umbilical infection in 65 foals (2010‐2015)
Authors: Oreff Gil L. , Tatz Amos J. , Dahan Roee , Segev Gilad , Berlin Dalia , Kelmer Gal
Published: August 2017

Objective

To report the short‐ and long‐term outcomes of surgical management of umbilical infection in foals.

Study design

Retrospective case series.

Animals

Foals (n = 65).

Methods

Medical records (2010‐2015) of foals up to 1 month of age, surgically treated for an umbilical infection were reviewed. Short‐term (at the time of discharge from hospital) and long‐term (1 year after surgery) survival rates were obtained. Clinical variables influencing survival were assessed. Chi‐square or Fisher's exact test were used to evaluate the relationship between the data retrieved and outcome.P ≤ .05 was considered statistically significant.

Results

Sixty‐five foals were included in the study, representing 17.2% of all foals admitted to the hospital. Fifty foals were discharged from hospital (77%) and 43 foals (66%) were alive 1 year after surgery. Lower long‐term survival rates were associated with: younger age at presentation, septic joints, multiple pathologies, higher creatinine level, higher heart rate, umbilical infection diagnosed at the hospital rather than prior to referral, prolonged hospitalization, longer period between arrival and surgery, and postoperative complications. The most common surgical findings were urachal enlargement followed by right arterial enlargement.

Conclusion

Younger foals with worse systemic condition and concurrent disorders are at higher risk for treatment failure. Early diagnosis improves the outcome. Surgical treatment yields good results and should be considered upon diagnosis, after taking into account the clinical situation.

Clinical significance

Based on the results of this study, diagnosis and surgical management of umbilical infection in neonatal foals should be performed as early as possible, and a good outcome can be expected after surgery.
Effect of arthroscopic lavage and repeated intra‐articular administrations of antibiotic in adult horses and foals with septic arthritis
Authors: Cousty Matthieu , David Stack John , Tricaud Cyril , David Florent
Published: August 2017

Objective

To evaluate the effect of arthroscopic lavage and repeated intra‐articular administration of antibiotic in adult horses and foals with septic arthritis.

Study design

Retrospective clinical study.

Animals

Adult horses and foals with septic arthritis (n = 62).

Methods

Age, sex, cause of septic synovitis, joint involved, hospitalization time, and outcome were recorded. Arthroscopic lavage was performed at day 0 (D 0). Synovial fluid was collected every 48 hours prior to intra‐articular administration of antibiotic, and until hospital discharge. Synovial nucleated cell count, total protein, and percentage of neutrophils were compared across time and between subjects with a favorable or unfavorable outcome.

Results

Synovial nucleated cell counts decreased progressively and were lower at all times compared to D 0. Percentages of neutrophils were lower than baseline at D 8 and 10, only. Total protein contents decreased progressively and were lower than baseline at D 2, 4, 6, 8, 10, and 14. When adult horses and foals with a favorable outcome were compared to those with an unfavorable outcome, the nucleated cell count was lower at D 10, 12, and 14 and the percentage of neutrophils was lower at D 4 only, but total protein content did not differ between groups at any time.

Conclusion

Synovial nucleated cell counts and total protein concentrations decreased after arthroscopic lavage and repeated intra‐articular administration of antibiotic in horses and foals with septic arthritis. Synovial nucleated cell count is limited as a monitoring tool during treatment of septic arthritis.
Human regulatory macrophages are potent in suppression of the xenoimmune response via indoleamine‐2,3‐dioxygenase‐involved mechanism(s)
Authors: Guo Fei , Hu Min , Huang Dandan , Zhao Yuanfei , Heng Benjamin , Guillemin Gilles , Lim Chai K. , Hawthorne Wayne J. , Yi Shounan
Published: August 2017

Background

For xenotransplantation to truly succeed, we must develop immunomodulatory strategies to suppress the xenoimmune response but by minimizing immunosuppression over the long term. Regulatory macrophages (Mreg) have been shown to suppress polyclonal T‐cell proliferation in vitro and prolong allograft survival in vivo. However, the question of whether they are capable of suppressing xenoimmune responses remains unknown. This study assessed the potential of human Mreg to be used as an effective immunomodulatory method in xenotransplantation.

Methods

CD14+ monocytes selected from human peripheral blood mononuclear cells (PBMC) were cultured with macrophage colony‐stimulating factor (M‐CSF) for 7 days with IFN‐γ added at day 6 for Mreg induction. Mreg phenotyping was performed by flow cytometric analysis, and the in vitro suppressive function was assessed by mixed lymphocyte reaction (MLR) using irradiated pig PBMC as the xenogeneic stimulator cells, human PBMC as responder cells, and autologous Mreg as suppressor cells. To assess mRNA expression of Mreg functional molecules indoleamine‐2,3‐dioxygenase (IDO), IL‐10, inducible nitric oxide synthase (iNOS) and TGF‐β were measured by real‐time PCR. Supernatants were collected from the MLR cultures for IDO activity assay by high‐performance liquid chromatography (HPLC). The effects of the IDO inhibitor 1‐D/L‐methyl‐tryptophan (1‐MT), iNOS inhibitor NG‐monomethyl‐l‐arginine (L‐NMMA), and anti‐IFN‐γ or anti‐TGF‐β monoclonal antibody (mAb) treatment on Mreg suppressive capacity were tested from the supernatants of the MLR assays.

Results

We demonstrated that induced Mreg with a phenotype of CD14lowCD16−/lowCD80lowCD83−/lowCD86+/hiHLA‐DR+/hi were capable of suppressing proliferating human PBMC, CD4+, and CD8+ T cells, even at a higher responder:Mreg ratio of 32:1 in a pig‐human xenogeneic MLR. The strong suppressive potency of Mreg was further correlated with their upregulated IDO expression and activity. The IDO upregulation of Mreg was associated with an increased production of IFN‐γ, an IDO stimulator, by xenoreactive responder cells in the xenogeneic MLR. While no effect on Mreg suppressive potency was detected by addition of the iNOS inhibitor L‐NMMA or anti‐TGF‐β mAb into the MLR assays, inhibition of IDO activity by neutralizing IFN‐γ or by IDO inhibitor 1‐MT substantially impaired the capacity of Mreg to suppress the xenogeneic response, indicating the importance of upregulated IDO activity in Mreg‐mediated suppression of the xenogeneic response in vitro.

Conclusion

This study demonstrates that human Mreg are capable of suppressing the xenoimmune response in vitro via IDO‐involved mechanism(s), suggesting their potential role as an effective immunomodulatory tool in xenotransplantation.
A Needs Assessment for the Adoption of Next Generation Science Standards (NGSS) in K-12 Education in the United States
Authors: Harris Karleah , Sithole Alec , Kibirige Joachim
Published: August 2017

Since its inception, the Next Generation Science Standards (NGSS) blue print has attracted interest from more than 40 states in the United States. The overall objective of these proposed changes is to align K-12 science education with current trends in technology and career needs. However, the assessment of teacher preparedness and classroom technology needs is still a critical factor in the implementation of these changes. Our study conducted a needs and preparedness assessment using online surveys on public K-12 teachers before the implementation phase. The data collected for this study comprised 214 responses from schools in 16 states across the US. The study indicates that most of the teachers were not knowledgably equipped to fuse the proposed changes in standards with the current curricula and their teaching plans. The teachers made several suggestions, based on their views regarding the level of preparedness of their students. The implications of these findings and suggestions for further adjustments are presented and discussed.
Comparison between China and the United States in Solar Energy Development
Authors: Fuller Jack , Guo Yang
Published: August 2017

The popularity and importance of solar power generation in the United States and China continues to increase. This research effort investigated the present status of solar power generation in both countries. The solar installation incentives provided by the two governments were analyzed. Comparisons between the countries would also focus on: (1) solar electricity generation capacity, (2) solar energy policy comparisons, (3) economic effects of solar energy development, and (4) future solar energy challenges. Conclusions would then be discussed on the comparison topics.
Experimental and modelling evidence of shortening heat in cardiac muscle
Authors: Tran Kenneth , Han June‐Chiew , Crampin Edmund John , Taberner Andrew James , Loiselle Denis Scott
Published: August 2017

Key points

Heat associated with muscle shortening has been repeatedly demonstrated in skeletal muscle, but its existence in cardiac muscle remains contentious after five decades of study.

By iterating between experiments and computational modelling, we show compelling evidence for the existence of shortening heat in cardiac muscle and reveal, mechanistically, the source of this excess heat.

Our results clarify a long‐standing uncertainty in the field of cardiac muscle energetics.

We provide a revised partitioning of cardiac muscle energy expenditure to include this newly revealed thermal component.

When a muscle shortens against an afterload, the heat that it liberates is greater than that produced by the same muscle contracting isometrically at the same level of force. This excess heat is defined as ‘shortening heat’, and has been repeatedly demonstrated in skeletal muscle but not in cardiac muscle. Given the micro‐structural similarities between these two muscle types, and since we imagine that shortening heat is the thermal accompaniment of cross‐bridge cycling, we have re‐examined this issue. Using our flow‐through microcalorimeter, we measured force and heat generated by isolated rat trabeculae undergoing isometric contractions at different muscle lengths and work‐loop (shortening) contractions at different afterloads. We simulated these experimental protocols using a thermodynamically constrained model of cross‐bridge cycling and probed the mechanisms underpinning shortening heat. Predictions generated by the model were subsequently validated by a further set of experiments. Both our experimental and modelling results show convincing evidence for the existence of shortening heat in cardiac muscle. Its magnitude is inversely related to the afterload or, equivalently, directly related to the extent of shortening. Computational simulations reveal that the heat of shortening arises from the cycling of cross‐bridges, and that the rate of ATP hydrolysis is more sensitive to change of muscle length than to change of afterload. Our results clarify a long‐standing uncertainty in the field of cardiac muscle energetics.
Wave-Induced Accelerations of a Fish-Farm Elastic Floater: Experimental and Numerical Studies
Authors: Li Peng , Faltinsen Odd M. , Greco Marilena
Published: August 2017

Numerical simulations and experiments of an elastic circular collar of a floating fish farm are reported. The floater model without netting structure is moored with nearly horizontal moorings and tested in regular deep-water waves of different steepnesses and periods without current. Local overtopping of waves was observed in steep waves. The focus here is on the vertical accelerations along the floater in the different conditions. The experiments show that higher-order harmonics of the accelerations matter. A three-dimensional (3D) weak-scatter model with partly nonlinear effects as well as a 3D linear frequency-domain method based on potential flow are used. From their comparison against the measurements, strong 3D and frequency dependency effects as well as flexible floater motions matter. The weak-scatter model can only partly explain the nonlinearities present in the measured accelerations.
Large Eddy Simulation and CDNS Investigation of T106C Low-Pressure Turbine
Authors: Hu Site , Zhou Chao , Xia Zhenhua , Chen Shiyi
Published: August 2017

This study investigates the aerodynamic performance of a low-pressure turbine, namely the T106C, by large eddy simulation (LES) and coarse grid direct numerical simulation (CDNS) at a Reynolds number of 100,000. Existing experimental data were used to validate the computational fluid dynamics (CFD) tool. The effects of subgrid scale (SGS) models, mesh densities, computational domains and boundary conditions on the CFD predictions are studied. On the blade suction surface, a separation zone starts at a location of about 55% along the suction surface. The prediction of flow separation on the turbine blade is always found to be difficult and is one of the focuses of this work. The ability of Smagorinsky and wall-adapting local eddy viscosity (WALE) model in predicting the flow separation is compared. WALE model produces better predictions than the Smagorinsky model. CDNS produces very similar predictions to WALE model. With a finer mesh, the difference due to SGS models becomes smaller. The size of the computational domain is also important. At blade midspan, three-dimensional (3D) features of the separated flow have an effect on the downstream flows, especially for the area near the reattachment. By further considering the effects of endwall secondary flows, a better prediction of the flow separation near the blade midspan can be achieved. The effect of the endwall secondary flow on the blade suction surface separation at the midspan is explained with the analytical method based on the Biot–Savart Law.
Validated Simulations of Heat Transfer From a Vertical Heated-Rod Array to a Helium-Filled Isothermal Enclosure
Authors: Maharjan Dilesh , Hadj-Nacer Mustafa , Chalasani Narayana , Greiner Miles
Published: August 2017

Measurements of heat transfer from an array of vertical heater rods to the walls of a square, helium-filled enclosure are performed for a range of enclosure temperatures, helium pressures, and rod heat generation rates. This configuration is relevant to a used nuclear fuel assembly within a dry storage canister. The measurements are used to assess the accuracy of computational fluid dynamics (CFD)/radiation simulations in the same configuration. The simulations employ the measured enclosure temperatures as boundary conditions and predict the temperature difference between the rods and enclosure. These temperature differences are as large as 72 °C for some experiments. The measured temperature of rods near the periphery of the array is sensitive to small, uncontrolled variations in their location. As a result, those temperatures are not as useful for validating the simulations as measurements from rods near the array center. The simulated rod temperatures exhibit random differences from the measurements that are as large as 5.7 °C, but the systematic (average) error is 1 °C or less. The random difference between the simulated and measured maximum array temperature is 2.1 °C, which is less than 3% of the maximum rod-to-wall temperature difference.
Lateral Edge Effects on the Sherwood Number in Turbulent Flow Over a Flat Plate
Authors: Taliaferro Matthew E. , Fassio Federico , Gori Fabio , Simon Terrence W. , Goldstein Richard J.
Published: August 2017

Experimental results for the Sherwood number variation near the lateral edge of the active surface of a smooth, finite-width flat plate in turbulent boundary layer flow are presented. Using naphthalene sublimation, local mass transfer rates are found for two different free stream velocities. A semi-empirical correlation of the experimental data is presented, allowing calculation of the increase of mass transfer near the edge and the size of the region affected by the lateral edge. The effect is shown to scale more so with the diffusion thickness than the boundary layer thickness.
Investigation of the sound generation mechanisms for in-duct orifice plates
Authors: Tao Fuyang , Joseph Phillip , Zhang Xin , Stalnov Oksana , Siercke Matthias , Scheel Henning
Published: August 2017

Sound generation due to an orifice plate in a hard-walled flow duct which is commonly used in air distribution systems (ADS) and flow meters is investigated. The aim is to provide an understanding of this noise generation mechanism based on measurements of the source pressure distribution over the orifice plate. A simple model based on Curle's acoustic analogy is described that relates the broadband in-duct sound field to the surface pressure cross spectrum on both sides of the orifice plate. This work describes careful measurements of the surface pressure cross spectrum over the orifice plate from which the surface pressure distribution and correlation length is deduced. This information is then used to predict the radiated in-duct sound field. Agreement within 3 dB between the predicted and directly measured sound fields is obtained, providing direct confirmation that the surface pressure fluctuations acting over the orifice plates are the main noise sources. Based on the developed model, the contributions to the sound field from different radial locations of the orifice plate are calculated. The surface pressure is shown to follow a U3.9 velocity scaling law and the area over which the surface sources are correlated follows a U1.8 velocity scaling law.
A Laplace transform method for molecular mass distribution calculation from rheometric data
Authors: Lang C.
Published: August 2017

Polydisperse linear polymer melts can be microscopically described by the tube model and fractal reptation dynamics, while on the macroscopic side the generalized Maxwell model is capable of correctly displaying most of the rheological behavior. In this paper, a Laplace transform method is derived and different macroscopic starting points for molecular mass distribution calculation are compared to a classical light scattering evaluation. The underlying assumptions comprise the modern understanding on polymer dynamics in entangled systems but can be stated in a mathematically generalized way. The resulting method is very easy to use due to its mathematical structure, and it is capable of calculating multimodal molecular mass distributions of linear polymer melts.
Are Measures Derived From Land Use and Transport Policies Associated With Walking for Transport?
Authors: Rachele Jerome N. , Learnihan Vincent , Badland Hannah M. , Mavoa Suzanne , Turrell Gavin , Giles-Corti Billie
Published: August 2017

Background: There is growing urgency for higher quality evidence to inform policy. This study developed geographic information system spatial measures based on land use and transport policies currently used in selected Australian states to assess which, if any, of these measures were associated with walking for transport. Methods: Overall, 6901 participants from 570 neighborhoods in Brisbane, Australia, were included. Participants reported their minutes of walking for transport in the previous week. After a review of state-level land use and transport policies relevant to walking for transport across Australia, 7 geographic information system measures were developed and tested based on 9 relevant policies. Data were analyzed using multilevel multinomial logistic regression. Results: Greater levels of walking for transport were associated with more highly connected street networks, the presence of public transport stops, and having at least 2 public transport services per hour. Conversely, neighborhoods with shorter cul-de-sac lengths had lower levels of walking for transport. There was no evidence of associations between walking for transport and street block lengths less than 240 m or traffic volumes. Conclusions: These findings highlight the need for urban design and transport policies developed by governments to be assessed for their impact on transport-related physical activity.
Effect of Exercise on Inflammatory Profile of Older Persons: Systematic Review and Meta-Analyses
Authors: Monteiro-Junior Renato Sobral , de Tarso Maciel-Pinheiro Paulo , da Matta Mello Portugal Eduardo , da Silva Figueiredo Luiz Felipe , Terra Rodrigo , Carneiro Lara S. F. , Rodrigues Vinícius Dias , Nascimento Osvaldo J. M. , Deslandes Andrea Camaz , Laks Jerson
Published: August 2017

Background: Inflammatory cytokines and acute phase proteins increase with aging, promoting a chronic low-grade inflammation. Studies have shown a positive effect of exercise on inflammatory markers in older persons. Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) are the main biomarkers investigated. However, it is unclear if exercise could decrease all these biomarkers. Purpose: The aim was to analyze the effect of chronic exercise on IL-6, TNF-α, and CRP levels in older persons. Methods: Preferred Reporting Items in Systematic Reviews and Meta-analyses guidelines were adopted. Original articles that investigated the effect of chronic exercise on inflammatory profile of the elderly persons were eligible for this review. The databases PubMed, PEDro, EBSCO, and BioMed Central were searched. Three reviewers evaluated each publication for reducing bias. Data about IL-6, TNF-α, and CRP were collected and analyzed. A standardized mean difference based on estimated pooled effect size was calculated considering heterogeneity index (I2) and random effect. Results: Seventy-six studies were retrieved from databases, and 8 of them were analyzed. IL-6 and CRP levels decreased after chronic exercise (overall effect P < .05). Conclusion: Regular exercise decreases IL-6 and CRP levels in older persons. The effect of exercise on TNF-α remains unclear.
Teacher Development in First-Year Physical Educators: A Comparison of Effectiveness Among Different Physical Education Teacher Education Backgrounds
Authors: Ensign Julene , Woods Amelia Mays , Kulinna Pamela Hodges
Published: August 2017

Purpose:

This study evaluated the teaching effectiveness of six first-year physical educators, three Southwestern and three Midwestern graduates, employing different curricular approaches.

Method:

Utilizing surveys, interviews, questionnaires, and systematic observations, data were analyzed through a framework of seven essential teaching tasks (Rink, 2002).

Results:

Data indicated overall mean scores of 34% motor appropriate activity with Academic Learning Time-Physical Education (ALT-PE) and a rating of 70.37 on the Qualitative Measures of Teacher Performance Scale (QMTPS). Notable contrasts included higher mean scores for Southwest participants for motor-appropriate and motor-inappropriate activity. Midwest participants devoted more time to game situations, management, and social behavior. For QMTPS, Southwest means were higher in every category. Qualitative themes produced similarities in teaching philosophy, fidelity to preservice training, and perceived value of reflective practices. Contrasts existed in curricular emphases and approaches to classroom management.

Discussion/Conclusion:

Characteristics of effective teaching were demonstrated by all participants regardless of curricular emphasis.
Exploring the Nature of Counterfactual Thinking and Their Perceived Consequences in an Elite Sporting Context: An Interpretative Phenomenological Analysis
Authors: Marlow Jack A. G. , Uphill Mark
Published: August 2017

This study explored the characteristics, contextual factors and consequences of counterfactual thoughts in seven elite athletes using interpretative phenomenological analysis (IPA). Counterfactuals were experienced regularly with self-directed and upward counterfactuals (cognitions about how things could be better) being most frequent. These upward counterfactuals typically occurred following performance that was below participants’ goals and expectations. These thoughts were perceived by participants to have a negative affect initially, and that they then led to facilitative behavioral consequences around learning and development. Some elements of counterfactual thinking could be used as a useful reflective tool to encourage elite athletes to problem solve and motivate cognitive, emotional and behavioral change to enhance future performance.
Stress drops of induced and tectonic earthquakes in the central United States are indistinguishable
Authors: Huang Yihe , Ellsworth William L. , Beroza Gregory C.
Published: August 2017

Induced earthquakes have comparable stress drop and ground motion to natural earthquakes given similar depths and faulting styles.
Polycomb repressive complex 1 modifies transcription of active genes
Authors: Pherson Michelle , Misulovin Ziva , Gause Maria , Mihindukulasuriya Kathie , Swain Amanda , Dorsett Dale
Published: August 2017

The PRC1 complex keeps genes silent during development, and these studies show that it also controls genes that are active.
Anthrax cousin wreaks havoc in the rainforest
Authors: Kupferschmidt Kai
Published: August 2017

Bacillus cereus
, a microbe widely seen as benign, is a mass killer of mammals, researchers say.
Elderly chimps may get Alzheimer's disease
Authors: Cross Ryan
Published: August 2017

Hallmark plaques and tangles found in the largest analysis yet of old chimp brains.
House of the sun
Authors: Loomis Ilima
Published: August 2017

How astronomers built the world's largest solar telescope on Maui even as protesters derailed a larger telescope one island away.
The microbial metabolite desaminotyrosine protects from influenza through type I interferon
Authors: Steed Ashley L. , Christophi George P. , Kaiko Gerard E. , Sun Lulu , Goodwin Victoria M. , Jain Umang , Esaulova Ekaterina , Artyomov Maxim N. , Morales David J. , Holtzman Michael J. , Boon Adrianus C. M. , Lenschow Deborah J. , Stappenbeck Thaddeus S.
Published: August 2017

Eat more plants for influenza resilience

Antibiotic treatment worsens influenza in mice, possibly because the concomitant loss of the microbiota interrupts the production of bioactive metabolites. Steed
et al.
found that a microbial product, desaminotyrosine (DAT), produced by an obligate clostridial anaerobe from the digestion of plant flavonoids, is beneficial during influenza. DAT enters the bloodstream and triggers type I interferon signaling, which then augments antiviral responses by phagocytic cells. Without DAT, influenza virus causes inflammation and severe disease.

Science
, this issue p.
498
Complete measurement of helicity and its dynamics in vortex tubes
Authors: Scheeler Martin W. , van Rees Wim M. , Kedia Hridesh , Kleckner Dustin , Irvine William T. M.
Published: August 2017

Linking fluids as they twist and writhe

Helicity is a measure of cork-screw-like motion described by the amount of twisting, writhing, and linking in a fluid. Total helicity is conserved for ideal fluids, but how helicity changes in real fluids with even tiny amounts of viscosity has been an open question. Scheeler
et al.
provide a complete measurement of total helicity in a real fluid by using a set of hydrofoils to track linking, twisting, and writhing (see the Perspective by Moffatt). They show that twisting dissipates total helicity, whereas writhing and linking conserve it. This provides a fundamental insight into tornadogenesis, atmospheric flows, and the formation of turbulence.

Science
, this issue p.
487
; see also p.
448
Estimating the health benefits of environmental regulations
Authors: McGartland Al , Revesz Richard , Axelrad Daniel A. , Dockins Chris , Sutton Patrice , Woodruff Tracey J.
Published: August 2017

Changes needed for complete benefits assessment
Genomic estimation of complex traits reveals ancient maize adaptation to temperate North America
Authors: Swarts Kelly , Gutaker Rafal M. , Benz Bruce , Blake Michael , Bukowski Robert , Holland James , Kruse-Peeples Melissa , Lepak Nicholas , Prim Lynda , Romay M. Cinta , Ross-Ibarra Jeffrey , Sanchez-Gonzalez Jose de Jesus , Schmidt Chris , Schuenemann Verena J. , Krause Johannes , Matson R. G. , Weigel Detlef , Buckler Edward S. , Burbano Hernán A.
Published: August 2017

Estimating temperate adaptation in ancient maize

Maize as a staple food crop in temperate North America required adaptation to a shorter growing season. On its first introduction in the southwestern United States ∼4000 years ago, maize was extensively grown in the lowlands. Cultivation in the temperate uplands did not occur for another 2000 years. Swarts
et al.
used ancient DNA data from 1900-year-old maize cobs found in a temperate cave in the southwestern United States and mapped the ancient flowering phenotype. The ancient maize samples were marginally adapted to temperate regions as a result of selection on standing variation.

Science
, this issue p.
512
UBE2O is a quality control factor for orphans of multiprotein complexes
Authors: Yanagitani Kota , Juszkiewicz Szymon , Hegde Ramanujan S.
Published: August 2017

Removing orphan proteins from the system

The degradation of excess subunits of protein complexes is a major quality-control problem for the cell. How such “orphans” are recognized and tagged for degradation is poorly understood. Two papers identify a protein quality-control pathway that acts on some of the most abundant protein complexes in the human body: hemoglobin and ribosomes (see the Perspective by Hampton and Dargemont). Yanagitani
et al.
show that the central player in this process is an unusual enzyme (UBE2O) that recognizes substrates and tags them for destruction. Other quality-contr ol pathways tend to use separate factors for target selection (often a chaperone), ubiquitin donation (an E2), and ubiquitin conjugati on (an E3). Encoding all three activities in a single factor whose function can be reconstituted in a purified system provides a tractable route to detailed mechanistic and structural dissection. Nguyen
et al.
show the importance of the UBE2O pathway in the differentiation of red blood cells.

Science
, this issue p.
472
, p.
471
; see also p.
450
UBE2O remodels the proteome during terminal erythroid differentiation
Authors: Nguyen Anthony T. , Prado Miguel A. , Schmidt Paul J. , Sendamarai Anoop K. , Wilson-Grady Joshua T. , Min Mingwei , Campagna Dean R. , Tian Geng , Shi Yuan , Dederer Verena , Kawan Mona , Kuehnle Nathalie , Paulo Joao A. , Yao Yu , Weiss Mitchell J. , Justice Monica J. , Gygi Steven P. , Fleming Mark D. , Finley Daniel
Published: August 2017

Removing orphan proteins from the system

The degradation of excess subunits of protein complexes is a major quality-control problem for the cell. How such “orphans” are recognized and tagged for degradation is poorly understood. Two papers identify a protein quality-control pathway that acts on some of the most abundant protein complexes in the human body: hemoglobin and ribosomes (see the Perspective by Hampton and Dargemont). Yanagitani
et al.
show that the central player in this process is an unusual enzyme (UBE2O) that recognizes substrates and tags them for destruction. Other quality-contr ol pathways tend to use separate factors for target selection (often a chaperone), ubiquitin donation (an E2), and ubiquitin conjugati on (an E3). Encoding all three activities in a single factor whose function can be reconstituted in a purified system provides a tractable route to detailed mechanistic and structural dissection. Nguyen
et al.
show the importance of the UBE2O pathway in the differentiation of red blood cells.

Science
, this issue p.
472
, p.
eaan0218
; see also p.
450
New developments for protein quality control
Authors: Hampton Randolph Y. , Dargemont Catherine
Published: August 2017

A unique enzyme promotes degradation of misfolded proteins and differentiation of red blood cells
Scientists can't be silent
Authors: Coons Christopher
Published: August 2017

In an era of rapid technological change and an increasingly global economy, investments in research and development are crucial for spurring economic growth and sustaining competitiveness. Yet, across the U.S. federal government, scientists are playing a decreasing role in the policymaking that supports this investment, often being pushed out by a political agenda that is stridently antiscience. Meanwhile, Americans are becoming more distrustful of democratic institutions, the scientific method, and basic facts—three core beliefs on which the research enterprise depends. The United States remains the unquestioned global leader in science and innovation, but given a White House that disregards the value of science and an American public that questions the very concept of scientific consensus, sustaining the U.S. commitment to science won't happen without a fight.
Improved Serodiagnostic Performance for Lyme Disease by Use of Two Recombinant Proteins in Enzyme-Linked Immunosorbent Assay Compared to Standardized Two-Tier Testing
Authors: Bradshaw Gary L. , Thueson R. Kelley , Uriona Todd J.
Published: August 2017

The most reliable test method for the serological confirmation of Lyme disease (LD) is a 2-tier method recommended by the CDC in 1995. The first-tier test is a low-specificity enzyme-linked immunosorbent assay (ELISA), and the second-tier tests are higher-specificity IgG and IgM Western blots. This study describes the selection of two
Borrelia burgdorferi
recombinant proteins and evaluation of their performance in a simple 1-tier test for the serological confirmation of LD. These two proteins were generated from (i) the full-length
dbpA
gene combined with the invariable region 6 of the
vlsE
gene (DbpA/C6) and (b) the full-length
ospC
gene (OspC). The expressed DbpA/C6 and OspC proteins were useful in detecting anti-
Borrelia
IgG and IgM antibodies, respectively. A blind study was conducted on a well-characterized panel of 279 human sera from the CDC, comparing ELISAs using these two recombinant antigens with the 2-tier test method. The two methods (DbpA/C6-OspC versus 2-tier test) were equivalent in identifying sera from negative-control subjects (99% and 100% specificity, respectively) and in detecting stage II and III LD patient sera (100% and 100% sensitivity). However, the DbpA/C6-OspC ELISA was markedly better (80% versus 63%) than the 2-tier test method in detecting anti-
Borrelia
antibodies in stage I LD patients. The findings suggest that these antigens could be used in a simple 1-tier ELISA that is faster to perform, easier to interpret, and less expensive than the 2-tier test method and which is better at detecting
Borrelia
-specific antibodies in sera from patients with stage I LD.
Replication of JC Virus DNA in the G144 Oligodendrocyte Cell Line Is Dependent Upon Akt
Authors: Peterson Jesse N. , Lin Brian , Shin Jong , Phelan Paul J. , Tsichlis Philip , Schwob James E. , Bullock Peter A.
Published: August 2017

Progressive multifocal leukoencephalopathy (PML) is an often-fatal demyelinating disease of the central nervous system. PML results when oligodendrocytes within immunocompromised individuals are infected with the human JC virus (JCV). We have identified an oligodendrocyte precursor cell line, termed G144, that supports robust levels of JCV DNA replication, a central part of the JCV life cycle. In addition, we have determined that JC virus readily infects G144 cells. Furthermore, we have determined that JCV DNA replication in G144 cells is stimulated by myristoylated (i.e., constitutively active) Akt and reduced by the Akt-specific inhibitor MK2206. Thus, this oligodendrocyte-based model system will be useful for a number of purposes, such as studies of JCV infection, establishing key pathways needed for the regulation of JCV DNA replication, and identifying inhibitors of this process.

IMPORTANCE
The disease progressive multifocal leukoencephalopathy (PML) is caused by the infection of particular brain cells, termed oligodendrocytes, by the JC virus. Studies of PML, however, have been hampered by the lack of an immortalized human cell line derived from oligodendrocytes. Here, we report that the G144 oligodendrocyte cell line supports both infection by JC virus and robust levels of JCV DNA replication. Moreover, we have established that the Akt pathway regulates JCV DNA replication and that JCV DNA replication can be inhibited by MK2206, a compound that is specific for Akt. These and related findings suggest that we have established a powerful oligodendrocyte-based model system for studies of JCV-dependent PML.
Ubiquitin Ligase WWP1 Interacts with Ebola Virus VP40 To Regulate Egress
Authors: Han Ziying , Sagum Cari A. , Takizawa Fumio , Ruthel Gordon , Berry Corbett T. , Kong Jing , Sunyer J. Oriol , Freedman Bruce D. , Bedford Mark T. , Sidhu Sachdev S. , Sudol Marius , Harty Ronald N.
Published: August 2017

Ebola virus (EBOV) is a member of the
Filoviridae
family and the cause of hemorrhagic fever outbreaks. The EBOV VP40 (eVP40) matrix protein is the main driving force for virion assembly and budding. Indeed, expression of eVP40 alone in mammalian cells results in the formation and budding of virus-like particles (VLPs) which mimic the budding process and morphology of authentic, infectious EBOV. To complete the budding process, eVP40 utilizes its PPXY L-domain motif to recruit a specific subset of host proteins containing one or more modular WW domains that then function to facilitate efficient production and release of eVP40 VLPs. In this report, we identified additional host WW-domain interactors by screening for potential interactions between mammalian proteins possessing one or more WW domains and WT or PPXY mutant peptides of eVP40. We identified the HECT family E3 ubiquitin ligase WWP1 and all four of its WW domains as strong interactors with the PPXY motif of eVP40. The eVP40-WWP1 interaction was confirmed by both peptide pulldown and coimmunoprecipitation assays, which also demonstrated that modular WW domain 1 of WWP1 was most critical for binding to eVP40. Importantly, the eVP40-WWP1 interaction was found to be biologically relevant for VLP budding since (i) small interfering RNA (siRNA) knockdown of endogenous WWP1 resulted in inhibition of eVP40 VLP egress, (ii) coexpression of WWP1 and eVP40 resulted in ubiquitination of eVP40 and a subsequent increase in eVP40 VLP egress, and (iii) an enzymatically inactive mutant of WWP1 (C890A) did not ubiquitinate eVP40 or enhance eVP40 VLP egress. Last, our data show that ubiquitination of eVP40 by WWP1 enhances egress of VLPs and concomitantly decreases cellular levels of higher-molecular-weight oligomers of eVP40. In sum, these findings contribute to our fundamental understanding of the functional interplay between host E3 ligases, ubiquitination, and regulation of EBOV VP40-mediated egress.

IMPORTANCE
Ebola virus (EBOV) is a high-priority, emerging human pathogen that can cause severe outbreaks of hemorrhagic fever with high mortality rates. As there are currently no approved vaccines or treatments for EBOV, a better understanding of the biology and functions of EBOV-host interactions that promote or inhibit viral budding is warranted. Here, we describe a physical and functional interaction between EBOV VP40 (eVP40) and WWP1, a host E3 ubiquitin ligase that ubiquitinates VP40 and regulates VLP egress. This viral PPXY-host WW domain-mediated interaction represents a potential new target for host-oriented inhibitors of EBOV egress.
High-Risk Alphapapillomavirus Oncogenes Impair the Homologous Recombination Pathway
Authors: Wallace Nicholas A. , Khanal Sujita , Robinson Kristin L. , Wendel Sebastian O. , Messer Joshua J. , Galloway Denise A.
Published: August 2017

Persistent high-risk genus human
Alphapapillomavirus
(HPV) infections cause nearly every cervical carcinoma and a subset of tumors in the oropharyngeal tract. During the decades required for HPV-associated tumorigenesis, the cellular genome becomes significantly destabilized. Our analysis of cervical tumors from four separate data sets found a significant upregulation of the homologous-recombination (HR) pathway genes. The increased abundance of HR proteins can be replicated in primary cells by expression of the two HPV oncogenes (E6 and E7) required for HPV-associated transformation. HPV E6 and E7 also enhanced the ability of HR proteins to form repair foci, and yet both E6 and E7 reduce the ability of the HR pathway to complete double-strand break (DSB) repair by about 50%. The HPV oncogenes hinder HR by allowing the process to begin at points in the cell cycle when the lack of a sister chromatid to serve as a homologous template prevents completion of the repair. Further, HPV E6 attenuates repair by causing RAD51 to be mislocalized away from both transient and persistent DSBs, whereas HPV E7 is only capable of impairing RAD51 localization to transient lesions. Finally, we show that the inability to robustly repair DSBs causes some of these lesions to be more persistent, a phenotype that correlates with increased integration of episomal DNA. Together, these data support our hypothesis that HPV oncogenes contribute to the genomic instability observed in HPV-associated malignancies by attenuating the repair of damaged DNA.

IMPORTANCE
This study expands the understanding of HPV biology, establishing a direct role for both HPV E6 and E7 in the destabilization of the host genome by blocking the homologous repair of DSBs. To our knowledge, this is the first time that both viral oncogenes were shown to disrupt this DSB repair pathway. We show that HPV E6 and E7 allow HR to initiate at an inappropriate part of the cell cycle. The mislocalization of RAD51 away from DSBs in cells expressing HPV E6 and E7 hinders HR through a distinct mechanism. These observations have broad implications. The impairment of HR by HPV oncogenes may be targeted for treatment of HPV
+
malignancies. Further, this attenuation of repair suggests HPV oncogenes may contribute to tumorigenesis by promoting the integration of the HPV genome, a common feature of HPV-transformed cells. Our data support this idea since HPV E6 stimulates the integration of episomes.
Grf10 and Bas1 Regulate Transcription of Adenylate and One-Carbon Biosynthesis Genes and Affect Virulence in the Human Fungal Pathogen Candida albicans
Authors: Wangsanut Tanaporn , Ghosh Anup K. , Metzger Peter G. , Fonzi William A. , Rolfes Ronda J.
Published: August 2017

Candida albicans
is a commensal and a common constituent of the human microbiota; however, it can become pathogenic and cause infections in both immunocompetent and immunocompromised people.
C. albicans
exhibits remarkable metabolic versatility as it can colonize multiple body sites as a commensal or pathogen. Understanding how
C. albicans
adapts metabolically to each ecological niche is essential for developing novel therapeutic approaches. Purine metabolism has been targeted pharmaceutically in several diseases; however, the regulation of this pathway has not been fully elucidated in
C. albicans
. Here, we report how
C. albicans
controls the AMP
de novo
biosynthesis pathway in response to purine availability. We show that the lack of the transcription factors Grf10 and Bas1 leads to purine metabolic dysfunction, and this dysfunction affects the ability of
C. albicans
to establish infections.
Preschool children who are frequent attenders in emergency departments: an observational study of associated demographics and clinical characteristics
Authors: Blair Mitch , Poots Alan J , Lim Valencia , Hiles Stephen , Greenfield Geva , Crehan Caroline , Kugler Beverley , Boreham Charlotte
Published: August 2017

Background

Unscheduled visits to emergency departments (ED) have increased in the UK in recent years. Children who are repeat attenders are relatively understudied.

Aims

To describe the sociodemographic and clinical characteristics of preschoolers who attend ED a large District General Hospital.

Method/study design

Observational study analysing routinely collected ED operational data. Children attending four or more visits per year were considered as ‘frequent attenders’. Poisson regression was used with demographic details (age, sex, ethnicity, sociodemographic status) to predict number of attendances seen in the year. We further analysed detailed diagnostic characteristics of a random sample of 10% of attendees.

Main findings

10 169 patients visited in the 12-month period with 16 603 attendances. 655 individuals attended on 3335 occasions. 6.4% of this population accounted for 20.1% of total visits. In the 10% sample, there were 304 attendances, and 69 (23%) had an underlying chronic long-standing illness (CLSI). This group were 2.4 times more likely to be admitted as inpatients compared with those without such conditions, median length of stay of 6.2 hours versus 2.5 hours (p=NS).

Conclusions

Frequent ED attenders fall broadly into two distinct clinical groups: those who habitually return with self-limiting conditions and those with or without exacerbation of underlying CLSI. Both groups may be amenable to both additional nursing and other forms of community support to enhance self-care and continuity of care. Further research is required to increase our understanding of specific individual family and health system factors that predict repeat attendance in this age group.
Tailored lamellar keratoplasty: a new technique
Authors: Solaimani Mohammad , Tabatabaei Seyed Ali , Fallah Tafti Zahra
Published: August 2017

We present a new method for treating complicated corneal gaps among patients who have previously undergone radial keratotomy (RK).

After complete healing of a fungal keratitis in a patient who has undergone RK, we removed the oedematous corneal sector and put anterior tailored segment of a corneal button previously used for Descemet stripping endothelial keratoplasty. The patient's best-corrected visual acuity reached to 20/20 6 months later. This technique will compensate for oedematous parts without putting a significant effect on other parts such as purse string sutures.