bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation tagging in indica rice identifies ribosomal proteins as potential targets for manipulation of water‐use efficiency and abiotic stress tolerance in plants
Authors: Moin Mazahar , Bakshi Achala , Saha Anusree , Udaya Kumar M. , Reddy Attipalli R. , Rao K. V. , Siddiq E. A. , Kirti P. B. 
Published: July 2016

AbstractWe have generated 3900 enhancer‐based activation‐tagged plants, in addition to 1030 stable Dissociator‐enhancer plants in a widely cultivated indica rice variety, BPT‐5204. Of them, 3000 were screened for water‐use efficiency (WUE) by analysing photosynthetic quantum efficiency and yield‐related attributes under water‐limiting conditions that identified 200 activation‐tagged mutants, which were analysed for flanking sequences at the site of enhancer integration in the genome. We have further selected five plants with low Δ13C, high quantum efficiency and increased plant yield compared with wild type for a detailed investigation. Expression studies of 18 genes in these mutants revealed that in four plants one of the three to four tagged genes became activated, while two genes were concurrently up‐regulated in the fifth plant. Two genes coding for proteins involved in 60S ribosomal assembly, RPL6 and RPL23A, were among those that became activated by enhancers. Quantitative expression analysis of these two genes also corroborated the results on activating–tagging. The high up‐regulation of RPL6 and RPL23A in various stress treatments and the presence of significant cis‐regulatory elements in their promoter regions along with the high up‐regulation of several of RPL genes in various stress treatments indicate that they are potential targets for manipulating WUE/abiotic stress tolerance.
Interaction of drought and ozone exposure on isoprene emission from extensively cultivated poplar
Authors: Yuan Xiangyang , Calatayud Vicent , Gao Feng , Fares Silvano , Paoletti Elena , Tian Yuan , Feng Zhaozhong 
Published: July 2016

AbstractThe combined effects of ozone (O3) and drought on isoprene emission were studied for the first time. Young hybrid poplars (clone 546, Populus deltoides cv. 55/56 x P. deltoides cv. Imperial) were exposed to O3 (charcoal‐filtered air, CF, and non‐filtered air +40 ppb, E‐O3) and soil water stress (well‐watered, WW, and mild drought, MD, one‐third irrigation) for 96 days. Consistent with light‐saturated photosynthesis (Asat), intercellular CO2 concentration (Ci) and chlorophyll content, isoprene emission depended on drought, O3, leaf position and sampling time. Drought stimulated emission (+38.4%), and O3 decreased it (−40.4%). Ozone increased the carbon cost per unit of isoprene emission. Ozone and drought effects were stronger in middle leaves (13th–15th from the apex) than in upper leaves (6th–8th). Only Asat showed a significant interaction between O3 and drought. When the responses were up‐scaled to the entire‐plant level, however, drought effects on total leaf area translated into around twice higher emission from WW plants in clean air than in E‐O3. Our results suggest that direct effects on plant emission rates and changes in total leaf area may affect isoprene emission from intensively cultivated hybrid poplar under combined MD and O3 exposure, with important feedbacks for air quality.
Tomato plants increase their tolerance to low temperature in a chilling acclimation process entailing comprehensive transcriptional and metabolic adjustments
Authors: Barrero‐Gil Javier , Huertas Raúl , Rambla José Luís , Granell Antonio , Salinas Julio 
Published: July 2016

AbstractLow temperature is a major environmental stress that seriously compromises plant development, distribution and productivity. Most crops are from tropical origin and, consequently, chilling sensitive. Interestingly, however, some tropical plants, are able to augment their chilling tolerance when previously exposed to suboptimal growth temperatures. Yet, the molecular and physiological mechanisms underlying this adaptive process, termed chilling acclimation, still remain practically unknown. Here, we demonstrate that tomato plants can develop a chilling acclimation response, which includes comprehensive transcriptomic and metabolic adjustments leading to increased chilling tolerance. More important, our results reveal strong resemblances between this response and cold acclimation, the process whereby plants from temperate regions raise their freezing tolerance after exposure to low, non‐freezing temperatures. Both chilling and cold acclimation are regulated by a similar set of transcription factors and hormones, and share common defence mechanisms, including the accumulation of compatible solutes, the mobilization of antioxidant systems and the rearrangement of the photosynthetic machinery. Nonetheless, we have found some important divergences that may account for the freezing sensitivity of tomato plants. The data reported in this manuscript should foster new research into the chilling acclimation response with the aim of improving tomato tolerance to low temperature.
Positive Returns and Equilibrium: Simultaneous Feedback Between Public Opinion and Social Policy
Authors: Breznau Nate 
Published: July 2016

AbstractThis paper pushes forward political research from across disciplines seeking to understand the linkages between public opinion and social policy in democracies. It considers the thermostatic and the increasing returns perspectives as pointing toward a potentially stable set of effects running between opinion and policy. Both theoretical perspectives argue that opinion and policy are reciprocally causal, feeding back on one another. This is a general argument found in opinion‐policy literatures. However, much empirical research claims to model “feedback” effects when actually using separate unidirectional models of opinion and policy. Only a small body of research addresses opinion‐policy endogeneity directly. In this paper I consider an opinion‐policy system with simultaneous feedback and without lags. I argue that there is a theoretical equilibrium in the relationship of opinion and policy underlying the otherwise cyclical processes that link them. Given that available cross‐national data are cross‐sectional and provide limited degrees of freedom, an ideal theoretical model must be somewhat constrained in order to arrive at empirically meaningful results. In this challenging and exploratory undertaking I hope to open up the possibility of a general system of effects between public opinion and social policy and how to model them in future research. I focus on social welfare policy as it is highly salient to public interests and a costly area of government budgets, making it an area of contentious policymaking. Social policy is also a major part of the thermostatic model of opinion and policy, which was recently extended to the cross‐national comparative context (Wlezien & Soroka, 2012) providing a critical predecessor to this paper because identification of equilibrium between public opinion and social policy in any given society is greatly enhanced through comparison with other societies. This counterfactual approach helps to identify opinion‐policy patterns that may not change much within societies, but can be seen as taking on discrete trajectories between societies.
The renal cortical collecting duct: a secreting epithelium?
Authors: Morla Luciana , Doucet Alain , Lamouroux Christine , Crambert Gilles , Edwards Aurélie 
Published: July 2016

Key points
The cortical collecting duct (CCD) plays an essential role in sodium homeostasis by fine‐tuning the amount of sodium that is excreted in the urine.
Ex vivo, the microperfused CCD reabsorbs sodium in the absence of lumen‐to‐bath concentration gradients.
In the present study, we show that, in the presence of physiological lumen‐to‐bath concentration gradients, and in the absence of endocrine, paracrine and neural regulation, the mouse CCD secretes sodium, which represents a paradigm shift.
This secretion occurs via the paracellular route, as well as a transcellular pathway that is energized by apical H+/K+‐ATPase type 2 pumps operating as Na+/K+ exchangers.
The newly identified transcellular secretory pathway represents a physiological target for the regulation of sodium handling and for anti‐hypertensive therapeutic agents.
AbstractIn vitro microperfusion experiments have demonstrated that cortical collecting ducts (CCDs) reabsorb sodium via principal and type B intercalated cells under sodium‐depleted conditions and thereby contribute to sodium and blood pressure homeostasis. However, these experiments were performed in the absence of the transepithelial ion concentration gradients that prevail in vivo and determine paracellular transport. The present study aimed to characterize Na+, K+ and Cl− fluxes in the mouse CCD in the presence of physiological transepithelial concentration gradients. For this purpose, we combined in vitro measurements of ion fluxes across microperfused CCDs of sodium‐depleted mice with the predictions of a mathematical model. When NaCl transport was inhibited in all cells, CCDs secreted Na+ and reabsorbed K+; Cl− transport was negligible. Removing inhibitors of type A and B intercalated cells increased Na+ secretion in wild‐type (WT) mice but not in H+/K+‐ATPase type 2 (HKA2) knockout mice. Further inhibition of basolateral NaCl entry via the Na+‐K+‐2Cl− cotransporter in type A intercalated cells reduced Na+ secretion in WT mice to the levels observed in HKA2−/− mice. With no inhibitors, WT mouse CCDs still secreted Na+ and reabsorbed K+. In vivo, HKA2−/− mice excreted less Na+ than WT mice after switching to a high‐salt diet. Taken together, our results indicate that type A intercalated cells secrete Na+ via basolateral Na+‐K+‐2Cl− cotransporters in tandem with apical HKA2 pumps. They also suggest that the CCD can mediate overall Na+ secretion, and that its ability to reabsorb NaCl in vivo depends on the presence of acute regulatory factors.
Identification of a New Benzimidazole Derivative as an Antiviral against Hepatitis C Virus
Authors: Vausselin Thibaut , Séron Karin , Lavie Muriel , Mesalam Ahmed Atef , Lemasson Matthieu , Belouzard Sandrine , Fénéant Lucie , Danneels Adeline , Rouillé Yves , Cocquerel Laurence , Foquet Lander , Rosenberg Arielle R. , Wychowski Czeslaw , Meuleman Philip , Melnyk Patricia , Dubuisson Jean 
Published: July 2016

ABSTRACT
Aminoquinolines and piperazines, linked or not, have been used successfully to treat malaria, and some molecules of this family also exhibit antiviral properties. Here we tested several derivatives of 4-aminoquinolines and piperazines for their activity against hepatitis C virus (HCV). We screened 11 molecules from three different families of compounds, and we identified anti-HCV activity in cell culture for six of them. Of these, we selected a compound (B5) that is currently ending clinical phase I evaluation for neurodegenerative diseases. In hepatoma cells, B5 inhibited HCV infection in a pangenotypic and dose-dependent manner, and its antiviral activity was confirmed in primary hepatocytes. B5 also inhibited infection by pseudoparticles expressing HCV envelope glycoproteins E1 and E2, and we demonstrated that it affects a postattachment stage of the entry step. Virus with resistance to B5 was selected by sequential passage in the presence of the drug, and reverse genetics experiments indicated that resistance was conferred mainly by a single mutation in the putative fusion peptide of E1 envelope glycoprotein (F291I). Furthermore, analyses of the effects of other closely related compounds on the B5-resistant mutant suggest that B5 shares a mode of action with other 4-aminoquinoline-based molecules. Finally, mice with humanized liver that were treated with B5 showed a delay in the kinetics of the viral infection. In conclusion, B5 is a novel interesting anti-HCV molecule that could be used to decipher the early steps of the HCV life cycle.

IMPORTANCE
In the last 4 years, HCV therapy has been profoundly improved with the approval of direct-acting antivirals in clinical practice. Nevertheless, the high costs of these drugs limit access to therapy in most countries. The present study reports the identification and characterization of a compound (B5) that inhibits HCV propagation in cell culture and is currently ending clinical phase I evaluation for neurodegenerative diseases. This molecule inhibits the HCV life cycle by blocking virus entry. Interestingly, after selection of drug-resistant virus, a resistance mutation in the putative fusion peptide of E1 envelope glycoprotein was identified, indicating that B5 could be used to further investigate the fusion mechanism. Furthermore, mice with humanized liver treated with B5 showed a delay in the kinetics of the viral infection. In conclusion, B5 is a novel interesting anti-HCV molecule that could be used to decipher the early steps of the HCV life cycle.
Human Papillomavirus E2 Protein: Linking Replication, Transcription, and RNA Processing
Authors: Graham Sheila V. 
Published: July 2016

ABSTRACT
The human papillomavirus (HPV) life cycle is tightly linked to differentiation of the infected epithelium. This means that viral proteins must exert control over epithelial gene expression in order to optimize viral production. The HPV E2 protein controls replication, transcription, and viral genome partitioning during the viral infectious life cycle. It consists of a nucleic acid-binding domain and a protein-protein interaction domain separated by a flexible serine and arginine-rich hinge region. Over the last few years, mounting evidence has uncovered an important new role for E2 in viral and cellular RNA processing. This Gem discusses the role of E2 in controlling the epithelial cellular environment and how E2 might act to coordinate late events in the viral replication cycle.
Risk of epilepsy in stroke patients receiving acupuncture treatment: a nationwide retrospective matched-cohort study
Authors: Weng Shu-Wen , Liao Chien-Chang , Yeh Chun-Chieh , Chen Ta-Liang , Lane Hsin-Long , Lin Jaung-Geng , Shih Chun-Chuan 
Published: July 2016

ObjectiveTo investigate the risk of epilepsy in stroke patients receiving and not receiving acupuncture treatment.DesignRetrospective cohort study.SettingThis study was based on Taiwan's National Health Insurance Research Database that included information on stroke patients hospitalised between 1 January 2000 and 31 December 2004.ParticipantsWe identified 42 040 patients hospitalised with newly diagnosed stroke who were aged 20 years and above.Primary and secondary outcome measuresWe compared incident epilepsy during the follow-up period until the end of 2009 in stroke patients who were and were not receiving acupuncture. The adjusted HRs and 95% CIs of epilepsy associated with acupuncture were calculated using multivariate Cox proportional hazard regression.ResultsStroke patients who received acupuncture treatment (9.8 per 1000 person-years) experienced a reduced incidence of epilepsy compared to those who did not receive acupuncture treatment (11.5 per 1000 person-years), with an HR of 0.74 (95% CI 0.68 to 0.80) after adjustment for sociodemographic factors and coexisting medical conditions. Acupuncture treatment was associated with a decreased risk of epilepsy, particularly among stroke patients aged 20–69 years. The log-rank test probability curve indicated that stroke patients receiving acupuncture treatment had a reduced probability of epilepsy compared with individuals who did not receive acupuncture treatment during the follow-up period (p<0.0001).ConclusionsStroke patients who received acupuncture treatment had a reduced risk of epilepsy compared with those not receiving acupuncture treatment. However, the protective effects associated with acupuncture treatment require further validation in prospective cohort studies.
Incidence, risk factors and the healthcare cost of falls postdischarge after elective total hip and total knee replacement surgery: protocol for a prospective observational cohort study
Authors: Hill Anne-Marie , Ross-Adjie Gail , McPhail Steven M , Monterosso Leanne , Bulsara Max , Etherton-Beer Christopher , Powell Sarah-Jayne , Hardisty Gerard 
Published: July 2016

IntroductionThe number of major joint replacement procedures continues to increase in Australia. The primary aim of this study is to determine the incidence of falls in the first 12 months after discharge from hospital in a cohort of older patients who undergo elective total hip or total knee replacement.Methods and analysesA prospective longitudinal observational cohort study starting in July 2015, enrolling patients aged ≥60 years who are admitted for elective major joint replacement (n=267 total hip replacement, n=267 total knee replacement) and are to be discharged to the community. Participants are followed up for 12 months after hospital discharge. The primary outcome measure is the rate of falls per thousand patient-days. Falls data will be collected by 2 methods: issuing a falls diary to each participant and telephoning participants monthly after discharge. Secondary outcomes include the rate of injurious falls and health-related quality of life. Patient-rated outcomes will be measured using the Oxford Hip or Oxford Knee score. Generalised linear mixed modelling will be used to examine the falls outcomes in the 12 months after discharge and to examine patient and clinical characteristics predictive of falls. An economic evaluation will be conducted to describe the nature of healthcare costs in the first 12 months after elective joint replacement and estimate costs directly attributable to fall events.Ethics and disseminationThe results will be disseminated through local site networks and will inform future services to support older people undergoing hip or knee joint replacement and also through peer-reviewed publications and medical conferences. This study has been approved by The University of Notre Dame Australia and local hospital human research ethics committees.Trial registration numberACTRN12615000653561; Pre-results.
Recognizing seasonal fluvial influence in ancient tidal deposits
Authors: McLean Annalize Q. , Wilson Brent 
Published: July 2016

Abstract
Seasonal changes in rainfall affect water and sediment discharges in fluvial systems. This is reflected within the rock record by changes in (1) the flow processes and structures created and (2) the composition and volume of sediment. This study demonstrates that high-resolution sedimentological studies of rhythmites in ancient tidal bar deposits reveal a seasonal fluvial influence. The rocks studied belong to the Plio-Pleistocene Erin Formation on Trinidad, deposited under tropical seasonal conditions in the fluvial–tidal transition zone and tidally dominated palaeoenvironments. Time-series and stratigraphic analyses were undertaken of two rock subsections separated by an erosional surface. Spring–neap, monthly and semi-annual cycles were identified within the deposits. Sand-rich and mud-rich couplets showed neap–spring cyclicity, with gradual transitions between flaser, wavy and lenticular bedding. Seasonal changes in fluvial discharge were recognized by minor scours that marked periods of relatively higher discharge. The content and distribution of organic material varied through the seasonally influenced cycle. Rare and dwarfed trace fossils and bioturbated beds also showed a periodic pattern, interpreted as representing changes in palaeoenvironmental conditions due to seasonal freshwater discharge. As a result, reservoirs containing similar deposits may have porosity and permeability variations with seasonal depositional periodicity.

Supplementary material:
The full set of measured time-series data is available at
https://doi.org/10.6084/m9.figshare.c.3283376
Remodeling of the Tumor Microenvironment Predicts Increased Risk of Cancer in Postmenopausal Women: The Prospective Epidemiologic Risk Factor (PERF I) Study
Authors: Bager Cecilie L. , Willumsen Nicholas , Kehlet Stephanie N. , Hansen Henrik B. , Bay-Jensen Anne-Christine , Leeming Diana J. , Dragsbæk Katrine , Neergaard Jesper Skov , Christiansen Claus , Høgdall Estrid , Karsdal Morten 
Published: July 2016

Abstract
Background: An altered tumor microenvironment is one of the earliest signs of cancer and an important driver of the disease. We have seen previously that biomarkers reflecting tumor microenvironment modifications, such as matrix metalloproteinase (MMP)-degraded type 1 collagen (C1M), MMP-degraded type IV collagen (C4M), and citrullinated and MMP-degraded vimentin (VICM), were higher in the serum of cancer patients than in healthy controls. However, it is not known if these biomarkers could predict an increased risk of cancer. The aim of this study was to investigate whether C1M, C4M, and VICM were elevated prior to diagnosis of solid cancers in a large prospective study.
Methods: Between 1999 and 2001, 5,855 postmenopausal Danish women ages 48 to 89 years enrolled in the Prospective Epidemiologic Risk Factor study. Baseline demographics and serum were collected at the time of registration. Follow up cancer diagnoses were obtained from the Danish Cancer Registry in 2014. Serum C1M, C4M, and VICM levels were measured by competitive ELISAs.
Results: A total of 881 women were diagnosed with solid cancers after baseline. C1M, C4M, and VICM levels were significantly elevated in women diagnosed less than 1 year after baseline. C1M and VICM, but not C4M, were independent predictors of increased risk of cancer.
Conclusion: C1M, C4M, and VICM are elevated prior to cancer diagnosis. C1M and VICM are both independent predictors of increased cancer risk.
Impact: C1M and VICM are predictors for increased risk of cancer. Cancer Epidemiol Biomarkers Prev; 25(9); 1348–55. ©2016 AACR.
Antihyperglycemic Medication Use Among Medicare Beneficiaries With Heart Failure, Diabetes Mellitus, and Chronic Kidney Disease
Authors: Patel Priyesh A. , Liang Li , Khazanie Prateeti , Hammill Bradley G. , Fonarow Gregg C. , Yancy Clyde W. , Bhatt Deepak L. , Curtis Lesley H. , Hernandez Adrian F. 
Published: July 2016

Background—
Diabetes mellitus, heart failure (HF), and chronic kidney disease are common comorbidities, but overall use and safety of antihyperglycemic medications (AHMs) among patients with these comorbidities are poorly understood.

Methods and Results—

Using Get With the Guidelines-Heart Failure and linked Medicare Part D data, we assessed AHM use within 90 days of hospital discharge among HF patients with diabetes mellitus discharged from Get With the Guidelines-Heart Failure hospitals between January 1, 2006, and October 1, 2011. We further summarized use by renal function and assessed renal contraindicated AHM use for patients with estimated glomerular filtration rate <30 mL/min/1.73m
2
. Among 8791 patients meeting inclusion criteria, the median age was 77 (interquartile range 71–83), 62.3% were female, median body mass index was 29.7 (interquartile range 25.5–35.3), median hemoglobin A1c was 6.8 (interquartile range 6.2–7.8), and 34% had ejection fraction <40%. 74.9% of patients filled a prescription for an AHM, with insulin (39.5%), sulfonylureas (32.4%), and metformin (17%) being the most commonly used AHMs. Insulin use was higher and sulfonylurea/metformin use was lower among patients with lower renal function classes. Among 1512 patients with estimated glomerular filtration rate <30 mL/min/1.73m
2
, 35.4% filled prescriptions for renal contraindicated AHMs per prescribing information, though there was a trend toward lower renal contraindicated AHM use over time (Cochran–Mantel–Haenszel row-mean score test
P
=0.048). Although use of other AHMs was low overall, thiazolidinediones were used in 6.6% of HF patients, and dipeptidyl peptidase-4 inhibitors were used in 5.1%, with trends for decreasing thiazolidinedione use and increased dipeptidyl peptidase-4 inhibitor use over time (
P
<0.001).

Conclusions—
Treatment of diabetes mellitus in patients with HF and chronic kidney disease is complex, and these patients are commonly treated with renal contraindicated AHMs, including over 6% receiving a thiazolidinedione, despite known concerns regarding HF. More research regarding safety and efficacy of various AHMs among HF patients is needed.