bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural diversity in daily rhythms of gene expression contributes to phenotypic variation
Authors: de Montaigu Amaury , Giakountis Antonis , Rubin Matthew , Tóth Réka , Cremer Frédéric , Sokolova Vladislava , Porri Aimone , Reymond Matthieu , Weinig Cynthia , Coupland George
Published: December 2014

Significance

Daily rhythms of gene expression ensure that biological processes occur at the optimal time of day. In plants, temporally regulated processes include traits of ecological and agricultural importance, and understanding how changes in daily rhythms of expression modify such traits has broad implications. We find that natural genetic variation can accurately modify temporal gene expression waveforms during the day by influencing light signaling pathways, rather than circadian rhythms. We further show that changes in transcriptional patterns induced by natural alleles are sufficient to affect downstream molecular outputs and cause phenotypic diversity. Such natural alleles could provide an advantage by adjusting the activity of temporally regulated processes while avoiding the pleiotropic effects associated with severe disruptions of the circadian system.
Transient assembly of F-actin on the outer mitochondrial membrane contributes to mitochondrial fission
Authors: Li Sunan , Xu Shan , Roelofs Brian A. , Boyman Liron , Lederer W. Jonathan , Sesaki Hiromi , Karbowski Mariusz
Published: December 2014

In addition to established membrane remodeling roles in various cellular locations, actin has recently emerged as a participant in mitochondrial fission. However, the underlying mechanisms of its participation remain largely unknown. We report that transient de novo F-actin assembly on the mitochondria occurs upon induction of mitochondrial fission and F-actin accumulates on the mitochondria without forming detectable submitochondrial foci. Impairing mitochondrial division through Drp1 knockout or inhibition prolonged the time of mitochondrial accumulation of F-actin and also led to abnormal mitochondrial accumulation of the actin regulatory factors cortactin, cofilin, and Arp2/3 complexes, suggesting that disassembly of mitochondrial F-actin depends on Drp1 activity. Furthermore, down-regulation of actin regulatory proteins led to elongation of mitochondria, associated with mitochondrial accumulation of Drp1. In addition, depletion of cortactin inhibited Mfn2 down-regulation– or FCCP-induced mitochondrial fragmentation. These data indicate that the dynamic assembly and disassembly of F-actin on the mitochondria participates in Drp1-mediated mitochondrial fission.
A protein complex containing Epo1p anchors the cortical endoplasmic reticulum to the yeast bud tip
Authors: Neller Joachim , Dünkler Alexander , Rösler Reinhild , Johnsson Nils
Published: December 2014

The cortical endoplasmic reticulum (cER) of yeast underlies the plasma membrane (PM) at specific contact sites to enable a direct transfer of information and material between both organelles. During budding, directed movement of cER to the young bud followed by subsequent anchorage at its tip ensures the faithful inheritance of this organelle. The ER membrane protein Scs2p tethers the cER to the PM and to the bud tip through so far unknown receptors. We characterize Epo1p as a novel member of the polarisome that interacts with Scs2p exclusively at the cell tip during bud growth and show that Epo1p binds simultaneously to the Cdc42p guanosine triphosphatase–activating protein Bem3p. Deletion of EPO1 or deletion of BEM3 in a polarisome-deficient strain reduces the amount of cER at the tip. This analysis therefore identifies Epo1p as a novel and important component of the polarisome that promotes cER tethering at sites of polarized growth.
Conditional symbolic analysis detects nonlinear influences of respiration on cardiovascular control in humans
Authors: Porta Alberto , Marchi Andrea , Bari Vlasta , Heusser Karsten , Tank Jens , Jordan Jens , Barbic Franca , Furlan Raffaello
Published: December 2014

We propose a symbolic analysis framework for the quantitative characterization of complex dynamical systems. It allows the description of the time course of a single variable, the assessment of joint interactions and an analysis triggered by a conditioning input. The framework was applied to spontaneous variability of heart period (HP), systolic arterial pressure (SAP) and integrated muscle sympathetic nerve activity (MSNA) with the aim of characterizing cardiovascular control and nonlinear influences of respiration at rest in supine position, during orthostatic challenge induced by 80° head-up tilt (TILT) and about 3 min before evoked pre-syncope signs (PRESY). The approach detected (i) the exaggerated sympathetic modulation and vagal withdrawal from HP variability and the increased presence of fast MSNA variability components during PRESY compared with TILT; (ii) the increase of the SAP–HP coordination occurring at slow temporal scales and a decrease of that occurring at faster time scales during PRESY compared with TILT; (iii) the reduction of the coordination between fast MSNA and SAP patterns during TILT and PRESY; (iv) the nonlinear influences of respiration leading to an increased likelihood to observe the abovementioned findings during expiration compared with inspiration one. The framework provided simple, quantitative indexes able to distinguish experimental conditions characterized by different states of the autonomic nervous system and to detect the early signs of a life threatening situation such as postural syncope.
PLATONSQUEEZE: a tool for the calculation of the disordered solvent contribution to the calculated structure factors
Authors: Spek Anthony L.
Published: December 2014

The completion of a crystal structure determination is often hampered by the presence of embedded solvent molecules or ions that are seriously disordered. Their contribution to the calculated structure factors in the least-squares refinement of a crystal structure has to be included in some way. Traditionally, an atomistic solvent disorder model is attempted. Such an approach is generally to be preferred, but it does not always lead to a satisfactory result and may even be impossible in cases where channels in the structure are filled with continuous electron density. This paper documents the SQUEEZE method as an alternative means of addressing the solvent disorder issue. It conveniently interfaces with the 2014 version of the least-squares refinement programSHELXL[Sheldrick (2015).Acta Cryst.C71. In the press] and other refinement programs that accept externally provided fixed contributions to the calculated structure factors. ThePLATONSQUEEZE tool calculates the solvent contribution to the structure factors by back-Fourier transformation of the electron density found in the solvent-accessible region of a phase-optimized difference electron-density map. The actual least-squares structure refinement is delegated to, for example,SHELXL. The current versions ofPLATONSQUEEZE andSHELXLnow address several of the unnecessary complications with the earlier implementation of the SQUEEZE procedure that were a necessity because least-squares refinement with the now supersededSHELXL97program did not allow for the input of fixed externally provided contributions to the structure-factor calculation. It is no longer necessary to subtract the solvent contribution temporarily from the observed intensities to be able to useSHELXLfor the least-squares refinement, since that program now accepts the solvent contribution from an external file (.fab file) if the ABIN instruction is used. In addition, many twinned structures containing disordered solvents are now also treatable by SQUEEZE. The details of a SQUEEZE calculation are now automatically included in the CIF archive file, along with the unmerged reflection data. The current implementation of the SQUEEZE procedure is described, and discussed and illustrated with three examples. Two of them are based on the reflection data of published structures and one on synthetic reflection data generated for a published structure.
Personality, plasticity and predation: linking endocrine and behavioural reaction norms in stickleback fish
Authors: Fürtbauer Ines , Pond Alice , Heistermann Michael , King Andrew J.
Published: December 2014

Predation plays a fundamental role in evolutionary processes, driving changes in prey morphology, physiology and behaviour. With organisms being increasingly exposed to rapid environmental changes, there is growing interest in understanding individual phenotypic plasticity in response to changes in predation pressure.

Behavioural and physiological responses to predator exposure are of particular interest as differences in predation pressure are often reflected in correlated suites of behavioural and hormonal profiles across populations. Within populations, the association between endocrine profiles and behaviour is less understood and often lacking.

Adopting a reaction norm approach and a repeated measures design, we assessed within‐population effects of changes in perceived predation risk on endocrinology and behaviour in three‐spined sticklebacks (Gasterosteus aculeatus). We repeatedly exposed subjects to a robotic model predator and assessed their behavioural response. The fish showed consistent behavioural profiles and were less active and shyer when predation risk was higher.

Using non‐invasive waterborne hormone analysis, we assessed basal cortisol as well as the cortisol response to changes in predation risk. Individuals showed significantly higher cortisol levels following exposure to the model predator. Individual post‐predator exposure cortisol was repeatable but unrelated to behavioural responses. Accounting for between versus within‐subject effects, we found that basal cortisol and shyness were positively related within individuals, that is individuals overall were shyer on days they had higher cortisol levels. We also tested if basal testosterone predicted risky behaviour and found no evidence for this hypothesis.

No individual differences in hormonal or behavioural responses to changes in predation risk were found, suggesting that individuals are not constrained by their personalities in their ability to cope with a potentially harmful threat.

Overall, we show that individuals of different personalities are equally ‘flexible’ in their response to changes in predation pressure. Our study offers novel insight into consistent individual differences and plasticity in hormones and behaviour as well as their interplay within populations. Future studies should assess the applicability of these findings to other changes in the environment, as well as the effects of social context on endocrine and behavioural reaction norms.
Temperature‐induced recruitment pulses of Arctic dwarf shrub communities
Authors: Büntgen Ulf , Hellmann Lena , Tegel Willy , Normand Signe , Myers‐Smith Isla , Kirdyanov Alexander V. , Nievergelt Daniel , Schweingruber Fritz H.
Published: December 2014

The effects of climate change on Arctic ecosystems can range between various spatiotemporal scales and may include shifts in population distribution, community composition, plant phenology, primary productivity and species biodiversity. The growth rates and age structure of tundra vegetation as well as its response to temperature variation, however, remain poorly understood because high‐resolution data are limited in space and time.

Anatomical and morphological stem characteristics were recorded to assess the growth behaviour and age structure of 871 dwarf shrubs from 10 species at 30 sites in coastal East Greenland at ˜70°N. Recruitment pulses were linked with changes in mean annual and summer temperature back to the 19th century, and a literature review was conducted to place our findings in a pan‐Arctic context.

Low cambial activity translates into estimated average/maximum plant ages of 59/204 years, suggesting relatively small turnover rates and stable community composition. Decade‐long changes in the recruitment intensity were found to lag temperature variability by 2 and 6 years during warmer and colder periods, respectively (r = 0.851961–2000 and 1881–1920).

Synthesis. Our results reveal a strong temperature dependency of Arctic dwarf shrub reproduction, a high vulnerability of circumpolar tundra ecosystems to climatic changes, and the ability of evaluating historical vegetation dynamics well beyond the northern treeline. The combined wood anatomical and plant ecological approach, considering insights from micro‐sections to community assemblages, indicates that model predictions of rapid tundra expansion (i.e. shrub growth) following intense warming might underestimate plant longevity and persistence but overestimate the sensitivity and reaction time of Arctic vegetation.
Club drug use and associated high‐risk sexual behaviour in six provinces in China
Authors: Bao Yan‐Ping , Liu Zhi‐Min , Li Jian‐Hua , Zhang Rui‐Min , Hao Wei , Zhao Min , Shi Jie , McGoogan Jennifer M. , Lu Lin
Published: December 2014

Aim

To investigate the characteristics of the different club drugs and associated high‐risk sexual behaviours in China.

Design

Multicentre cross‐sectional study.

Setting

Drug Detoxification and Rehabilitation Centres in six provinces, China.

Participants

A total of 1434 eligible club drug users were included.

Measurements

Participants were investigated by trained interviewers using a self‐designed structured questionnaire to collect information on club drug use and associated behaviours.

Findings

Methamphetamine was the most commonly abused drug in participants (73.92%), who used it in their or their friends' homes by non‐injection for the purpose of feeling euphoria. Among participants with sexual behaviours after club drug use, 75.21% reported having engaged in sex with multiple partners after club drug use during the past year and 79.84% had unprotected sex after using club drug during the past year. A two‐level logistic model showed that male gender [adjusted odds ratio (AOR) = 7.14; 95% confidence interval (CI) = 4.17–12.5], unmarried (AOR = 1.71, 95% CI = 1.04–2.79), long duration of club drug use during their life‐time (AOR = 1.76, 95% CI = 1.28–2.42) and severe acute intoxication after using club drugs during the past year (AOR = 2.11, 95% CI = 1.07–4.15) were independent risk factors of multiple sex partners during the past year. Another two‐level model showed that the club drug users who were female (AOR = 1.79, 95% CI = 1.03–3.11) and had polydrug use during their lifetime (AOR = 1.55, 95% CI = 1.01–2.34) had more risk for unprotected sex during the past year than without these characteristics.

Conclusion

High‐risk sexual behaviours are common among club drug users in China. The prevention and intervention of club drug use could decrease the risk of sexual behaviours which further prevent HIV transmission and other sexually transmitted infections in China.
A cost‐effective analysis of fibrin sealants versus no sealant following open right hemihepatectomy for colorectal liver metastases
Authors: Pandanaboyana Sanjay , Bell Richard , Shah Nehal , Lodge J. Peter A. , Hidalgo Ernest , Toogood Giles J. , Prasad K. Raj
Published: December 2014

Background

There is paucity of data regarding the cost‐effectiveness of fibrin sealants during liver surgery. This study aimed to assess the cost‐effectiveness of fibrin sealants following right hemihepatectomy for colorectal liver metastases.

Method

A prospectively maintained database between 2004 and 2013 was reviewed to identify patients who underwent a right hemihepatectomy with and without fibrin sealant application. Perioperative and post‐operative outcomes were analysed to assess its cost‐effectiveness.

Results

One hundred and sixty‐three right hemihepatectomies were performed, of which 79 were in the fibrin sealant treatment group and 84 were in the no sealant group. No difference was seen between fibrin sealant and no sealant with regard to bile leak (P = 0.366), intra‐abdominal collections (P = 0.200) and overall post‐operative complications (P = 0.480). Operating costs were significantly cheaper in the no sealant group (P = 0.010). There was no difference seen in median post‐operative stay between fibrin sealant versus no treatment (8 versus 9 days, P = 0.327), median total bed cost (£3900 versus £4300, P = 0.400), mean transfusion cost per patient (P = 0.201) and overall cost (£6706.15 versus £6555.80, P = 0.792).

Conclusion

Fibrin sealant application to cut surface during liver surgery confers no cost benefit and their routine use may not be recommended.
Trainee underperformance: a guide to achieving resolution
Authors: Rashid Prem , Grills Richard , Kuan Melvyn , Klein Deborah
Published: December 2014

Background

Underperformance and the disharmony it can cause are not commonly faced by trainees. However, when it occurs, a process to recognize and manage the issues compassionately must be put in place.

Method

A literature review was undertaken to outline processes and themes in addressing and resolving these types of issues. A PubMed search using ‘surgical underperformance’ and ‘remedial teaching’ was used as a broad template to find papers that illustrated key concepts. One thousand four hundred and fifteen papers were identified. In papers where the titles were in line with the stated topic, 294 abstracts were reviewed. Key papers were used to develop themes. Additional cross‐referenced papers were also included where relevant.

Results

There can be a variety of reasons for trainee underperformance. The root cause is not always clear. Disharmony can result in a surgical unit during this time. The involved trainee as well as the members of the clinical unit may experience a variety of stressors. A systematic process of management can be used to evaluate the situation and bring some resolution to difficulties in working relationships.

Conclusion

Early constructive intervention improves outcomes. There should be a process to systematically and compassionately resolve underlying issues. This paper outlines the disharmony that can result from trainee underperformance and offers guidance for resolution to those involved.
Themed section
Authors: Christie M J , Connor M , Traynor J R
Published: December 2014

Linked Articles

This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2
Inherited disorders of gamma‐aminobutyric acid metabolism and advances in ALDH5A1 mutation identification
Authors: Pearl Phillip L , Parviz Mahsa , Vogel Kara , Schreiber John , Theodore William H , Gibson K Michael
Published: December 2014

Inherited disorders of gamma‐aminobutyric acid (GABA) metabolism include succinic semialdehyde dehydrogenase (SSADH) and gamma‐aminobutyric acid transaminase (GABA‐T) deficiencies. The clinical features, pathophysiology, diagnosis, and management of both, and an updated list of mutations in the ALDH5A1 gene, which cause SSADH deficiency, are discussed. A database of 112 individuals (71 children and adolescents, and 41 adults) indicates that developmental delay and hypotonia are the most common symptoms arising from SSADH deficiency. Furthermore, epilepsy is present in two‐thirds of SSADH‐deficient individuals by adulthood. Research with murine genetic models and human participants, using [11C] flumazenil positron emission tomography (FMZ‐PET) and transcranial magnetic stimulation, have led to therapeutic trials, and the identification of additional disruptions to GABA metabolism. Suggestions for new therapies have arisen from findings of GABAergic effects on autophagy, with enhanced activation of the mammalian target of rapamycin (mTOR) pathway. Details of known pathogenic mutations in the ALDH5A1 gene, three of which have not previously been reported, are summarized here. Investigations into disorders of GABA metabolism provide fundamental insights into the mechanisms underlying epilepsy, and support the importance of developing biomarkers and clinical trials. Comprehensive definition of phenotypes arising as a result of deficiencies in both SSADH and GABA‐T may increase our understanding of the neurophysiological consequences of a hyper‐GABAergic state.
Sleep in cluster headache − beyond a temporal rapid eye movement relationship?
Authors: Barloese M. C. J. , Jennum P. J. , Lund N. T. , Jensen R. H.
Published: December 2014

Background and purpose

Cluster headache (CH) is a primary headache disorder characterized by severe attacks of unilateral pain following a chronobiological pattern. There is a close connection with sleep as most attacks occur during sleep. Hypothalamic involvement and a particular association with rapid eye movement (REM) sleep have been suggested. Sleep in a large, well‐characterized population of CH patients was investigated.

Methods

Polysomnography (PSG) was performed on two nights in 40 CH patients during active bout and one night in 25 age, sex and body mass index matched controls in hospital. Macrostructure and other features of sleep were analyzed and related to phenotype. Clinical headache characterization was obtained by semi‐structured interview.

Results

Ninety‐nine nights of PSG were analyzed. Findings included a reduced percentage of REM sleep (17.3% vs. 23.0%, P = 0.0037), longer REM latency (2.0 vs. 1.2 h, P = 0.0012) and fewer arousals (7.34 vs. 14.1, P = 0.003) in CH patients. There was no difference in prevalence of sleep apnea between patients (38%) and matched controls (32%, P = 0.64) although the apnea index in patients was numerically higher (mean apnea−hypopnea index 10.75 vs. 4.93). No temporal association between nocturnal attacks (n = 45) and particular sleep stages was observed.

Conclusions

To date, this is the largest study of sleep in CH. It is demonstrated that REM sleep is affected which is in line with our current understanding of CH and hypothalamic involvement in the regulation of this sleep stage. Further, fewer arousals were found in CH patients but no association between apnea events or specific sleep stages. The findings support a central role of the hypothalamus and arousal systems in CH.
Clinical treatment and prognosis of equine odontoclastic tooth resorption and hypercementosis
Authors: Lorello O. , Foster D. L. , Levine D. G. , Boyle A. , Engiles J. , Orsini J. A.
Published: December 2014

Reasons for performing study

Equine odontoclastic tooth resorption and hypercementosis is an infrequent and underdiagnosed form of severe dental disease in horses that can affect quality of life. The study was performed to compare the clinical, radiographic, histological and prognostic findings specific to equine odontoclastic tooth resorption and hypercementosis in horses. Removal of affected teeth is currently the best treatment.

Objectives

The goals are to report salient clinical and histological features of the disease and its management in a case series describing an under‐reported syndrome in horses and the long‐term prognosis.

Study design

Retrospective case series.

Methods

Medical records from New Bolton Center, University of Pennsylvania from January 2000 to December 2012 were reviewed from horses that had a diagnosis of ‘cementoma’ or ‘hypercementosis’ and any associated dental‐related diagnosis affecting the teeth and oral cavity. Radiographic, surgical and histological reports were collated and the clinical cases compared and tabulated to provide a better description of the equine disease.

Results

A total of 18 cases were identified, 17 of which were geldings and one of which was a nonbreeding stallion; no mares had the disease. The mean age at diagnosis was 24 years, with a range of 17–29 years. There was no breed predilection, and varied clinical signs relating to the mouth were found. Some teeth involved had only radiographic changes of disease and not gross clinical evidence. The mandibular incisors were generally affected earlier than the maxillary incisors, but the disease is progressive, and eventually, all of the incisors and sometimes the canines are involved. No premolars or molars were affected in this case series.

Conclusions

Based on this case series, all teeth, and particularly the incisors, should be examined for signs of gingivitis and hypercementosis and subsequently radiographed for an early diagnosis and management. When compared with our hospital population, older geldings were more likely to be affected with cementoma formation and its accompanying resorptive process. Removal of clinically and radiographically affected teeth carries a good prognosis for improved quality of life.
Extensive metazoan reefs from the Ediacaran Nama Group, Namibia: the rise of benthic suspension feeding
Authors: Wood R. , Curtis A.
Published: December 2014

We describe new, ecologically complex reef types from the Ediacaran Nama Group, Namibia, dated at ~548 million years ago (Ma), where the earliest known skeletal metazoans,Cloudina riemkeaeandNamacalathus, formed extensive reefs up to 20 m in height and width.C. riemkeaeformed densely aggregating assemblages associated with microbialite and thrombolite, each from 30 to 100 mm high, which successively colonised former generations to create stacked laminar or columnar reef frameworks.C. riemkeaeindividuals show budding, multiple, radiating attachment sites and cementation between individuals. IsolatedNamacalathuseither intergrew withC. riemkeaeor formed dense, monospecific aggregations succeedingC. riemkeaeframeworks, providing a potential example of environmentally mediated ecological succession.CloudinaandNamacalathusalso grow cryptically, either as pendent aggregations from laminar crypt ceilings in microbial framework reefs or as clusters associated with thrombolite attached to neptunian dyke walls. These reefs are notable for their size, exceeding that of the succeeding Lower Cambrian archaeocyath–microbial communities. The repeated colonisation shown byC. riemkeaeof former assemblages implies philopatric larval aggregation to colonise limited favourable substrates. As such, not only were skeletal metazoans more important contributors to reef building in the Ediacaran, but there were also more variable reef types with more complex ecologies, than previously thought. Such an abundance of inferred suspension feeders with biomineralised skeletons indicates the efficient exploitation of new resources, more active carbon removal with a strengthened energy flow between planktic and benthic realms, and the rise of biological control over benthic carbonate production. These mark the prelude to the Cambrian Explosion and the modernisation of the global carbon cycle.
Greater deciduous shrub abundance extends tundra peak season and increases modeled net CO2 uptake
Authors: Sweet Shannan K. , Griffin Kevin L. , Steltzer Heidi , Gough Laura , Boelman Natalie T.
Published: December 2014

Satellite studies of the terrestrial Arctic report increased summer greening and longer overall growing and peak seasons since the 1980s, which increases productivity and the period of carbon uptake. These trends are attributed to increasing air temperatures and reduced snow cover duration in spring and fall. Concurrently, deciduous shrubs are becoming increasingly abundant in tundra landscapes, which may also impact canopy phenology and productivity. Our aim was to determine the influence of greater deciduous shrub abundance on tundra canopy phenology and subsequent impacts on net ecosystem carbon exchange (NEE) during the growing and peak seasons in the arctic foothills region of Alaska. We compared deciduous shrub‐dominated and evergreen/graminoid‐dominated community‐level canopy phenology throughout the growing season using the normalized difference vegetation index (NDVI). We used a tundra plant‐community‐specific leaf area index (LAI) model to estimate LAI throughout the green season and a tundra‐specific NEE model to estimate the impact of greater deciduous shrub abundance and associated shifts in both leaf area and canopy phenology on tundra carbon flux. We found that deciduous shrub canopies reached the onset of peak greenness 13 days earlier and the onset of senescence 3 days earlier compared to evergreen/graminoid canopies, resulting in a 10‐day extension of the peak season. The combined effect of the longer peak season and greater leaf area of deciduous shrub canopies almost tripled the modeled net carbon uptake of deciduous shrub communities compared to evergreen/graminoid communities, while the longer peak season alone resulted in 84% greater carbon uptake in deciduous shrub communities. These results suggest that greater deciduous shrub abundance increases carbon uptake not only due to greater leaf area, but also due to an extension of the period of peak greenness, which extends the period of maximum carbon uptake.
The abiotic and biotic factors limiting establishment of predatory fishes at their expanding northern range boundaries in Ontario, Canada
Authors: Alofs Karen M. , Jackson Donald A.
Published: December 2014

There is a poor understanding of the importance of biotic interactions in determining species distributions with climate change. Theory from invasion biology suggests that the success of species introductions outside of their historical ranges may be either positively (biotic acceptance) or negatively (biotic resistance) related to native biodiversity. Using data on fish community composition from two survey periods separated by approximately 28 years during which climate was warming, we examined the factors influencing the establishment of three predatory centrarchids: Smallmouth Bass (Micropterus dolomieu), Largemouth Bass (M. salmoides), and Rock Bass (Ambloplites rupestris) in lakes at their expanding northern range boundaries in Ontario. Variance partitioning demonstrated that, at a regional scale, abiotic factors play a stronger role in determining the establishment of these species than biotic factors. Pairing lakes within watersheds where each species had established with lakes sharing similar abiotic conditions where the species had not established revealed both positive and negative relationships between the establishment of centrarchids and the historical presence of other predatory species. The establishment of these species near their northern range boundaries is primarily determined by abiotic factors at a regional scale; however, biotic factors become important at the lake‐to‐lake scale. Studies of exotic species invasions have previously highlighted how spatial scale mediates the importance of abiotic vs. biotic factors on species establishment. Our study demonstrates how concepts from invasion biology can inform our understanding of the factors controlling species distributions with changing climate.
Indirect cytocompatibility of a low‐concentration hydrogen peroxide bleaching gel to odontoblast‐like cells
Authors: Soares D. G. , Marcomini N. , Basso F. G. , Pansani T. N. , Hebling J. , de Souza Costa C. A.
Published: December 2014

Aim

To assess the initial cytotoxicity and the late phenotype marker expression of odontoblast‐like cells (MDPC‐23) subjected to less aggressive in‐office bleaching therapies.

Methodology

A 17.5% hydrogen peroxide (H2O2) gel was applied for 45, 15 or 5 min to enamel/dentine discs adapted to trans‐wells positioned over cultured MDPC‐23 cells. No treatment was performed on the negative control. Immediately after bleaching, the cell viability, gene expression of inflammatory mediators and quantification of H2O2 diffusion were evaluated. The ALP activity, DSPP and DMP‐1 gene expression and mineralized nodule deposition (MND) were assessed at 7, 14 or 21 days post‐bleaching and analysed statistically with Mann–Whitney U‐tests (α = 5%).

Results

H2O2 diffusion, proportional to treatment time, was observed in all bleached groups. Reductions of approximately 31%, 21% and 13% in cell viability were observed for the 45‐, 15‐ and 5‐min groups, respectively. This reduction was significant (P < 0.05) for the 45‐ and 15‐min groups, which also presented significant (P < 0.05) over‐expression of inflammatory mediators. The 45‐min group was associated with significant (P < 0.05) reductions in DMP‐1/DSPP expression at all periods, relative to control. The ALP activity and MND were reduced only in initial periods. The 15‐min group had less intense reduction of all markers, with no difference to control at 21 days.

Conclusions

The 17.5% H2O2 applied to tooth specimens for 5 min caused no alteration in the odontoblast‐like cells. When this gel was applied for 45 or 15 min, a slight cytotoxicity, associated with alterations in phenotypic markers, was observed. However, cells were able to recover their functions up to 21 days post‐bleaching.
Statistical Analysis Plan for the ‘Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke’ (TARDIS) Trial
Authors: Bath Philip M. W. , Robson Katie , Woodhouse Lisa J. , Sprigg Nikola , Dineen Robert , Pocock Stuart
Published: December 2014

Rationale

Antiplatelet agents such as aspirin, clopidogrel and dipyridamole are effective in reducing the risk of recurrence after a stroke. Importantly, the risk of recurrence is highest immediately after the index event while antiplatelets cause bleeding.

Aims and/or hypothesis

The ‘Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke’ (TARDIS) trial is testing whether short-term intensive antiplatelet therapy is safe and effective in reducing the early risk of recurrence as compared with standard guideline-based therapy.

Design

TARDIS is an international multicenter prospective randomized open-label blinded-end-point trial, with funding from the UK Health Technology Assessment program. Patients with acute ischemic stroke or transient ischemic attack are randomized within 48 h to intensive/triple antiplatelet therapy or guideline antiplatelets taken for one-month. Patients or relatives give written informed (proxy) consent and all sites have research ethics approval. Analyses will be done by intention-to-treat.

Study Outcome

The primary outcome is shift in stroke recurrent events and their severity, assessed using the modified Rankin Scale, at three-months.

Discussion

This paper and attachment describe the trial's statistical analysis plan, as developed from the protocol during recruitment and prior to unblinding of data. The statistical analysis plan contains design and methods for analyses, and unpopulated tables and figures for the primary and baseline publications. The data from the trial will provide the first large-scale randomized evidence for the use of intensive anti-platelet therapy for preventing recurrence after acute stroke and transient ischemic attack.
Capital Deployment Roundtable: A Discussion of Corporate Investment and Payout Policy
Authors: Clancy Paul , Mauboussin Michael , Briscoe John , Ostfeld Scott , Hilal Paul , Milano Greg , McCormack John , Chew Don
Published: December 2014

U.S. companies are now reportedly earning record‐high operating returns on capital while at the same time continuing to set new records both for corporate cash holdings and distributions to investors in the form of dividends and stock repurchases. But are most of these companies really maximizing value? And what role, if any, do these large distributions play in creating value? These are the two main questions that are addressed by a small group that includes two senior corporate executives and two representatives of well‐known activist investors.

A number of panelists suggest that many companies, in misguided efforts to maximize returns on capital, have been using hurdle rates that are too high and so sacrificing value‐adding investment opportunities. As evidence for this claim, they cite evidence that, in recent years, the companies that have achieved the highest stock market returns appear to have made conscious decisions to reduce their returns on capital to pursue higher growth.

Another increasingly common charge against U.S. companies is their tendency to pay out excessive capital to investors, especially in the form of stock repurchases at prices that turn out to be too high. But this last practice, however widespread, may not be as troubling as it has been made out to be. Although it involves a wealth transfer from existing to selling shareholders, overall investor value is lost only if such buybacks lead to corporate underinvestment. But, as a number of panelists (including the activist investors) point out, such payouts of capital have generally functioned as a demonstration of corporate managers' commitment to investing and operating with the optimal, or value‐maximizing, level of capital—neither too much nor too little.
Bridging the Gap between Interest Rates and Investments
Authors: Zenner Marc , Junek Evan , Chivukula Ram
Published: December 2014

The links between interest rates, cost of capital, hurdle rates, and capital allocation have been remarkably weak during the last few years. For instance, whereas the current yield on the World Government Bond Index is a paltry 1.2%, survey evidence suggests that the median reported investment hurdle rate of S&P 100 companies is as high as 18%.

In this report, members of J.P Morgan's corporate finance advisory group explain why the cost of capital for most companies is unlikely to increase materially even if interest rates rise as projected. This suggests that companies have room to lower their hurdle rates. Moreover, as the authors argue, a reduction in hurdle rates is likely to be beneficial since excessively high hurdle rates can have the effect of reducing value by sacrificing profitable growth opportunities and increasing the firm's risk profile. The report concludes with a framework for corporate hurdle rates and capital allocation strategies designed to help companies make better investment decisions.
Selection on outlier loci and their association with adaptive phenotypes inLittorina saxatiliscontact zones
Authors: Hollander J. , Galindo J. , Butlin R. K.
Published: December 2014

A fundamental issue in speciation research is to evaluate phenotypic variation and the genomics driving the evolution of reproductive isolation between sister taxa. Above all, hybrid zones are excellent study systems for researchers to examine the association of genetic differentiation, phenotypic variation and the strength of selection. We investigated two contact zones in the marine gastropodLittorina saxatilisand utilized landmark‐based geometric morphometric analysis together with amplified fragment length polymorphism (AFLP) markers to assess phenotypic and genomic divergence between ecotypes under divergent selection. From genetic markers, we calculated the cline width, linkage disequilibrium and the average effective selection on a locus. Additionally, we conducted an association analysis linking the outlier loci and phenotypic variation between ecotypes and show that a proportion of outlier loci are associated with key adaptive phenotypic traits.
Lotus hosts delimit the mutualism–parasitism continuum of Bradyrhizobium
Authors: Regus J. U. , Gano K. A. , Hollowell A. C. , Sofish V. , Sachs J. L.
Published: December 2014

Symbioses are modelled as evolutionarily and ecologically variable with fitness outcomes for hosts shifting on a continuum from mutualism to parasitism. In a classic example, rhizobia fix atmospheric nitrogen for legume hosts in exchange for photosynthetic carbon. Rhizobial infection often enhances legume growth, but hosts also incur interaction costs because of root tissues and or metabolites needed to support symbionts in planta. Rhizobia exhibit genetic variation in symbiotic effectiveness, and ecological changes in light or mineral nitrogen availability can also alter the benefits of rhizobial infection for hosts. The net effects of symbiosis thus can range from mutualistic to parasitic in a context‐dependent manner. We tested the extent of the mutualism–parasitism continuum in the legume–rhizobium symbiosis and the degree to which host investment can shape its limits. We infected Lotus strigosus with sympatric Bradyrhizobium genotypes that vary in symbiotic effectiveness. Inoculations occurred under different mineral nitrogen and light regimes spanning ecologically relevant ranges. Net growth benefits of Bradyrhizobium infection varied for Lotus and were reduced or eliminated dependent on Bradyrhizobium genotype, mineral nitrogen and light availability. But we did not detect parasitism. Lotus proportionally reduced investment in Bradyrhizobium as net benefit from infection decreased. Lotus control occurred primarily after infection, via fine‐scale modulation of nodule growth, as opposed to control over initial nodulation. Our results show how divestment of symbiosis by Lotus can prevent shifts to parasitism.
Visual Impairment and Incident Mobility Limitations: The Health, Aging and Body Composition Study
Authors: Swenor Bonnielin K. , Simonsick Eleanor M. , Ferrucci Luigi , Newman Anne B. , Rubin Susan , Wilson Valerie ,   the Health, Aging and Body Composition Study
Published: December 2014

Objectives

To examine the association between multiple measures of visual impairment (VI) and incident mobility limitations in older adults.

Design

Prospective observational cohort study.

Setting

Memphis, Tennessee, and Pittsburgh, Pennsylvania.

Participants

Health, Aging and Body Composition study participants aged 70 to 79 without mobility limitations at the Year 3 visit (N = 1,862).

Measurements

Vision was measured at the Year 3 visit, and VI was defined as distance visual acuity (VA) worse than 20/40, contrast sensitivity (CS) less than 1.55 log Contrast, and stereoacuity (SA) greater than 85 arcsec. Incident persistent walking and stair climbing limitation was defined as two consecutive 6‐month reports of any difficulty walking one‐quarter of a mile or walking up 10 steps after 1, 3, and 5 years of follow‐up.

Results

At Year 3 (baseline for these analyses), 7.4% had impaired VA, 27.2% had impaired CS, and 29.2% had impaired SA. At all follow‐up times, the incidence of walking and stair climbing limitations was higher in participants with VA, CS, or SA impairment. After 5 years, impaired CS and SA were independently associated with greater risk of walking limitation (hazard ratio (HR)CS = 1.3, 95% confidence interval (CI) = 1.1–1.7; HRSA = 1.3, 95% CI = 1.1–1.6) and stair climbing limitation (HRCS = 1.4, 95% CI = 1.1–1.8; HRSA = 1.3, 95% CI=1.1–1.7). Having impaired CS and SA was associated with greater risk of mobility limitations (HRwalking limitations = 2.0, 95% CI = 1.6–2.5; HRstair limitation = 2.1, 95% CI = 1.6–2.8).

Conclusion

Multiple aspects of VI may contribute to mobility limitations in older adults. Addressing more than one component of vision may be needed to reduce the effect of vision impairment on functional decline.
Combinations of Hd2 and Hd4 genes determine rice adaptability to Heilongjiang Province, northern limit of China
Authors: Li Xiufeng , Liu Huazhao , Wang Maoqing , Liu Hualong , Tian Xiaojie , Zhou Wenjia , Lü Tianxiao , Wang Zhenyu , Chu Chengcai , Fang Jun , Bu Qingyun
Published: December 2014

Heading date is a key trait in rice domestication and adaption, and a number of quantitative trait loci (QTLs) have been identified. The rice (Oryza sativa L.) cultivars in the Heilongjiang Province, the northernmost region of China, have to flower extremely early to fulfill their life cycle. However, the critical genes or different gene combinations controlling early flowering in this region have not been determined. QTL and candidate gene analysis revealed that Hd2/Ghd7.1/OsPRR37 plays a major role in controlling rice distribution in Heilongjiang. Further association analysis with a collection of rice cultivars demonstrated that another three major QTL genes (Hd4/Ghd7, Hd5/DTH8/Ghd8, and Hd1) also participate in regulating heading date under natural long day (LD) conditions. Hd2/Ghd7.1/OsPRR37 and Hd4/Ghd7 are two major QTLs and function additively. With the northward rice cultivation, the Hd2/Ghd7.1/OsPRR37 and Hd4/Ghd7 haplotypes became non‐functional alleles. Hd1 might be non‐functional in most Heilongjiang rice varieties, implying that recessive hd1 were selected during local rice breeding. Non‐functional Hd5/DTH8/Ghd8 is very rare, but constitutes a potential target for breeding extremely early flowering cultivars. Our results indicated that diverse genetic combinations of Hd1, Hd2, Hd4, and Hd5 determined the different distribution of rice varieties in this northernmost province of China.
Genome‐wide identification, expression analysis of auxin‐responsive GH3 family genes in maize (Zea mays L.) under abiotic stresses
Authors: Feng Shangguo , Yue Runqing , Tao Sun , Yang Yanjun , Zhang Lei , Xu Mingfeng , Wang Huizhong , Shen Chenjia
Published: December 2014

Auxin is involved in different aspects of plant growth and development by regulating the expression of auxin‐responsive family genes. As one of the three major auxin‐responsive families, GH3 (Gretchen Hagen3) genes participate in auxin homeostasis by catalyzing auxin conjugation and bounding free indole‐3‐acetic acid (IAA) to amino acids. However, how GH3 genes function in responses to abiotic stresses and various hormones in maize is largely unknown. Here, the latest updated maize (Zea mays L.) reference genome sequence was used to characterize and analyze the ZmGH3 family genes from maize. The results showed that 13 ZmGH3 genes were mapped on five maize chromosomes (total 10 chromosomes). Highly diversified gene structures and tissue‐specific expression patterns suggested the possibility of function diversification for these genes in response to environmental stresses and hormone stimuli. The expression patterns of ZmGH3 genes are responsive to several abiotic stresses (salt, drought and cadmium) and major stress‐related hormones (abscisic acid, salicylic acid and jasmonic acid). Various environmental factors suppress auxin free IAA contents in maize roots suggesting that these abiotic stresses and hormones might alter GH3‐mediated auxin levels. The responsiveness of ZmGH3 genes to a wide range of abiotic stresses and stress‐related hormones suggested that ZmGH3s are involved in maize tolerance to environmental stresses.