bluuebunny/crossref_metadata_2025 huggingface dataset:
ALMACAL V: absorption-selected galaxies with evidence for excited ISMs
Authors: Klitsch A , Zwaan M A , Péroux C , Smail I , Oteo I , Popping G , Swinbank A M , Ivison R J , Biggs A D
Published: October 2018

Gas-rich galaxies are selected efficiently via quasar absorption lines. Recently, a new perspective on such absorption-selected systems has opened up by studying the molecular gas content of absorber host galaxies using ALMA CO emission line observations. Here, we present an analysis of multiple CO transitions ($L^{\prime }_{\rm CO} \sim 10^9$ K km s−1) in two z ∼ 0.5 galaxies associated with one Ly α absorber towards J0238+1636. The CO spectral line energy distributions (CO SLEDs) of these galaxies appear distinct from that of typical star-forming galaxies at similar redshifts and is comparable with that of luminous infrared galaxies or active galactic nucleus (AGN). Indeed, these galaxies are associated with optically identified AGN activity. We infer that the CO line ratios and the αCO conversion factor differ from the Galactic values. Our findings suggest that at least a fraction of absorption-selected systems shows interstellar medium conditions deviating from those of normal star-forming galaxies. For a robust molecular gas mass calculation, it is therefore important to construct the CO SLED. Absorption line selection identifies systems with widely distributed gas, which may preferentially select interacting galaxies, which in turn will have more excited CO SLEDs than isolated galaxies. Furthermore, we raise the question whether quasar absorbers preferentially trace galaxy overdensities.
Cosmological simulations of the circumgalactic medium with 1 kpc resolution: enhanced H i column densities
Authors: van de Voort Freeke , Springel Volker , Mandelker Nir , van den Bosch Frank C , Pakmor Rüdiger
Published: October 2018

The circumgalactic medium (CGM), i.e. the gaseous haloes around galaxies, is both the reservoir of gas that fuels galaxy growth and the repository of gas expelled by galactic winds. Most cosmological, hydrodynamical simulations focus their computational effort on the galaxies themselves and treat the CGM more coarsely, which means small-scale structure cannot be resolved. We get around this issue by running zoom-in simulations of a Milky Way-mass galaxy with standard mass refinement and additional uniform spatial refinement within the virial radius. This results in a detailed view of its gaseous halo at unprecedented (1 kpc) uniform resolution with only a moderate increase in computational time. The improved spatial resolution does not impact the central galaxy or the average density of the CGM. However, it drastically changes the radial profile of the neutral hydrogen column density, which is enhanced at galactocentric radii larger than 40 kpc. The covering fraction of Lyman-Limit Systems within 150 kpc is almost doubled. We therefore conclude that some of the observational properties of the CGM are strongly resolution dependent. Increasing the resolution in the CGM, without increasing the resolution of the galaxies, is a promising and computationally efficient method to push the boundaries of state-of-the-art simulations.
activPAL-measured sitting levels and patterns in 9–10 years old children from a UK city
Authors: Sherry Aron P , Pearson Natalie , Ridgers Nicola D , Barber Sally E , Bingham Daniel D , Nagy Liana C , Clemes Stacy A
Published: October 2018

Background

There is insufficient evidence of sitting time in UK children from validated objective measures. This study explored sitting patterns in primary school children from Bradford, UK, using the validated activPAL inclinometer.

Methods

Overall, 79 children (9.8 (SD 0.3) years old, 52% boys; 70% South Asian) wore activPALs for 7 days. Total sitting time, sitting time accumulated in different bout lengths, and the proportion of wear time spent in these variables were explored and compared across different periods of the week.

Results

Children spent 614 ± 112 (median ± IQR) min/day on school days and 690 ± 150 min/day on weekend days sitting. The proportion of time spent sitting was significantly higher on weekend days compared to school days (mean±SD: 74 ± 10% versus 68 ± 8%,P < 0.001), as was the proportion of time accumulated in >30 min sitting bouts (mean±CI: 28 ± 27–33% versus 20 ± 20–22%, P < 0.001). The proportion of time spent sitting after school was significantly higher than during school time (mean±SD: 70 ± 8.4% versus 63 ± 8.3%,P < 0.001), as was the proportion of time spent in prolonged (>30 min) sitting bouts (mean±CI: 19 ± 16–22% versus 11 ± 10–14%, P < 0.001).

Conclusions

Children spent large proportions of their waking day sitting, often accumulated in prolonged uninterrupted bouts and particularly after school and on weekends. Interventions to reduce sitting time in children are urgently needed.
Is Welfare a Magnet for Migration? Examining Universal Welfare Institutions and Migration Flows
Authors: Ponce Aaron
Published: October 2018

This study extends macro-structural research on international migration flows by going beyond conventional economic, demographic, and geographic explanations. Prior extensions suggest that migrants are drawn to places where welfare benefits are generous. I test the welfare magnet hypothesis while proposing an alternative explanation for migration: the prospect for inclusion. The analysis uses a comprehensive point-to-point migration dataset for a sample of robust welfare states, the universalist countries of Nordic Europe, and similarly positioned destinations representing other welfare types to examine destinations’ commitments to inclusion, humanitarianism, and welfare generosity. Results reveal no evidence for a magnet effect to the most generous welfare states in the world net of other recognized factors, and even suggest a negative influence linked to the region’s high cost of living. Migrants are instead drawn by the promise of social and political inclusion, migrating to destinations where co-ethnics have become full-fledged citizens. Additional evidence points to the role of international commitments to humanitarianism in augmenting flows. Findings integrate insights on contexts of immigrant reception with research on migration flows, thus contributing to a political sociology of immigration and citizenship and opening new avenues for research on the determinants of migration to newer, more distant locations.
Biological treatments for severe asthma: where do we stand?
Authors: Busse William W.
Published: October 2018

Purpose of review

For patients with severe asthma, disease control is not achieved resulting in persistent morbidity and risks for exacerbations. The advent of biologics is providing a new form of treatment for many with severe asthma.

Recent findings

Four mAb biologics are approved for clinical use: omalizumab (anti-IgE) and three antieosinophilic interventions (mepolizumab, reslizumab, and benralizumab). These four biologics target components of the type 2-inflammatory pathway which is reflected by biomarkers: peripheral blood eosinophils and exhaled nitric oxide. In severe asthma, biologics have reduced asthma exacerbations. The antieosinophilic biologics have also improved lung function. The safety profile of these biologics has been good.

For patients with severe asthma and biomarkers indicating a type 2 inflammatory pathway, the addition of biologics has proven to be an effective approach to achieve disease control and is an appropriate next step treatment.
The challenge of cardiomyopathies and heart failure in pregnancy
Authors: Limongelli Giuseppe , Rubino Marta , Esposito Augusto , Russo Mariagiovanna , Pacileo Giuseppe
Published: October 2018

Purpose of review

To discuss the risk preexisting or new onset cardiomyopathy/heart failure (CMP/heart failure) in pregnant woman, and recent insights regarding their management and therapy.

Recent findings

Recent data from the European Registry on Pregnancy and Heart disease of the European Society of Cardiology (ROPAC) suggest that, after an adequate prepregnancy evaluation in specialized centres, the vast majority of pregnancies are safe for both mother and foetus. A tailored approach is required according to cardiac phenotype (i.e. type of cardiomyopathy), clinical and functional status, and new potential treatments (i.e. bromocriptine in patients with peripartum cardiomyopathy).

In clinical practice, prepregnancy cardiac evaluation is mandatory, including evaluation of the clinical status, standard ECG (and 24–48 h monitoring, whenever required), and imaging, to define the individual risk profile. In presence of severe symptoms (advanced New York Heart Association class), cardiac dysfunction (moderate–severe reduced ejection fraction), haemodynamic load (left ventricular outflow tract obstruction, pulmonary hypertension), pregnancy is contraindicated. A tailored monitoring is warranted in other cases (mild–moderate risk pregnancies). Likewise, in women who develop PPCM, a risk stratification and tailored monitoring and therapy should be achieved by an expert, multidisciplinary team, including cardiologists, gynaecologists, obstetricians, genetic counsellor, and psychologists.
A Placebo-controlled Study of PF-06473871 (Anti-Connective Tissue Growth Factor Antisense Oligonucleotide) in Reducing Hypertrophic Skin Scarring
Authors: Gale Jeremy D. , Jensen Jeff , Berman Gabe , Freimuth William , Li Gang , Pleil Andreas , Kutty Malik , Rosenthal Andrew , Boswell C.B. , Noah V., E. Magnus , Young Leroy
Published: October 2018

Background:

Connective tissue growth factor (CTGF) is a matricellular protein that plays a key role in wound healing and scar formation. Inhibition of CTGF by a specific antisense oligonucleotide significantly reduced scarring and fibrosis in animal models. This study examined whether an antisense oligonucleotide that inhibits human CTGF expression could reduce the severity of hypertrophic scar formation in patients following surgical revision of preexisting breast scars.

Methods:

This study was a 24-week multicenter, randomized, double-blind, within-subject, placebo-controlled phase 2b study evaluating the efficacy and safety of PF-06473871 in 2 regimens of either 3 or 4 intradermal injections (postsurgery weeks 2, 5, 8, and 11) of 5 mg/cm adjacent to the new surgical incision. One hundred subjects with bilateral hypertrophic scars resulting from prior breast surgery were randomized. Efficacy was determined by the Patient and Observer Scar Assessment Scale (POSAS).

Results:

The Physician/Observer POSAS overall opinion score at (week 24) for the 4-injection regimen demonstrated a statistically significant (P = 0.022) treatment difference from placebo of 0.68, and the treatment difference for the 3-injection regimen was nonsignificant (P = 0.4). Physician evaluation of scar severity at (week 24) with the photo-guide in the 4-injection regimen had a significant reduction (point estimate of treatment difference of 0.43 favoring PF-06473871). The surgical effect was approximately 2.0 at week 24 and was nearly 3 times greater than the treatment effect. Patient evaluations using the POSAS and photo-guide were not significantly improved with either dose regimen. PF-06473871 was generally well tolerated systemically and locally.

Conclusion:

The 4-dose regimen of PF-06473871 provided statistically significant improvement, inhibiting severity of hypertrophic scar formation based on physician assessment. However, the effect of revision surgery alone is significant and may dominate the treatment effect of PF-06473871.
Is Self-Reported Knee Stability Associated With Symptoms, Function, and Quality of Life in People With Knee Osteoarthritis After Anterior Cruciate Ligament Reconstruction?
Authors: Hart Harvi F. , Collins Natalie J. , Ackland David C. , Crossley Kay M.
Published: October 2018

Objective:

This study aimed to investigate the association of self-reported knee stability with symptoms, function, and quality of life in individuals with knee osteoarthritis after anterior cruciate ligament reconstruction (ACLR).

Setting:

Cross-sectional.

Participants:

Twenty-eight individuals with knee osteoarthritis, 5 to 12 years after ACLR.

Main Outcome Measures:

Self-reported knee stability was assessed using visual analogue scales (VAS) during hop for distance (HD), side-to-side hop (SSH), and one-leg rise (OLR). Symptoms [Knee Injury and Osteoarthritis Outcome Score (KOOS) pain, Anterior Knee Pain Scale (AKPS), and International Knee Documentation Committee form], self-reported function (KOOS-sport/rec), performance-based function (hopping and OLR), and quality of life (KOOS-QOL) were assessed. K-means clustering categorized individuals into low (n = 8) and high self-reported knee stability (n = 20) groups based on participants' VAS scores during functional tasks.

Results:

The low self-reported knee stability group had worse knee symptoms than the high self-reported knee stability group [KOOS-pain: mean difference −17 (95% confidence interval, −28 to −5); AKPS: −10 (−20 to −1)], and worse self-reported function [KOOS-sport/rec: −33 (−48 to −18)] and performance-based function [HD: −28 (−53 to −3); SSH: −10 (−20 to −1), OLR: −18 (−32 to −50)].

Conclusion:

Low self-reported stability is associated with worse symptoms, and worse self-reported and performance-based function. Further research is required to determine the causation relation of self-reported knee stability to knee symptoms and function in individuals with knee osteoarthritis after ACLR.
Management of RVAD Thrombosis in Biventricular HVAD Supported Patients: Case Series
Authors: Silva Enciso Jorge , Tran Hao A. , Brambatti Michela , Braun Oscar Ö. , Pretorius Victor , Adler Eric D.
Published: October 2018

Patients with biventricular assist devices (BIVAD) are severely critically ill compared with patients who receive left ventricular assist device (LVAD) support alone and portend a significant risk for greater adverse events including pump thrombosis (PT). Current approaches to treat PT are limited to LVAD with variable outcomes depending on the management strategy implemented. Moreover the management of PT in patients with BIVAD support, specifically to the right ventricular assist device (RVAD), is unknown. We describe the first care series to date on the management of PT in patients with durable right ventricular assist device and their outcomes.
Optimal duration of antibiotic treatment in Gram-negative infections
Authors: De Waele Jan J. , Martin-Loeches Ignacio
Published: October 2018

Purpose of review

Whilst many guidelines recommend limiting the use of antibiotics because of the increase in antimicrobial resistance (AMR), this strategy becomes challenging when dealing with severe infections in critically ill patients. Moreover, some Gram-negative bacilli (GNB) can exhibit mechanisms of resistance that make the patient more vulnerable to recurrence of infections. We reviewed recent data on the optimal duration of antibiotic therapy in these patients.

Recent findings

Apart from having no additional clinical benefit at a certain point after initiation, antibiotics might have negative effects. Prolonged antibiotic exposure has been associated to development of AMR and represents a strong reason to avoid long courses of antibiotic therapy in GNB infections. Recent data suggest that also patients with severe infections, in whom source control is adequate, can be managed with short-course antibiotic therapy.

The optimal duration of antibiotic therapy depends on many factors, but overall, many infections in the critically ill can be treated with short-course antibiotic therapy (7 days or less). The integration of signs of resolution, biomarkers, clinical judgment, and microbiologic eradication might help to define this optimal duration in patients with life-threatening infections caused by GNB.
Perfusion of Porcine Kidneys With Macromolecular Heparin Reduces Early Ischemia Reperfusion Injury
Authors: Sedigh Amir , Nordling Sofia , Carlsson Fredrik , Larsson Erik , Norlin Bo , Lübenow Norbert , Lennmyr Fredrik , Tufveson Gunnar , Magnusson Peetra U. , Lorant Tomas
Published: October 2018

Background

Previously, we have been able to demonstrate the possibility of coating the inner surface of the renal arteries in porcine kidneys with a heparin conjugate during hypothermic machine perfusion (HMP). The purpose of this study was to assess the efficacy of this treatment in reducing early ischemia-reperfusion injury.

Method

Brain death was induced in male landrace pigs by stepwise volume expansion of an epidural balloon catheter until negative cerebral perfusion pressure (CPP) was obtained. Both kidneys (matched pairs; n = 6 + 6) were preserved for 20 hours by HMP during which 50 mg heparin conjugate was added to one of the HMP systems (treated group). A customized ex vivo normothermic oxygenated perfusion (NP) system with added exogenous creatinine was used to evaluate early kidney function. Blood, urine and histological samples were collected during the subsequent 3 hours of NP.

Results

Kidney weight was lower at the end of NP (P = 0.017) in the treated group compared with control kidneys. The rate of decline in creatinine level was faster (P = 0.024), total urinary volume was higher (P = 0.031), and the level of urine neutrophil gelatinase-associated lipocalin (NGAL) was lower (P = 0.031) in the treated group. Histologically, less tubular changes were seen (P = 0.046). During NP intrarenal resistance remained lower (P < 0.0001) in the treated group.

Conclusions

Perfusion of porcine kidneys with heparin conjugate during HMP reduces preservation injury and improves organ function shortly after reperfusion. No increased risk of bleeding was seen in this setup. This protective strategy may potentially improve the quality of transplanted kidneys in the clinical setting.
Spatio-temporal patterns of thermal anomalies and drought over tropical forests driven by recent extreme climatic anomalies
Authors: Jimenez Juan C. , Barichivich Jonathan , Mattar Cristian , Takahashi Ken , Santamaría-Artigas Andrés , Sobrino José A. , Malhi Yadvinder
Published: October 2018

The recent 2015–2016 El Niño (EN) event was considered as strong as the EN in 1997–1998. Given such magnitude, it was expected to result in extreme warming and moisture anomalies in tropical areas. Here we characterize the spatial patterns of temperature anomalies and drought over tropical forests, including tropical South America (Amazonia), Africa and Asia/Indonesia during the 2015–2016 EN event. These spatial patterns of warming and drought are compared with those observed in previous strong EN events (1982–1983 and 1997–1998) and other moderate to strong EN events (e.g. 2004–2005 and 2009–2010). The link between the spatial patterns of drought and sea surface temperature anomalies in the central and eastern Pacific is also explored. We show that indeed the EN2015–2016 led to unprecedented warming compared to the other EN events over Amazonia, Africa and Indonesia, as a consequence of the background global warming trend. Anomalous accumulated extreme drought area over Amazonia was found during EN2015–2016, but this value may be closer to extreme drought area extents in the other two EN events in 1982–1983 and 1997–1998. Over Africa, datasets disagree, and it is difficult to conclude which EN event led to the highest accumulated extreme drought area. Our results show that the highest values of accumulated drought area over Africa were obtained in 2015–2016 and 1997–1998, with a long-term drying trend not observed over the other tropical regions. Over Indonesia, all datasets suggest that EN 1982–1983 and EN 1997–1998 (or even the drought of 2005) led to a higher extreme drought area than EN2015–2016. Uncertainties in precipitation datasets hinder consistent estimates of drought severity over tropical regions, and improved reanalysis products and station records are required.

This article is part of a discussion meeting issue ‘The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications’.
A successful prediction of the record CO2rise associated with the 2015/2016 El Niño
Authors: Betts Richard A. , Jones Chris D. , Knight Jeff. R. , Keeling Ralph. F. , Kennedy John. J. , Wiltshire Andrew J. , Andrew Robbie M. , Aragão Luiz E. O. C.
Published: October 2018

In early 2016, we predicted that the annual rise in carbon dioxide concentration at Mauna Loa would be the largest on record. Our forecast used a statistical relationship between observed and forecast sea surface temperatures in the Niño 3.4 region and the annual CO2rise. Here, we provide a formal verification of that forecast. The observed rise of 3.4 ppm relative to 2015 was within the forecast range of 3.15 ± 0.53 ppm, so the prediction was successful. A global terrestrial biosphere model supports the expectation that the El Niño weakened the tropical land carbon sink. We estimate that the El Niño contributed approximately 25% to the record rise in CO2, with 75% due to anthropogenic emissions. The 2015/2016 CO2rise was greater than that following the previous large El Niño in 1997/1998, because anthropogenic emissions had increased. We had also correctly predicted that 2016 would be the first year with monthly mean CO2above 400 ppm all year round. We now estimate that atmospheric CO2at Mauna Loa would have remained above 400 ppm all year round in 2016 even if the El Niño had not occurred, contrary to our previous expectations based on a simple extrapolation of previous trends.

This article is part of a discussion meeting issue ‘The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications’.
History of El Niño impacts on the global carbon cycle 1957–2017: a quantification from atmospheric CO
2
data
Authors: Rödenbeck C. , Zaehle S. , Keeling R. , Heimann M.
Published: October 2018

Interannual variations in the large-scale net ecosystem exchange (NEE) of CO
2
between the terrestrial biosphere and the atmosphere were estimated for 1957–2017 from sustained measurements of atmospheric CO
2
mixing ratios. As the observations are sparse in the early decades, available records were combined into a ‘quasi-homogeneous’ dataset based on similarity in their signals, to minimize spurious variations from beginning or ending data records. During El Niño events, CO
2
is anomalously released from the tropical band, and a few months later also in the northern extratropical band. This behaviour can approximately be represented by a linear relationship of the NEE anomalies and local air temperature anomalies, with sensitivity coefficients depending on geographical location and season. The apparent climate sensitivity of global total NEE against variations in pan-tropically averaged annual air temperature slowly changed over time during the 1957–2017 period, first increasing (though less strongly than in previous studies) but then decreasing again. However, only part of this change can be attributed to actual changes in local physiological or ecosystem processes, the rest probably arising from shifts in the geographical area of dominating temperature variations.

This article is part of a discussion meeting issue ‘The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications’.
Modelling tropical forest responses to drought and El Niño with a stomatal optimization model based on xylem hydraulics
Authors: Eller Cleiton B. , Rowland Lucy , Oliveira Rafael S. , Bittencourt Paulo R. L. , Barros Fernanda V. , da Costa Antonio C. L. , Meir Patrick , Friend Andrew D. , Mencuccini Maurizio , Sitch Stephen , Cox Peter
Published: October 2018

The current generation of dynamic global vegetation models (DGVMs) lacks a mechanistic representation of vegetation responses to soil drought, impairing their ability to accurately predict Earth system responses to future climate scenarios and climatic anomalies, such as El Niño events. We propose a simple numerical approach to model plant responses to drought coupling stomatal optimality theory and plant hydraulics that can be used in dynamic global vegetation models (DGVMs). The model is validated against stand-scale forest transpiration (
E
) observations from a long-term soil drought experiment and used to predict the response of three Amazonian forest sites to climatic anomalies during the twentieth century. We show that our stomatal optimization model produces realistic stomatal responses to environmental conditions and can accurately simulate how tropical forest
E
responds to seasonal, and even long-term soil drought. Our model predicts a stronger cumulative effect of climatic anomalies in Amazon forest sites exposed to soil drought during El Niño years than can be captured by alternative empirical drought representation schemes. The contrasting responses between our model and empirical drought factors highlight the utility of hydraulically-based stomatal optimization models to represent vegetation responses to drought and climatic anomalies in DGVMs.

This article is part of a discussion meeting issue ‘The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications’.
ENSO effects on the transpiration of eastern Amazon trees
Authors: Brum Mauro , Gutiérrez López Jose , Asbjornsen Heidi , Licata Julian , Pypker Thomas , Sanchez Gilson , Oiveira Rafael S.
Published: October 2018

Tree transpiration is important in the recycling of precipitation in the Amazon and might be negatively affected by El Niño–Southern Oscillation (ENSO)–induced droughts. To investigate the relative importance of soil moisture deficits versus increasing atmospheric demand (VPD) and determine if these drivers exert different controls over tree transpiration during the wet season versus the dry season (DS), we conducted sap flow measurements in a primary lowland tropical forest in eastern Amazon during the most extreme ENSO-induced drought (2015/2016) recorded in the Amazon. We also assessed whether trees occupying different canopy strata contribute equally to the overall stand transpiration (
T
stand
). Canopy trees were the primary source of
T
stand
. However, subcanopy trees are still important as they transpired an amount similar to other biomes around the globe. Tree water use was higher during the DS, indicating that during extreme drought trees did not reduce transpiration in response to low soil moisture. Photosynthetically active radiation and VPD exerted an overriding effect on water use patterns relative to soil moisture during extreme drought, indicating that light and atmospheric constraints play a critical role in controlling ecosystem fluxes of water. Our study highlights the importance of canopy and subcanopy trees to the regional water balance and highlights the resilience to droughts that these trees show during an extreme ENSO event.

This article is part of a discussion meeting issue ‘The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications’.
Dry and hot: the hydraulic consequences of a climate change–type drought for Amazonian trees
Authors: Fontes Clarissa G. , Dawson Todd E. , Jardine Kolby , McDowell Nate , Gimenez Bruno O. , Anderegg Leander , Negrón-Juárez Robinson , Higuchi Niro , Fine Paul V. A. , Araújo Alessandro C. , Chambers Jeffrey Q.
Published: October 2018

How plants respond physiologically to leaf warming and low water availability may determine how they will perform under future climate change. In 2015–2016, an unprecedented drought occurred across Amazonia with record-breaking high temperatures and low soil moisture, offering a unique opportunity to evaluate the performances of Amazonian trees to a severe climatic event. We quantified the responses of leaf water potential, sap velocity, whole-tree hydraulic conductance (Kwt), turgor loss and xylem embolism, during and after the 2015–2016 El Niño for five canopy-tree species. Leaf/xylem safety margins (SMs), sap velocity andKwtshowed a sharp drop during warm periods. SMs were negatively correlated with vapour pressure deficit, but had no significant relationship with soil water storage. Based on our calculations of canopy stomatal and xylem resistances, the decrease in sap velocity andKwtwas due to a combination of xylem cavitation and stomatal closure. Our results suggest that warm droughts greatly amplify the degree of trees' physiological stress and can lead to mortality. Given the extreme nature of the 2015–2016 El Niño and that temperatures are predicted to increase, this work can serve as a case study of the possible impact climate warming can have on tropical trees.

This article is part of a discussion meeting issue ‘The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications’.
Actin dynamics drive microvillar motility and clustering during brush border assembly
Authors: Meenderink Leslie M , Tyska Matthew J.
Published: October 2018

During differentiation, transporting epithelial cells generate large arrays of microvilli known as a brush borders to enhance functional capacity. To develop our understanding of brush border formation, we used live cell imaging to visualize apical surface remodeling during early stages of this process. Strikingly, we found that individual microvilli exhibit persistent active motility, translocating across the cell surface at ~0.2 μm/min. Perturbation studies with inhibitors and photokinetic experiments revealed that microvillar motility is driven by actin assembly at the barbed-ends of core bundles, which in turn is linked to robust treadmilling of these structures. Because the apical surface of differentiating epithelial cells is crowded with nascent microvilli, persistent motility promotes collisions between protrusions and ultimately leads to their clustering and consolidation into higher order arrays. Thus, microvillar motility represents a previously unrecognized driving force for apical surface remodeling and maturation during epithelial differentiation.
The blind choreographer: evolution of social norms and correlated equilibria
Authors: Morsky Bryce , Akçay Erol
Published: October 2018

Social norms regulate and coordinate most aspects of human social life, yet they emerge and change as a result of individual behaviours, beliefs, and expectations. A satisfactory account for the evolutionary dynamics of social norms therefore has to link individual beliefs and expectations to population-level dynamics, where individual norms change according to their consequences for individuals. Here we present a new model of evolutionary dynamics of social norms that encompasses this objective and addresses the emergence of social norms. In this model, a norm is a set of behavioural prescriptions and a set of environmental descriptions that describe the expected behaviours of those with whom the norm holder will interact. These pre-scriptions and descriptions are functions of exogenous environmental events. These events have no intrinsic meaning or effect on the payoffs to individuals, yet beliefs/- superstitions regarding them can effectuate coordination. Though a norm's prescriptions and descriptions are dependent upon one another, we show how they emerge from random accumulations of beliefs. We categorize the space of social norms into several natural classes and study the evolutionary competition between these classes of norms. We apply our model to the Game of Chicken and the Nash Bargaining Game. Further, we show how the space of norms and evolutionary stability is dependent upon the correlation structure of the environment, and under which such correlation structures social dilemmas can be ameliorated or exacerbated.
Leveraging breeding values obtained from random regression models for genetic inference of longitudinal traits
Authors: Campbell Malachy T , Momen Mehdi , Walia Harkamal , Morota Gota
Published: October 2018

Understanding the genetic basis of dynamic plant phenotypes has largely been limited due to lack of space and labor resources needed to record dynamic traits, often destructively, for a large number of genotypes. However, the recent advent of image-based phenotyping platforms has provided the plant science community with an effective means to non-destructively evaluate morphological, developmental, and physiological processes at regular, frequent intervals for a large number of plants throughout development. The statistical frameworks typically used for genetic analyses (e.g. genome-wide association mapping, linkage mapping, and genomic prediction) in plant breeding and genetics are not particularly amenable for repeated measurements. Random regression (RR) models are routinely used in animal breeding for the genetic analysis of longitudinal traits, and provide a robust framework for modeling traits trajectories and performing genetic analysis simultaneously. We recently used a RR approach for genomic prediction of shoot growth trajectories in rice using 33,674 SNPs. In this study, we have extended this approach for genetic inference by leveraging genomic breeding values derived from RR models for rice shoot growth during early vegetative development. This approach provides improvements over a conventional single time point analyses for discovering loci associated with shoot growth trajectories. The RR approach uncovers persistent, as well as time-specific, transient quantitative trait loci. This methodology can be widely applied to understand the genetic architecture of other complex polygenic traits with repeated measurements.
Genomic Bayesian confirmatory factor analysis and Bayesian network to characterize a wide spectrum of rice phenotypes
Authors: Yu Haipeng , Campbell Malachy T. , Zhang Qi , Walia Harkamal , Morota Gota
Published: October 2018

With the advent of high-throughput phenotyping platforms, plant breeders have a means to assess many traits for large breeding populations. However, understanding the genetic interdependencies among high-dimensional traits in a statistically robust manner remains a major challenge. Since multiple phenotypes likely share mutual relationships, elucidating the interdependencies among economically important traits can better inform breeding decisions and accelerate the genetic improvement of plants. The objective of this study was to leverage confirmatory factor analysis and graphical modeling to elucidate the genetic interdependencies among a diverse agronomic traits in rice. We used a Bayesian network to depict conditional dependencies among phenotypes, which can not be obtained by standard multitrait analysis. We utilized Bayesian confirmatory factor analysis which hypothesized that 48 observed phenotypes resulted from six latent variables including grain morphology, morphology, flowering time, physiology, yield, and morphological salt response. This was followed by studying the genetics of each latent variable, which is also known as factor, using single nucleotide polymorphisms. Bayesian network structures involving the genomic component of six latent variables were established by fitting four algorithms (i.e., Hill Climbing, Tabu, Max-Min Hill Climbing, and General 2-Phase Restricted Maximization algorithms). Physiological components influenced the flowering time and grain morphology, and morphology and grain morphology influenced yield. In summary, we show the Bayesian network coupled with factor analysis can provide an effective approach to understand the interdependence patterns among phenotypes and to predict the potential influence of external interventions or selection related to target traits in the interrelated complex traits systems.
TIN2 functions with TPP1/POT1 to stimulate telomerase processivity
Authors: Pike Alexandra M. , Strong Margaret A. , Ouyang John Paul T. , Connelly Carla J. , Greider Carol W.
Published: October 2018

Telomere length maintenance is crucial for cells that divide many times. TIN2 is an important regulator of telomere length, and mutations in TINF2, the gene encoding TIN2, cause short telomere syndromes. While the genetics underscore the importance of TIN2, the mechanism through which TIN2 regulates telomere length remains unclear. Here, we characterize the effects of TIN2 on telomerase activity. We identified a new isoform in human cells, TIN2M, that is expressed at similar levels to previously studied TIN2 isoforms. Additionally, we found that all three TIN2 isoforms stimulated telomerase processivity beyond the previously characterized stimulation by TPP1/POT1. Mutations in the TPP1 TEL-patch abrogated this stimulation, implicating TIN2 as a component of the TPP1/POT1 processivity complex. All three TIN2 isoforms localized to telomeres in vivo but had distinct effects on telomere length, suggesting they are functionally distinct. These data contrast previous descriptions of TIN2 a simple scaffolding protein, showing that TIN2 isoforms directly regulate telomerase.
Human telomere repeat binding factor TRF1 replaces TRF2 bound to shelterin core hub TIN2 when TPP1 is absent
Authors: Janovič Tomáš , Stojaspal Martin , Veverka Pavel , Horáková Denisa , Hofr Ctirad
Published: October 2018

Human telomeric repeat binding factors TRF1, TRF2 along with TIN2 form a core of shelterin complex that protects chromosome ends against unwanted end-joining and DNA repair. We applied a single-molecule approach to assess TRF1-TIN2-TRF2 complex formation in solution at physiological conditions. Fluorescence Cross-Correlation Spectroscopy (FCCS) was used to describe the complex formation by analyzing how coincident fluctuations of differently labeled TRF1 and TRF2 correlate when they move together through the confocal volume of the microscope. We observed, at the single-molecule level, that TRF1 effectively substituted TRF2 on TIN2. We assessed the effect of another telomeric factor TPP1 that recruits telomerase to telomeres. We found that TPP1 upon binding to TIN2 induces allosteric changes that expand TIN2 binding capacity, such that TIN2 can accommodate both TRF1 and TRF2 simultaneously. We suggest a molecular model that explains why TPP1 is essential for the stable formation of TRF1-TIN2-TRF2 core complex.
Physical and functional interaction between SET1/COMPASS complex component CFP-1 and a Sin3 HDAC complex
Authors: Beurton F. , Stempor P. , Caron M. , Appert A. , Dong Y. , Chen R. , Cluet D. , Couté Y. , Herbette M. , Huang N. , Polveche H. , Spichty M. , Bedet C. , Ahringer J. , Palladino F.
Published: October 2018

The CFP1 CXXC zinc finger protein targets the SET1/COMPASS complex to non-methylated CpG rich promoters to implement tri-methylation of histone H3 Ly4 (H3K4me3). Although H3K4me3 is widely associated with gene expression, the effects of CFP1 loss depend on chromatin context, so it is important to understand the relationship between CFP1 and other chromatin factors. Using a proteomics approach, we identified an unexpected link betweenC. elegansCFP-1 and a Rpd3/Sin3 histone deacetylase complex. We find that mutants of CFP-1, SIN-3, and the catalytic subunit SET-2/SET1 have similar phenotypes and misregulate common genes. CFP-1 directly binds SIN-3 through a region including the conserved PAH1 domain and recruits SIN-3 and the HDA-1/HDAC subunit to H3K4me3 enriched promoters. Our results reveal a novel role for CFP-1 in mediating interaction between SET1/COMPASS and a Sin3 HDAC complex at promoters and uncover coordinate regulation of gene expression by chromatin complexes having distinct activities.
A complete chromosome substitution mapping panel reveals genome-wide epistasis in Arabidopsis
Authors: Wijnen Cris L. , Botet Ramon , van de Belt José , Deurhof Laurens , de Jong Hans , de Snoo C. Bastiaan , Dirks Rob , Boer Martin P. , van Eeuwijk Fred A. , Wijnker Erik , Keurentjes Joost J.B.
Published: October 2018

Chromosome substitution lines (CSLs) are tentatively supreme resources to investigate non-allelic genetic interactions. However, the difficulty of generating such lines in most species largely yielded imperfect CSL panels, prohibiting a systematic dissection of epistasis. Here, we present the development and use of a unique and complete panel of CSLs inArabidopsis thaliana, allowing the full factorial analysis of epistatic interactions. A first comparison of reciprocal single chromosome substitutions revealed a dependency of QTL detection on different genetic backgrounds. The subsequent analysis of the complete panel of CSLs enabled the mapping of the genetic interactors and identified multiple two- and three-way interactions for different traits. Some of the detected epistatic effects were as large as any observed main effect, illustrating the impact of epistasis on quantitative trait variation. We, therefore, have demonstrated the high power of detection and mapping of genome-wide epistasis, confirming the assumed supremacy of comprehensive CSL sets.

One sentence summary

Development of a complete panel of chromosome substitution lines enables high power mapping of epistatic interactions inArabidopsis thaliana.
Composition is the core driver of the language-selective network
Authors: Mollica Francis , Diachek Evgeniia , Mineroff Zachary , Kean Hope , Siegelman Matthew , Piantadosi Steven T. , Futrell Richard , Qian Peng , Fedorenko Evelina
Published: October 2018

The fronto-temporal language network responds robustly and selectively to sentences. But the features of linguistic input that drive this response and the computations these language areas support remain debated. Two key features of sentences are typically confounded in natural linguistic input: words in sentences a) are semantically and syntactically combinable into phrase- and clause-level meanings, and b) occur in an order licensed by the language’s grammar. Inspired by recent psycholinguistic work establishing that language processing is robust to word order violations, we hypothesized that the core linguistic computation is composition, and, thus, can take place even when the word order violates the grammatical constraints of the language. This hypothesis predicts that a linguistic string should elicit a sentence-level response in the language network as long as the words in that string can enter into dependency relationships as in typical sentences. We tested this prediction across two fMRI experiments (total N=47) by introducing a varying number of local word swaps into naturalistic sentences, leading to progressively less syntactically well-formed strings. Critically, local dependency relationships were preserved because combinable words remained close to each other. As predicted, word order degradation did not decrease the magnitude of the BOLD response in the language network, except when combinable words were so far apart that composition among nearby words was highly unlikely. This finding demonstrates that composition is robust to word order violations, and that the language regions respond as strongly as they do to naturalistic linguistic input as long as composition can take place.
Characterization of the gastric motility response to human motilin and erythromycin in human motilin receptor-expressing transgenic mice
Authors: Kato Shinichi , Takahashi Aoi , Shindo Mai , Yoshida Ayano , Kawamura Tomoe , Matsumoto Kenjiro , Matsuura Bunzo
Published: October 2018

Motilin is a gastrointestinal peptide hormone that stimulates gastrointestinal motility. Motilin is produced primarily in the duodenum and jejunum. Motilin receptors (MTLRs) are G protein-coupled receptors that may represent a clinically useful pharmacological target as they can be activated by erythromycin. The functions of motilin are highly species-dependent and remain poorly understood. As a functional motilin system is absent in rodents such as rats and mice, these species are not commonly used for basic studies. In this study, we examine the usefulness of human MTLR-overexpressing transgenic (hMTLR-Tg) mice by identifying the mechanisms of the gastric motor response to human motilin and erythromycin.

The distribution of hMTLR was examined immunohistochemically in male wild-type (WT) and hMTLR-Tg mice. The contractile response of gastric strips was measured isometrically in an organ bath, while gastric emptying was determined using phenol red.

hMTLR expression was abundant in the gastric smooth muscle layer but more potently expressed in the myenteric plexus of hMTLR-Tg mice but not WT mice. hMTLR was not co-localized with vesicular acetylcholine transporter, a marker of cholinergic neurons in the myenteric plexus. Treatment with human motilin and erythromycin caused concentration-dependent contraction of gastric strips obtained from hMTLR-Tg mice but not from WT mice.

The contractile response to human motilin and erythromycin in hMTLR-Tg mice was affected by neither atropine nor tetrodotoxin and was totally absent in Ca2+-free conditions. Furthermore, intraperitoneal injection of erythromycin significantly promoted gastric emptying in hMTLR-Tg mice but not in WT mice.

Human motilin and erythromycin stimulate the gastric motor response in hMTLR-Tg mice. This action is mediated by direct contraction of smooth muscle via the influx of extracellular Ca2+. Thus, hMTLR-Tg mice may be useful for the evaluation of MTLR agonists as gastric prokinetic agents.
Sufficient therapeutic effect of cryopreserved frozen adipose-derived regenerative cells on burn wounds
Authors: Kaita Yasuhiko , Tarui Takehiko , Yoshino Hideaki , Matsuda Takeaki , Yamaguchi Yoshihiro , Nakagawa Takatoshi , Asahi Michio , Ii Masaaki
Published: October 2018

The purpose of this study was to evaluate whether cryopreserved (frozen) adipose-derived regenerative cells (ADRCs) have a therapeutic effect on burn wound healing as well as freshly isolated (fresh) ADRCs.

Full thickness burns were created on dorsum of nude mice and burn wound was excised. The wound was covered by artificial dermis with; (i) fresh ADRCs, (ii) frozen ADRCs, and (iii) PBS (control). The assessment for wound healing was performed by morphological, histopathological and immunohistochemical analyses.

In vivo analyses exhibited the significant therapeutic effect of frozen ADRCs on burn wound healing up to the similar or higher level of fresh ADRCs. There were significant differences of wound closure, epithelized tissue thickness, and neovascularization between the treatment groups and control group. Although there was no significant difference of therapeutic efficacy between fresh ADRC group and frozen ADRC group, frozen ADRCs improved burn wound healing process in dermal regeneration with increased great type I collagen synthesis compared with fresh ADRCs.

These findings indicate that frozen ADRCs allow us to apply not only quickly but also for multiple times, and the cryopreserved ADRCs could therefore be useful for the treatment of burn wounds in clinical settings.