bluuebunny/crossref_metadata_2025 huggingface dataset:
Using genetic instruments to estimate interactions in Mendelian Randomization studies
Authors: North Teri-Louise , Davies Neil M , Harrison Sean , Carter Alice R , Hemani Gibran , Sanderson Eleanor , Tilling Kate , Howe Laura D
Published: February 2019

BACKGROUND

The interactive effect of two exposures on an outcome can be confounded. We demonstrate the use of Mendelian Randomization (MR) to estimate unconfounded additive interactions.

METHODS

Using simulation, we test an extension to multivariable MR using two-stage least squares to estimate the additive interaction between two continuous exposures on a continuous outcome, including scenarios where one exposure has a causal effect on the other (mediation). The interaction parameters were set to be one third of the main effect’s parameters to impose a limit on the variance explained by interaction terms. We compare the performance of the two-stage least squares estimator to a Factorial MR design, in which genetic risk scores for each exposure are dichotomised to create four groups, akin to a factorial randomized controlled trial. As an illustrative example, we apply factorial MR and the 2SLS estimator to the interactive effect of education and BMI on systolic blood pressure in UK Biobank.

RESULTS

Our simulations demonstrate that factorial MR has very low statistical power; 5-7% at N=50,000 and 8-23% at N=500,000 across the range of parameters tested. The two-stage least squares estimator had higher power to detect interactions than factorial MR and a lower type I error. For N=500,000, the two-stage least squares estimator had a power ranging from 29.7-92.9% and a type I error ranging from 4-6%. 95% Monte Carlo confidence intervals suggested that the estimator was unbiased to a reasonable degree of accuracy at this sample size. In comparison, the power at N=50,000 was 7-55%.

CONCLUSIONS

A two-stage least squares estimator using genetic risk scores for each exposure is a more powerful alternative for detecting an unconfounded additive interaction of two exposures on an outcome than existing approaches that rely on dichotomising genetic risk scores, but it requires a large sample size and instruments of adequate strength.
Adhesive defence mucus secretions in the red triangle slug (Triboniophorus graeffei) can incapacitate adult frogs
Authors: Gould John , Valdez Jose W. , Upton Rose
Published: February 2019

Gastropods are known to secrete mucus for a variety of purposes, including locomotion, reproduction, adhesion to surfaces, and lubrication. A less commonly known function of mucus secretion in this group involves its use as a defence against predation. Among the terrestrial slugs, mucus that serves this particular purpose has been studied for only a handful of species under laboratory conditions, where it is thought to be produced for self-fouling or to make individuals difficult to consume. However, the mechanisms of how these defensive secretions operate and their effectiveness in deterring predation in the natural world have not be described in much detail. In this study, we provide evidence of adhesive mucus secretions in the red triangle slug (Triboniophorus graeffei) as an adaptation against predation. Field observations of a large red-eyed green tree frog (Litoria chloris) trapped in the mucus secretions of a nearbyT. graeffeirevealed that this mucus serves to incapacitate predators rather than just simply as an overall deterrence. Mechanical stimulation ofT. graeffeiunder laboratory conditions revealed that adhesive secretions were produced from discrete sections of the dorsal surface when disturbed, leading to the production of a highly sticky and elastic mucus that was unlike the thin and slippery mucus used during locomotion. The adhesiveness of the defensive secretions was strengthened and reactivated when in contact with water. This appears to not only be the first description of defensive mucus production in this slug species but one of the first natural observations of the use of adhesive defence secretions to incapacitate a predator. The biomechanical properties of this mucus and its ability to maintain and strengthen its hold under wet conditions make it potentially useful in the development of new adhesive materials.
Microclimate predicts frost-hardiness of alpineArabidopsis thalianapopulations better than altitude because the microclimate effect increases with altitude
Authors: Lampei Christian , Wunder Jörg , Wilhalm Thomas , Schmid Karl J.
Published: February 2019

In mountain regions average temperatures decrease at higher altitudes. In addition, microenvironmental conditions can strongly affect microclimate and may counteract average effects of altitude.

We investigated winter frost hardiness ofArabidopsis thalianaaccessions originating from 13 sites along altitudinal gradients in the Southern Alps during three winters on an experimental field station on the Swabian Jura and compared levels of frost damage with the observed number of frost days (<1°C) in eight collection sites.

We found that frost-hardiness increased with altitude in a log-linear fashion. This is consistent with adaptation to higher frequency of frost conditions, but also indicates a decreasing rate of change in frost hardiness with increasing altitude. Moreover, the number of frost days measured with temperature loggers at the original collection sites correlated much better with frost-hardiness than the altitude of collection sites, suggesting that populations were adapted to their local microclimate. Notably, the variance in frost days across sites increased exponentially with altitude.

Together, our results suggest that strong microclimate heterogeneity of high alpine environments may preserve functional genetic diversity in small populations. This challenges the suitability of habitat predictions based on large scale climatic variables (or proxies, such as altitude) for topographically complex areas.
Object Detection Networks and Augmented Reality for Cellular Detection in Fluorescence Microscopy Acquisition and Analysis
Authors: Waithe D , Brown JM , Reglinski K , Diez-Sevilla I , Roberts D , Eggeling Christian
Published: February 2019

In this paper we demonstrate the application of object detection networks for the classification and localization of cells in fluorescence microscopy. We benchmark two leading object detection algorithms across multiple challenging 2-D microscopy datasets as well as develop and demonstrate an algorithm which can localize and image cells in 3-D, in real-time. Furthermore, we exploit the fast processing of these algorithms and develop a simple and effective Augmented Reality (AR) system for fluorescence microscopy systems. Object detection networks are well-known high performance networks famously applied to the task of identifying and localizing objects in photography images. Here we show their application and efficiency for localizing cells in fluorescence microscopy images. Object detection algorithms are typically trained on many thousands of images, which can be prohibitive within the biological sciences due to the cost of imaging and annotating large amounts of data. Through taking different cell types and assays as an example, we show that with some careful considerations it is possible to achieve very high performance with datasets with as few as 26 images present. Using our approach, it is possible for relatively non-skilled users to automate detection of cell classes with a variety of appearances and enable new avenues for automation of conventionally manual fluorescence microscopy acquisition pipelines.
Evaluation of Enhanced Learning Techniques for Segmenting Ischaemic Stroke Lesions in Brain Magnetic Resonance Perfusion Images using a Convolutional Neural Network Scheme
Authors: Malla Carlos Uziel Perez , Valdes Hernandez Maria del C. , Rachmadi Muhammad Febrian , Komura Taku
Published: February 2019

Magnetic resonance (MR) perfusion imaging non-invasively measures cerebral perfusion, which describes the blood’s passage through the brain’s vascular network. Therefore it is widely used to assess cerebral ischaemia. Convolutional Neural Networks (CNN) constitute the state-of-the-art method in automatic pattern recognition and hence, in segmentation tasks. But none of the CNN architectures developed to date have achieved high accuracy when segmenting ischaemic stroke lesions, being the main reasons their heterogeneity in location, shape, size, image intensity and texture, especially in this imaging modality. We use a freely available CNN framework, developed for MR imaging lesion segmentation, as core algorithm to evaluate the impact of enhanced machine learning techniques, namely data augmentation, transfer learning and post-processing, in the segmentation of stroke lesions using the ISLES 2017 dataset, which contains expert annotated diffusion-weighted perfusion and diffusion brain MRI of 43 stroke patients. Of all the techniques evaluated, data augmentation with binary closing achieved the best results, improving the mean Dice score in 17% over the baseline model. Consistent with previous works, better performance was obtained in the presence of large lesions.
A global to local genomics analysis ofClostridioides difficileST1/RT027 identifies cryptic transmission events in a northern Arizona healthcare network
Authors: Williamson Charles H.D. , Stone Nathan E. , Nunnally Amalee E. , Hornstra Heidie M. , Wagner David M. , Roe Chandler C. , Vazquez Adam J. , Nandurkar Nivedita , Vinocur Jacob , Terriquez Joel , Gillece John , Travis Jason , Lemmer Darrin , Keim Paul , Sahl Jason W.
Published: February 2019

Clostridioides difficileis a ubiquitous, diarrheagenic pathogen often associated with healthcare-acquired infections that can cause a range of symptoms from mild, self-limiting disease to toxic megacolon and death. Since the early 2000s, a large proportion ofC. difficilecases have been attributed to the ribotype 027 (RT027) lineage, which is associated with sequence type 1 (ST1) in theC. difficilemultilocus sequence typing (MLST) scheme. The spread of ST1 has been attributed, in part, to resistance to fluoroquinolones used to treat un-related infections, which creates conditions ideal forC. difficilecolonization and proliferation. In this study, we analyzed 27 isolates from a healthcare network in northern Arizona, USA, and 1,352 public ST1 genomes to place locally-sampled isolates into a global context. Core genome, single nucleotide polymorphism (SNP) analysis demonstrated that at least 6 separate introductions of ST1 were observed in healthcare facilities in northern Arizona over an 18-month sampling period. A reconstruction of transmission networks identified potential nosocomial transmission of isolates following two of these introductions, which were only identified via whole genome sequence analysis. Antibiotic resistance heterogeneity was observed among ST1 genomes, including variability in resistance profiles among locally sampled ST1 isolates. To investigate why ST1 genomes are so common globally, we compared all high-qualityC. difficilegenomes and identified that ST1 genomes have gained and lost a number of genomic regions compared to all otherC. difficilegenomes; analyses of other toxigenicC. difficilesequence types demonstrates that this loss may be anomalous and could be related to niche specialization. These results suggest that a combination of antimicrobial resistance and gain and loss of specific genes may explain the prominent association of this sequence type withC. difficileinfection cases worldwide. The degree of genetic variability in ST1 suggests that classifying all ST1 genomes into a quinolone-resistant hypervirulent clone category may not be appropriate. Whole genome sequencing of clinicalC. difficileisolates provides a high-resolution surveillance strategy for monitoring persistence and transmission ofC. difficileand for assessing the performance of infection prevention and control strategies.
Oscillating-flow Thermal Gradient PCR
Authors: Kopparthy Varun L. , Crews Niel D.
Published: February 2019

We report the development of a versatile system based on oscillating-flow methodology in a thermal gradient system for nucleic acid analysis. Analysis of DNA and RNA samples were performed in the device, without additional temperature control and complexity. The technique reported in this study eliminates the need for predetermined fluidic channels for thermocycles, and complexity involved with additional incubation steps required for RNA amplification. A microfluidic device was fabricated using rapid prototyping by simply sandwiching dual side adhesive Kapton tape and a PDMS spacer between glass microscope slides. Amplification of the 181-bp segment of a viral phage DNA (ΦX174) and B2M gene in human RNA samples was demonstrated using the system. The developed system enables simultaneous acquisition of amplification and melt curves, eliminating the need for post-processing.
Updated MS2PIP web server delivers fast and accurate MS2 peak intensity prediction for multiple fragmentation methods, instruments and labeling techniques
Authors: Gabriels Ralf , Martens Lennart , Degroeve Sven
Published: February 2019

MS2PIP is a data-driven tool that accurately predicts peak intensities for a given peptide’s fragmentation mass spectrum. Since the release of the MS2PIP web server in 2015, we have brought significant updates to both the tool and the web server. Next to the original models for CID and HCD fragmentation, we have added specific models for the TripleTOF 5600+ mass spectrometer, for TMT-labeled peptides, for iTRAQ-labeled peptides and for iTRAQ-labeled phosphopeptides. Because the fragmentation pattern is heavily altered in each of these cases, these additional models greatly improve the prediction accuracy for their corresponding data types. We have also substantially reduced the computational resources required to run MS2PIP, and have completely rebuilt the web server, which now allows predictions of up to 100.000 peptide sequences in a single request. The MS2PIP web server is freely available at https://iomics.ugent.be/ms2pip/.
Computational Insights Into Avidity of Polymeric Multivalent Binders
Authors: Zumbro E , Witten J , Alexander-Katz A
Published: February 2019

Multivalent binding interactions are commonly found throughout biology to enhance weak monovalent binding such as between glycoligands and protein receptors. Designing multivalent polymers to bind to viruses and toxic proteins is a promising avenue for inhibiting their attachment and subsequent infection of cells. Several studies have focused on oligomeric multivalent inhibitors and how changing parameters such as ligand shape and size, and linker length and flexibility affect binding. However, experimental studies of how larger structural parameters of multivalent polymers such as degree of polymerization affect binding avidity to targets have mixed results with some finding an improvement with longer polymers and some finding no effect. Here, we use Brownian dynamics simulations to provide a theoretical understanding of how degree of polymerization affects the binding avidity of multivalent polymers. We show that longer polymers increase binding avidity to multivalent targets, but reach a limit in binding avidity at high degrees of polymerization. We also show that when interacting with multiple targets simultaneously, longer polymers are able to use inter-target interactions to promote clustering and improve binding efficiency. We expect our results to narrow the design space for optimizing the structure and effectiveness of multivalent inhibitors, as well as be useful to understand biological design strategies for multivalent binding.
Development of a fixed list of descriptors for the qualitative behavioural assessment of shelter dogs
Authors: Arena Laura , Wemelsfelder Françoise , Messori Stefano , Ferri Nicola , Barnard Shanis
Published: February 2019

The shelter environment may have a severe impact on the quality of life of dogs, and there is thus a need to develop valid tools to assess their welfare. These tools should be sensitive not only to the animals’ physical health but also to their mental health, including the assessment of positive and negative emotions. Qualitative Behaviour Assessment (QBA) is an integrative ‘whole animal’ measure that captures the expressive quality of an animal’s demeanour, using descriptors such as ‘relaxed’, ‘anxious’, and ‘playful’. In this study, for the first time, we developed and tested a fixed-list of qualitative QBA descriptors for application to dogs living in kennels. A list of 20 QBA descriptors was developed based on literature search and an expert opinion survey. Inter-observer reliability was investigated by asking 11 observers to use these descriptors to score 13 video clips of kennelled dogs. Principal Component Analysis (PCA) was used to extract four main dimensions together explaining 70.9% of the total variation between clips. PC1 characterised curious/playful/excitable, sociable demeanour, PC2 ranged from comfortable/relaxed to anxious/nervous/stressed expression, PC3 described fearful demeanour, and PC4 characterized bored/depressed demeanour. Observers’ agreement on the ranking of video clips on these four expressive dimensions was good (Kendall’s W: 0.60-0.80). ANOVA showed a significant effect of observer on mean clip score on all PCs (p<0.05) due to a few observers scoring differently from the rest of the group. These results indicate the potential of the proposed list of QBA terms for sheltered dogs to serve as a non-invasive, easy-to-use assessment tool. However, the observers’ effect on mean scores points towards the need for adequate observer training. The QBA scoring tool can be integrated with existing welfare assessment protocols for shelter dogs and strengthen the power of those protocols to assess and evaluate the animals’ experience in shelters.
Unscrambling Fluorophore Blinking for Comprehensive Cluster Detection via Photoactivated Localization Microscopy
Authors: Platzer Rene , Rossboth Benedikt K. , Schneider Magdalena C. , Sevcsik Eva , Baumgart Florian , Stockinger Hannes , Schütz Gerhard J. , Huppa Johannes B. , Brameshuber Mario
Published: February 2019

Determining nanoscale protein distribution via Photoactivated Localization Microscopy (PALM) mandates precise knowledge of the applied fluorophore’s blinking properties to counteract overcounting artifacts that distort the resulting biomolecular distributions. Here, we present a readily applicable methodology to determine, optimize and quantitatively account for the blinking behavior of any PALM-compatible fluorophore. Using a custom-designed platform we revealed complex blinking of two photoswitchable fluorescence proteins (PS-CFP2 and mEOS3.2) and two photoactivatable organic fluorophores (PA Janelia Fluor 549 and Abberior CAGE 635) with blinking cycles on time scales of several seconds. Incorporating such detailed information in our simulation-based analysis package allowed for robust evaluation of molecular clustering based on individually recorded single molecule localization maps.

GRAPHICAL ABSTRACT
Microtubules form by progressively faster tubulin accretion, not by nucleation-elongation
Authors: Rice Luke M. , Moritz Michelle , Agard David A.
Published: February 2019

Microtubules are dynamic polymers that play fundamental roles in all eukaryotes. Despite their importance, how new microtubules form is poorly understood. Textbooks have focused on variations of a nucleation-elongation mechanism in which monomers rapidly equilibrate with an unstable oligomer (nucleus) that limits the rate of polymer formation; once formed, the polymer then elongates efficiently from this nucleus by monomer addition. Such models faithfully describe actin assembly, but they fail to account for how more complex polymers like hollow microtubules assemble. Here we articulate a new model for microtubule formation that has three key features: i) microtubules initiate via rectangular, sheet-like structures which grow faster the larger they become; ii) the dominant pathway proceeds via accretion, stepwise addition of longitudinal or lateral layers; iii) a ‘straightening penalty’ to account for the energetic cost of tubulin’s curved-to-straight conformational transition. This model can quantitatively fit experimental assembly data, providing new insights into biochemical determinants and assembly pathways for microtubule nucleation.
A Type III-A CRISPR-Cas system employs degradosome nucleases to ensure robust immunity
Authors: Chou-Zheng Lucy , Hatoum-Aslan Asma
Published: February 2019

CRISPR-Cas systems provide sequence-specific immunity against phages and mobile genetic elements using CRISPR-associated nucleases guided by short CRISPR RNAs (crRNAs). Type III systems exhibit a robust immune response that can lead to the extinction of a phage population, a feat coordinated by a multi-subunit effector complex that destroys invading DNA and RNA. Here, we demonstrate that a model Type III system in Staphylococcus epidermidis relies upon the activities of two degradosome-associated nucleases, PNPase and RNase J2, to mount a successful defense. Genetic, molecular, and biochemical analyses reveal that PNPase promotes crRNA maturation, and both nucleases are required for efficient clearance of phage-derived nucleic acids. Furthermore, functional assays show that RNase J2 is essential for immunity against diverse mobile genetic elements originating from plasmid and phage. Altogether, our observations reveal the evolution of a critical collaboration between two nucleic acid degrading machines which ensures cell survival when faced with phage attack.
Symmetry transitions during gating of the TRPV2 ion channel in lipid membranes
Authors: Zubcevic Lejla , Hsu Allen L. , Borgnia Mario J. , Lee Seok-Yong
Published: February 2019

The Transient Receptor Potential Vanilloid 2 (TRPV2) channel is a member of the temperature-sensing thermoTRPV family. Recent advances in cryo-electronmicroscopy (cryo-EM) and X-ray crystallography have provided many important insights into the gating mechanisms of thermoTRPV channels. Interestingly, crystallographic studies of ligand-dependent TRPV2 gating have shown that the TRPV2 channel adopts two-fold symmetric arrangements during the gating cycle. However, it was unclear if crystal packing forces played a role in stabilizing the two-fold symmetric arrangement of the channel. Here we employ cryo-EM to elucidate the structure of full-length rabbit TRPV2 in complex with the agonist resiniferatoxin (RTx) in nanodiscs and amphipol. We show that RTx induces two-fold symmetric conformations of TRPV2 in both environments. However, the two-fold symmetry is more pronounced in the native-like lipid environment of the nanodiscs. Our data offers insights into a gating pathway in TRPV2 involving symmetry transitions.
Opportunities for improved surveillance and control of infectious diseases from age-specific case data
Authors: Rodríguez-Barraquer Isabel , Salje Henrik , Cummings Derek AT
Published: February 2019

One of the challenges faced by global disease surveillance efforts is the lack of comparability across systems. Reporting commonly focuses on overall incidence, despite differences in surveillance quality between and within countries. For most immunizing infections, the age-distribution of incident cases provides a more robust picture of trends in transmission. We present a framework to estimate transmission intensity for dengue virus from age-specific incidence data, and apply it to 363 administrative units in Thailand, Colombia, Brazil and Mexico. Our estimates correlate well with those derived from seroprevalence data (the gold-standard), capture the expected spatial heterogeneity in risk, and correlate with known environmental drivers of transmission. We show how this approach could be used to guide the implementation of control strategies such as vaccination. Since age-specific counts are routinely collected by many surveillance systems, they represent a unique opportunity to further our understanding of disease burden and risk for many diseases.
Metabolic Energy Sensing by Mammalian CLC Anion/Proton Exchangers
Authors: Grieschat Matthias , Langschwager Katharina , Guzman Raul E. , Fahlke Christoph , Alekov Alexi K.
Published: February 2019

Mammalian CLC anion/proton exchangers control the pH and [Cl-] of the endolysosomal system, one of the major cellular nutrient uptake pathways. We explored the regulation of the vesicular transporters ClC-3, ClC-4, and ClC-5 by the adenylic system components ATP, ADP, and AMP. Using heterologous expression and whole-cell electrophysiology, we demonstrated that cytosolic ATP and ADP but not AMP and Mg2+-free ADP enhance CLC ion transport via binding to the protein C-terminal CBS domains. Biophysical investigations revealed that the effects depend on the delivery of intracellular protons into the CLC transport machinery and result from modified voltage-dependence and altered probability that CLC proteins undergo silent non-transporting cycles. Our findings demonstrate that the CLC CBS domains are able to serve as energy sensors by detecting changes in the cytosolic ATP/ADP/AMP equilibrium. The adenine nucleotide regulation of vesicular Cl-/H+ exchange creates a link between the activity of the endolysosomal system and the cellular metabolic state.
Autologous micrograft accelerates endogenous wound healing response through ERK-induced cell migration
Authors: Balli Martina , Vitali Francesca , Janiszewski Adrian , Caluwé Ellen , Cortés-Calabuig Alvaro , Duelen Robin , Ronzoni Flavio , Bellazzi Riccardo , Luttun Aernout , Cusella De Angelis Maria G. , Ceccarelli Gabriele , Lluis Frederic , Sampaolesi Maurilio
Published: February 2019

Defective fibroblast migration causes delayed wound healing (WH) and chronic skin lesions. Autologous micrograft (AMG) therapies have recently emerged as a new effective treatment able to improve wound healing capacity. However, the molecular mechanisms connecting their beneficial outcomes with the wound healing process are still unrevealed. Here, we show that AMG modulates primary fibroblast migration and accelerates skin re-epithelialization without affecting cell proliferation. We demonstrate that AMG is enriched in a pool of WH-associated growth factors that may provide the initiation signal for a faster endogenous wound healing response. This, in turn leads to increased cell migration rate by elevating activity of extracellular signal-regulated kinase (ERK) pathway and subsequent activation of matrix metalloproteinase expression and their extracellular enzymatic activity. Moreover, AMG-treated wounds showed increased granulation tissue formation and organized collagen content. Overall, we shed light on AMG molecular mechanism supporting its potential to trigger a highly improved wound healing process.
Decreased Activity of theGhrhrandGhPromoters Causes Dominantly Inherited GH Deficiency
Authors: Ariyasu Daisuke , Kubo Emika , Higa Daisuke , Shibata Shinsuke , Takaoka Yutaka , Sugimoto Michihiko , Imaizumi Kazunori , Hasegawa Tomonobu , Araki Kimi
Published: February 2019

Isolated growth hormone deficiency type II (IGHD2) is mainly caused by heterozygous splice-site mutations in intron 3 of theGH1gene. A dominant negative effect of the mutant growth hormone (GH) lacking exon 3 on wild-type GH secretion has been proposed; however, the molecular mechanisms involved are elusive. To uncover the molecular systems underlying GH deficiency in IGHD2, we established IGHD2 model mice, which carry both wild-type and mutant copies of the humanGH1gene, replacing each of the endogenous mouseGhloci. Our IGHD2 model mice exhibited growth retardation associated with intact cellular architecture and mildly activated ER stress in the pituitary gland, caused by decreases in the growth hormone releasing hormone receptor (Ghrhr) andGhgene promoter activities. Decreases inGhrhrandGhpromoter activities were likely caused by reduced levels of nuclear CREB3L2, which was demonstrated to stimulate the activity of theGhrhrandGhpromoters. This is the firstin vivostudy revealing a novel molecular mechanism of GH deficiency in IGHD2, representing a new paradigm, differing from widely accepted models.
Dynamic Erasure of Random X-Chromosome Inactivation during iPSC Reprogramming
Authors: Janiszewski Adrian , Talon Irene , Song Juan , Geest Natalie De , To San Kit , Bervoets Greet , Marine Jean-Christophe , Rambow Florian , Pasque Vincent
Published: February 2019

Background

Induction and reversal of chromatin silencing is critical for successful development, tissue homeostasis and the derivation of induced pluripotent stem cells (iPSCs). X-chromosome inactivation (XCI) and reactivation (XCR) in female cells represent chromosome-wide transitions between active and inactive chromatin states. While XCI has long been studied and provided important insights into gene regulation, the dynamics and mechanisms underlying the reversal of stable chromatin silencing of X-linked genes are much less understood. Here, we use allele-specific transcriptomic approaches to study XCR during mouse iPSC reprogramming in order to elucidate the timing and mechanisms of chromosome-wide reversal of gene silencing.

Results

We show that XCR is hierarchical, with subsets of genes reactivating early, late and very late. Early genes are activated before the onset of late pluripotency genes activation and the complete silencing of the long non-coding RNA (lncRNA) Xist. These genes are located genomically closer to genes that escape XCI, unlike those reactivating late. Interestingly, early genes also show increased pluripotency transcription factor (TF) binding. We also reveal that histone deacetylases (HDACs) restrict XCR in reprogramming intermediates and that the severe hypoacetylation state of the Xi persists until late reprogramming stages.

Conclusions

Altogether, these results reveal the timing of transcriptional activation of mono-allelically repressed genes during iPSC reprogramming, and suggest that allelic activation involves the combined action of chromatin topology, pluripotency transcription factors and chromatin regulators. These findings are important for our understanding of gene silencing, maintenance of cell identity, reprogramming and disease.
Seismic on floating ice: data acquisition versus flexural wave noise
Authors: Johansen Tor Arne , Ruud Bent Ole , Tømmerbakke Ronny , Jensen Kristian
Published: February 2019

Geophysical surveying of the Arctic will become increasingly important in future prospecting and monitoring of the terrestrial and adjacent areas in this hemisphere. Seismic data acquired on floating ice are hampered with extensive noise due to ice vibrations related to highly dispersive ice flexural waves generated by the seismic source. Several experiments have been conducted on floating ice in van Mijenfjorden in Svalbard in the Norwegian Arctic to specifically analyse the extent of flexural waves recorded with various seismic receivers and sources deployed both on top of ice and in the water below. The data show that flexural waves are severely damped at 5 m or deeper below the ice and hydrophone data suffer less from these vibrations compared with data recorded on the ice. Aliasing of single receiver hydrophone data can to some extent be suppressed using an in‐line line source of detonating cord. Experiments on ice on shallow water show prominent guided wave modes often referred to as Scholte waves propagating along the seabed. In this case, both flexural and Scholte waves interfere and make a complicated pattern of coherent noise. On shallow water, the positioning and type of the seismic source must be evaluated with respect to the coherent noise generated by these waves. Geophone strings of 25 m effectively suppress both flexural and Scholte waves due to their relative short wavelengths. An airgun generates relative more low‐frequency energy than a surface source of detonating cord. Accordingly, seismic mapping of deep seismic horizons seem to be best achieved using geophone strings of such length and an airgun source. For shallow targets, the use of hydrophones in combination with detonating cord is an appropriate solution. Seismic surveying in the Arctic always have to follow environmental restrictions of not disturbing or harming wildlife and not causing permanent footprints into the vulnerable tundra, which implies that the choice of seismic acquisition strategy might occur as a trade‐off between optimum data quality and environmental constraints.
Spatial synchrony in sub‐arctic geometrid moth outbreaks reflects dispersal in larval and adult life cycle stages
Authors: Vindstad Ole Petter Laksforsmo , Jepsen Jane Uhd , Yoccoz Nigel Gilles , Bjørnstad Ottar N. , Mesquita Michel d. S. , Ims Rolf Anker
Published: February 2019

Spatial synchrony in population dynamics can be caused by dispersal or spatially correlated variation in environmental factors like weather (Moran effect). Distinguishing between these mechanisms is challenging for natural populations, and the study of dispersal‐induced synchrony in particular has been dominated by theoretical modelling and laboratory experiments.

The goal of the present study was to evaluate the evidence for dispersal as a cause of meso‐scale (distances of tens of kilometres) spatial synchrony in natural populations of the two cyclic geometrid moths Epirrita autumnata and Operophtera brumata in sub‐arctic mountain birch forest in northern Norway.

To infer the role of dispersal in geometrid synchrony, we applied three complementary approaches, namely estimating the effect of design‐based dispersal barriers (open sea) on synchrony, comparing the strength of synchrony between E. autumnata (winged adults) and the less dispersive O. brumata (wingless adult females), and relating the directionality (anisotropy) of synchrony to the predominant wind directions during spring, when geometrid larvae engage in windborne dispersal (ballooning).

The estimated effect of dispersal barriers on synchrony was almost three times stronger for the less dispersive O. brumata than E. autumnata. Inter‐site synchrony was also weakest for O. brumata at all spatial lags. Both observations argue for adult dispersal as an important synchronizing mechanism at the spatial scales considered. Further, synchrony in both moth species showed distinct anisotropy and was most spatially extensive parallel to the east–west axis, coinciding closely to the overall dominant wind direction. This argues for a synchronizing effect of windborne larval dispersal. Congruent with most extensive dispersal along the east–west axis, E. autumnata also showed evidence for a travelling wave moving southwards at a speed of 50–80 km/year.

Our results suggest that dispersal processes can leave clear signatures in both the strength and directionality of synchrony in field populations, and highlight wind‐driven dispersal as promising avenue for further research on spatial synchrony in natural insect populations.
Earthworm activity and availability for meadow birds is restricted in intensively managed grasslands
Authors: Onrust Jeroen , Wymenga Eddy , Piersma Theunis , Olff Han
Published: February 2019

Earthworms are an important prey for the endangered meadow birds of northwest Europe. Although intensive grassland management with high manure inputs generally promotes earthworm abundance, it may reduce the effective food availability for meadow birds through desiccation of the topsoil, which causes earthworms to remain deeper in the soil.

We studied the response of Red Worm Lumbricus rubellus, a detritivore, and Grey Worm Aporrectodea caliginosa, a geophage, to soil moisture profiles in the field and under experimental conditions. Surfacing earthworms were counted weekly in eight intensively managed grasslands (treated with high inputs of slurry by slit injection) with variable groundwater tables in the Netherlands. At each count, soil penetration resistance, soil moisture tension and groundwater level were measured, while air temperature and humidity were obtained from a nearby weather station. The response to variation in the vertical distribution of soil moisture was also experimentally studied in the two earthworm species.

In the field, earthworms’ surfacing activity at night was negatively associated with soil moisture tension and positively by relative air humidity. Surprisingly, there was no effect of groundwater level; an important management variable in meadow bird conservation. Under experimental conditions, both L. rubellus and A. caliginosa moved to deeper soil layers (>20 cm) in drier soil moisture treatments, avoiding the upper layer when moisture levels dropped below 30%.

Synthesis and applications. We propose that in intensively managed grasslands with slurry application, topsoil desiccation reduces earthworm availability for meadow birds. This can be counteracted by keeping soil moisture tensions of the top soil above −15 kPa. We suggest that the late raising of groundwater tables in spring and the disturbance of the soil by slit injection of slurry increase topsoil desiccation. This decreases earthworm availability when it matters most for breeding meadow birds. Meadow bird conservation will benefit from revised manure application strategies that promote earthworm activity near or at the soil surface.
Divergent fire management leads to multiple beneficial outcomes for butterfly conservation in a production mosaic
Authors: Gaigher René , Pryke James S. , Samways Michael J.
Published: February 2019

Fire is an intrinsic component of many natural ecosystems. In human‐modified landscapes that occur in fire‐driven ecosystems, it can be difficult to make fire management decisions, as there must be a trade‐off between ideal conservation management and the practicalities of management in an altered landscape.

We assess how biodiversity is influenced by differences in fire regime in a landscape fragmented by timber production. Here, optimal fire management for maintaining grassland integrity is not always possible, due to logistical constraints and fire risk to plantations. We investigate thicket establishment arising from reduced fire frequency, and how this affects butterfly diversity, assemblage structure, indicator species and species associations to larval host plants with different growth forms. Butterflies were sampled along a gradient of woodiness in large‐scale conservation corridors that separate timber compartments.

The two extreme stages along the successional gradient, recently burned grassland and natural forests, supported relatively diverse and complementary butterfly assemblages. Grassland corridors without fire for 2 years were as high in butterfly diversity and similar in composition to recently burned grasslands. However, corridors without fire for >5 years were encroached by thicket and supported lower butterfly diversity. Thicket, with its intermediate vegetation character, was poor habitat for species adapted to either open grassland or to forests. Also, thicket‐encroached areas carry high fire risk to plantations.

Synthesis and applications. In this fragmented, fire‐driven ecosystem, there is more than one burning strategy for achieving positive biodiversity outcomes. We recommend a divergent management approach that covers both extremes of the fire frequency continuum, with the choice depending on the stage of succession and management logistics for each site: (a) frequent burning to prevent woody encroachment in less‐encroached, logistically easier sites or (b) letting succession run its course through thicket to forest by excluding fire in heavily encroached, logistically challenging sites. Both options are practicable and maintain biotopes that have high value for butterfly conservation and low fire risk to plantations. This divergent management approach is a flexible strategy that benefits both conservation and commercial interests across fire‐prone plantation mosaics.
Divergent responses to climate change and disturbance drive recruitment patterns underlying latitudinal shifts of tree species
Authors: Boisvert‐Marsh Laura , Périé Catherine , de Blois Sylvie
Published: February 2019

Climate change is expected to result in a reorganization of the continental distribution of tree species. Recent shifts in distribution patterns have been reported, but it is not always clear how climate change influences these patterns locally, especially in relation to other disturbances.

We investigated latitudinal shifts of four ecologically important tree species between 1970 and 2014 within a study area that encompasses their northernmost range limit in northeastern North America (Quebec, Canada; ~761,000 km2). Changes in latitudinal limits were defined in relation to changes in tree saplings’ occurrence patterns within forest plots resampled over two time periods (1970–1977 and 2003–2014). By examining changes in the frequency of occurrences in different portions of the study area along a latitudinal gradient, we were able to identify spatially explicit patterns of loss or gain (sapling recruitment) resulting in the shifts observed. We then estimated the probability of observing a recruitment event in response to changes in climate, disturbance and their interaction, using a multimodel selection approach.

Latitudinal limits of all four species shifted northward, but these shifts resulted from different patterns of plot occurrence changes, depending on the species and the location examined. Greater recruitment at northern locations than at southern ones drove shifts for Acer saccharum Marsh., Fagus grandifolia Ehrh. and Acer rubrum L., but less so for Betula alleghaniensis Britt. Climate variables indicating changes in early or late growing season conditions were most often selected in models. Warming tended to reduce recruitment probability in the south but increase it in the north, leading to divergent responses for a given species across the study area. Disturbance effects were generally less important than climate change effects, as was their interaction.

Synthesis. Spatially explicit and divergent responses to climate change and disturbance drive recruitment patterns underlying latitudinal shifts of tree species. The importance of early‐ or late‐season climate variables points towards biological processes being affected at critical stages of the life cycle. Understanding the factors that influence species’ migration capacity in a changing climate is crucial to inform adaptive management and conservation practices.
Snail herbivory affects seedling establishment in a temperate forest in the Ozarks
Authors: Liang Anna J. , Stein Claudia , Pearson Eleanor , Myers Jonathan A. , Crandall Raelene M. , Mangan Scott A.
Published: February 2019

Species‐specific herbivores are hypothesized to maintain plant diversity by preventing the dominance of any one plant species. However, a large proportion of herbivores have wide host ranges, and these generalists could have similar effects on plant community composition if they exhibit differences in their host preference. Here, we coupled laboratory and field experiments to test whether a common forest‐understorey snail (Neohelix alleni), a generalist herbivore, has the potential to influence forest composition through differential preference of their plant hosts.

We first performed a cafeteria‐style experiment to test whether N. alleni showed feeding preferences among leaves of five tree species and one shrub common to temperate forests in Missouri, USA. We then conducted a factorial snail and deer exclusion experiment to decouple the effects of snail herbivory from those of white‐tailed deer on seedling establishment of 1‐month‐old newly germinated seedlings of these six woody species in the field. Finally, we examined whether variation in both snail feeding preference and experimentally measured effects of snails on seedling establishment across plant species were related to their relative abundance measured in a 12‐ha forest plot.

In the laboratory, we found that snails preferred leaves of woody species that were less abundant in the forests relative to those species that were more common. In the forest, we found that experimental exclusion of snails had a stronger positive effect on seedling above‐ground biomass and survival over a 1‐year period than did exclusion of deer. Plant species found to be more preferred in the laboratory were also those that had lower seedling establishment in the forest due to the negative effects of snails.

Synthesis. Collectively, our results suggest that greater susceptibility to snail herbivory limits seedling establishment, perhaps contributing to differences in tree species relative abundance. Although less appreciated than their insect and mammal counterparts, herbivory by snails may be significant drivers to the assembly of forest tree communities.
Responses of seedling growth and survival to post‐germination cotyledon removal: An investigation among seven oak species
Authors: Yi Xianfeng , Bartlow Andrew W. , Curtis Rachel , Agosta Salvatore J. , Steele Michael A.
Published: February 2019

Rodents regularly rely on emerged epicotyls to locate and remove cotyledons still containing valuable nutrients. However, the extent to which acorn characteristics influence tolerance to post‐germination predation has received little attention.

Here, we investigated the impact of cotyledon removal following epicotyl emergence on seedling performance and survival of seven oak (Quercus) species. We imitated cotyledon predation at different stages of seedling establishment and development in order to detect effects on seedling height, leaf number and tissue/component mass.

Seedling growth and survival were negatively affected by cotyledon loss regardless of oak species. However, these negative effects decreased as the epicotyl length at which cotyledons were removed increased. We also found that there was a threshold epicotyl length above which seedling survival and performance were relatively unaffected in white oak species compared to red oak species.

Following cotyledon removal, early germinating white oak (section Quercus) seedlings survived and/or grew better than the late germinating red oak (section Lobatae) seedlings. This was likely caused by a difference in dependence on cotyledon reserves, which ultimately affected the ability of seedlings to tolerate cotyledon removal.

Synthesis. From an evolutionary perspective, this is likely to follow from the early germination in white oaks and the ability of seed consumers to locate young seedlings from the emerging epicotyls. Our study has implications for forest regeneration by suggesting additional opportunities for white oak species to establish following epicotyl emergence. Future studies should consider quantifying the rates of post‐germination cotyledon loss.
The heterogeneous effect of diversity: Ascriptive identities, class and redistribution in developed democracies
Authors: YAKTER ALON
Published: February 2019

The current consensus among comparative political scientists postulates that diverse democracies redistribute less than do homogeneous ones. However, whereas homogeneous democracies do redistribute more on average, diverse democracies exhibit high variation in redistributive outcomes. Why does ascriptive heterogeneity stifle redistribution in some cases but not in others? In this article, it is argued that diversity undermines redistributive outcomes when identity groups differ more starkly in their income levels. More importantly, under these conditions, the policy outcomes are not uniform: rather than general cutbacks, richer groups selectively under‐prioritise benefits and access for poorer, minority‐heavy groups while keeping their own redistributive interests protected. The result is not simply less redistribution aggregately, but a more exclusionary and regressive welfare state that prioritises the special needs of better‐off identity groups. Empirical support is found in these hypotheses using macro‐comparative panel data on multiple redistributive aspects in 22 developed democracies in the years 1980–2011. The article thus outlines a conditional and more nuanced relationship between diversity and redistributive outcomes than commonly assumed, as well as several broader lessons for research of identity politics and social policy.