bluuebunny/crossref_metadata_2025 huggingface dataset:
Dot1L-dependent H3K79 methylation facilitates histone variant H2A.Z exchange at DNA double strand breaks and is required for high fidelity, homology-directed DNA repair
Authors: Alvarez Nehemiah S. , Brachova Pavla , Fields Timothy A. , Fields Patrick E.
Published: February 2019

In eukaryotic cells, the homology-directed repair (HDR) and non-homologous end joining (NHEJ) pathways are required for the repair of DNA double strand breaks (DSB). The high-fidelity HDR pathway is particularly important for maintenance of genomic stability. In mammals, histone post-translational modifications and histone variant exchange into nucleosomes at sites of DSB generate an open chromatin state necessary for repair to take place. However, the specific contributions of histone modifications to histone variant exchange at DSB sites and the influence of these changes on the DNA repair process and genome stability are incompletely understood. Here we show that Dot1L-catalyzed methylation of H3 histone on lysine 79 (H3K79) is required for efficient HDR of DSB. In cells with DNA DSB either lacking Dot1L or expressing a methylation-dead Dot1L, there is altered kinetics of DNA repair factor recruitment, markedly decreased H2A.Z incorporation at DSB sites, and a specific and profound reduction in HDR, which results in significant genomic instability. These findings demonstrate a new role for Dot1L, identifying it as a critical regulator of the DNA repair process and a steward of genomic integrity.
Assaying how the success of phagocytosis depends on the mechanics of a large viscoelastic target
Authors: Davis-Fields M. , Bakhtiari L. , Kovach K. , Gordon V. D.
Published: February 2019

The state of the art does not provide a method for determining how the success of phagocytosis depends on the mechanics of a target that is much larger than the phagocytosing cell. We have developed such a method. We vary the elastic moduli of millimeter-sized abiotic gels that contain fluorescent beads to act as tracers for phagocytosis. We isolate human neutrophils, expose them to gels for one hour, and then measure what percentage of neutrophils contain beads – this is our metric for successful phagocytosis. Both increased polymer concentration in agarose gels and increased crosslinking density in alginate gels are associated with decreased success of phagocytosis. When we plot the percentage of neutrophils containing beads as a function of the gel elastic modulus, we find that data from both alginate and agarose gels collapse onto the same curve. This demonstrates the utility of our method as a way of measuring how the viscoelastic mechanics of a large target impact the success of phagocytosis.
Compound-V formations in shorebird flocks
Authors: Corcoran Aaron J. , Hedrick Tyson L.
Published: February 2019

Animal groups have emergent properties that result from simple interactions among individuals. However, we know little about why animals adopt different interaction rules because of sparse sampling among species. Here, we identify an interaction rule that holds across single and mixed-species flocks of four migratory shorebird species spanning a seven-fold range of body masses. The rule, aligning with a 1-wingspan lateral distance to nearest neighbors in the same horizontal plane, scales linearly with wingspan but is independent of nearest neighbor distance and neighbor species. This rule propagates outward to create a global flock structure that we term the compound-V formation. We propose that this formation represents an intermediary between the cluster flocks of starlings and the simple-V formations of geese and other large migratory birds. Analysis of individual wingbeat frequencies and airspeeds indicates that the compound-V formation may be an adaptation for aerodynamic flocking.
Morphological deconvolution of beta-lactam polyspecificity inE. coli
Authors: Godinez William J. , Chan Helen , Hossain Imtiaz , Li Cindy , Ranjitkar Srijan , Rasper Dita , Simmons Robert L. , Zhang Xian , Feng Brian Y.
Published: February 2019

Beta-lactam antibiotics comprise one of the earliest known classes of antibiotic therapies. These molsecules covalently inhibit enzymes from the family of penicillin-binding proteins, which are essential to the construction of the bacterial cell wall. As a result, beta-lactams have long been known to cause striking changes to cellular morphology. The exact nature of the changes tend to vary by the precise PBPs engaged in the cell since beta-lactams exhibit a range of PBP enzyme specificity. The traditional method for exploring beta-lactam polyspecificity is a gel-based binding assay which is low-throughput and typically runex situin cell extracts. Here, we describe a medium-throughput, image-based assay combined with machine learning methods to automatically profile the activity of beta-lactams inE. colicells. By testing for morphological change across a panel of strains with perturbations to individual PBP enzymes, our approach automatically and quantifiably relates different beta-lactam antibiotics according to their preferences for individual PBPs in cells. We show the potential of our approach for guiding the design of novel inhibitors towards different PBP-binding profiles by recapitulating the activity of two recently-reported PBP inhibitors.
pH controlled histone acetylation amplifies melanocyte differentiation program downstream of MITF
Authors: Raja Desingu Ayyappa , Gotherwal Vishvabandhu , Subramaniam Yogaspoorthi J , Sultan Farina , Vats Archana , Singh Archana , Sivasubbu Sridhar , Gokhale Rajesh S , Natarajan Vivek T
Published: February 2019

Tanning response and melanocyte differentiation are mediated by the central transcription factor MITF. Enigmatically, these involve rapid and selective induction of melanocyte maturation genes, while concomitantly maintaining the expression of other effectors. In this study using cell-based and zebrafish model systems, we elucidate a pH mediated feed-forward mechanism of epigenetic regulation that enables selective amplification of melanocyte maturation program. We demonstrate that MITF activation directly elevates the expression of Carbonic Anhydrase 14 (Ca14) enzyme. Nuclear localized Ca14 increases the intracellular pH, resulting in the activation of histone acetyl transferase activity of p300/CBP. In turn enhanced H3K27 histone acetylation marks of select differentiation genes facilitates their amplified expression by MITF. CRISPR-mediated targeted missense mutation of CA14 in zebrafish results in immature acidic melanocytes with decreased pigmentation, establishing the centrality of this mechanism in rapidly activating melanocyte differentiation. Thereby we reveal a novel epigenetic control through pH modulation that reinforces a deterministic cell fate by altering chromatin dynamics.
XIAP controls RIPK2 signaling by preventing its deposition in speck-like structures
Authors: Ellwanger Kornelia , Arnold Christine , Briese Selina , Kienes Ioannis , Pfannstiel Jens , Kufer Thomas A.
Published: February 2019

The receptor interacting serine/threonine kinase 2 (RIPK2) is essential for linking activation of the pattern recognition receptors NOD1 and NOD2 to cellular signaling events.

Recently, it was shown that RIPK2 forms higher order molecular structuresin vitro, which were proposed to activate signaling. Here, we demonstrate that RIPK2 forms detergent insoluble complexes in the cytosol of host cells upon infection with invasive enteropathogenic bacteria. Formation of these structures occurred after NF-κB activation and depends on the CARD of NOD1 or NOD2. Complex formation upon activation was dependent on RIPK2 autophosphorylation at Y474 and influenced by phosphorylation at S176. Inhibition of activity of the cIAP protein XIAP induced spontaneous complex formation of RIPK2 but blocked NOD1-dependet NF-κB activation. Using immunoprecipitation, we identified 14-3-3 proteins as novel binding partners of non-activated RIPK2, whereas complexed RIPK2 was bound by the prohibitin proteins Erlin-1 and Erlin-2.

Taken together, our work reveals novel roles of XIAP, 14-3-3 and Erlin proteins in the regulation of RIPK2 and expands our knowledge on the function of RIPK2 posttranslational modifications in NOD1/2 signaling.
Ionomycin Ameliorates Hypophosphatasia via Rescuing Alkaline Phosphatase Deficiency-mediated L-type Ca2+ Channel Internalization in Mesenchymal Stem Cells
Authors: Li Bei , He Xiaoning , Dong Zhiwei , Xuan Kun , Sun Wei , Gao Li , Liu Shiyu , Liu Wenjia , Hu Chenghu , Zhao Yimin , Shi Songtao , Jin Yan
Published: February 2019

Loss-of-function mutations in ALPL result in hypophosphatasia (HPP), an inborn error of metabolism that causes skeletal mineralization defect. In adults, main clinical involvement includes early loss of primary or secondary teeth, osteoporosis, bone pain, chondrocalcinosis, and fractures. However, guidelines for the treatment of adults with HPP are not available. Here, we show that ALPL deficiency caused reduction of intracellular Ca2+ influx resulting in osteoporotic phenotype due to downregulated osteogenic differentiation and upregulated adipogenic differentiation in both human and mouse BMSCs. To elevate intracellular level of calcium in bone marrow mesenchymal stem cells (BMSCs) by ionomycin treatment rescues the osteoporotic phenotype in alpl+/- mice and BMSC-specific (Prrx1-alpl-/-) conditional alpl knockout mice. Mechanistically, ALPL is required to maintain intracellular Ca2+ influx by regulating L-type Ca2+ channel trafficking via binding to the α2δ subunits, which regulates the internalization of L-type Ca2+ channel. Decreased Ca2+ flux inactivates Akt/GSK3β/β-catenin signaling pathway that regulates lineage differentiation of BMSCs. This study identifies a previous unknown role of ectoenzyme ALPL in maintenance of calcium channel trafficking to keep stem cell lineage differentiation and bone homeostasis. Accelerating Ca2+ flux through L-type Ca2+ channel by ionomycin treatment may be a promising therapeutic approach for adult HPP patients.

One Sentence Summary

ALP regulates internalization of L-Type Ca2+ Channel of BMSCs in Hypophosphatasia.
Exercise-induced enhancement of synaptic function triggered by the inverse BAR protein, Mtss1L
Authors: Chatzi Christina , Zhang Gina , Hendricks William , Chen Yang , Schnell Eric , Goodman Richard H. , Westbrook Gary L.
Published: February 2019

Exercise is a potent enhancer of learning and memory, yet we know little of the underlying mechanisms that likely include alterations in synaptic efficacy in the hippocampus. To address this issue, we exposed mice to a single episode of voluntary exercise, and permanently marked mature hippocampal dentate granule cells that were specifically activated during exercise using conditional Fos-TRAP mice. Only a few dentate granule cells were active at baseline, but two hours of voluntary exercise markedly increased the number of activated neurons. Activated neurons (Fos-TRAPed) showed an input-selective increase in dendritic spines and excitatory postsynaptic currents at 3 days post-exercise, indicative of exercise-induced structural plasticity. Laser-capture microdissection and RNASeq of activated neurons revealed that the most highly induced transcript was Mtss1L, a little-studied gene in the adult brain. Overexpression of Mtss1L in neurons increased spine density, leading us to hypothesize that its I-BAR domain initiated membrane curvature and dendritic spine formation. shRNA-mediated Mtss1L knockdown in vivo prevented the exercise-induced increases in spines and excitatory postsynaptic currents. Our results link short-term effects of exercise to activity-dependent expression of Mtss1L, which we propose as a novel effector of activity-dependent rearrangement of synapses.

One Sentence Summary

Single episodes of voluntary exercise induced a functional increase in hippocampal synapses mediated by activity-dependent expression of the BAR protein Mtss1L, acting as a novel early effector of synapse formation.
Adult-born neurons inhibit developmentally-born neurons in the dentate gyrus
Authors: Cahill Shaina P. , Martinovic Angela , Cole John Darby , Snyder Jason S.
Published: February 2019

During hippocampal-dependent memory formation, sensory signals from the neocortex converge in the dentate gyrus. It is generally believed that the dentate gyrus decorrelates inputs in order to minimize interference between codes for similar experiences, often referred to as pattern separation. Emerging evidence from mouse models suggests that adult-born neurons exert an inhibitory influence on the dentate gyrus, which may be important for maintaining the sparse code that is needed to form precise memories. However, since the dentate gyrus is composed of a heterogeneous population of cells that are born throughout life, it is unclear if newborn neurons inhibit all cells equally. We therefore investigated whether adult neurogenesis in rats modulates activity in dentate gyrus neurons that are born at the peak of early postnatal development. Adult neurogenesis was increased by subjecting rats to an alternating running and memantine treatment schedule, and it was decreased with a transgenic GFAP-TK rat model. Activity was measured by quantifying experience-induced Fos expression in BrdU+ cells. Consistent with an inhibitory role, enhancing neurogenesis blocked experience-dependent Fos expression in developmentally-born neurons and also in the broader granule cell population. In contrast, blocking neurogenesis did not significantly impact activity patterns. These results confirm previous work in mice and identify the developmentally-born population of neurons as a major target of neurogenesis-mediated inhibition. Treatments that target neurogenesis may therefore benefit disorders that are characterized by excitation-inhibition imbalance in the hippocampus, such as age-related memory impairments, fear and anxiety, and epilepsy.
A plant perspective on nitrogen cycling in the rhizosphere
Authors: Moreau Delphine , Bardgett Richard D. , Finlay Roger D. , Jones David L. , Philippot Laurent
Published: February 2019

Nitrogen is the major nutrient limiting plant growth in terrestrial ecosystems, and the transformation of inert nitrogen to forms that can be assimilated by plants is mediated by soil micro‐organisms.

The last decade has witnessed many significant advances in our understanding of plant–microbe interactions with evidence that plants have evolved multiple strategies to cope with nitrogen limitation by shaping and recruiting nitrogen‐cycling microbial communities. However, most studies have typically focused on the impact of plants on only one, or relatively few, processes within the nitrogen cycle.

This review synthesizes recent advances in our understanding of the various routes by which plants influence the availability of nitrogen via an array of interactions with different guilds of nitrogen‐cycling micro‐organisms. We also propose a plant trait‐based framework for linking plant nitrogen acquisition strategies to the activities of nitrogen‐cycling microbial guilds. In doing so, we provide a more comprehensive picture of the ecological relationships between plants and nitrogen‐cycling micro‐organisms in terrestrial ecosystems.

Finally, we identify previously overlooked processes within the nitrogen cycle that could be targeted in future research and be of interest for plant health or for improving plant nitrogen acquisition, while minimizing nitrogen inputs and losses in sustainable agricultural systems.

A plain language summary is available for this article.
Live fast, don't die young: Survival–reproduction trade‐offs in long‐lived income breeders
Authors: Culina Antica , Linton Danielle Marie , Pradel Roger , Bouwhuis Sandra , Macdonald David W.
Published: February 2019

Trade‐offs between survival and reproduction are at the core of life‐history theory, and essential to understanding the evolution of reproductive tactics as well as population dynamics and stability. Factors influencing these trade‐offs are multiple and often addressed in isolation. Further problems arise as reproductive states and survival in wild populations are estimated based on imperfect and potentially biased observation processes, which might lead to flawed conclusions.

In this study, we aimed at elucidating trade‐offs between current reproduction (both pregnancy and lactation), survival and future reproduction, including the specific costs of first reproduction, in long‐lived, income breeding small mammals, an under‐studied group.

We developed a novel statistical framework that encapsulates the breeding life cycle of females, and accounts for incomplete information on female pregnancy and lactation and imperfect and biased recapture rates. We applied this framework to longitudinal data on two sympatric, closely related bat species (Myotis daubentonii and M. nattereri).

We revealed the existence of several, to our knowledge previously unknown, trends in survival and breeding of these closely related, sympatric species and detected remarkable differences in their age and costs of first reproduction, as well as their survival–reproduction trade‐offs.

Our results indicate that species with this type of life history exhibit a mixture of patterns expected for long‐lived and short‐lived animals, and between income and capital breeders. Thus, we call for more studies to be conducted in similar study systems, increasing our ability to fully understand the evolutionary origin and fitness effects of trade‐offs and senescence.
Species asynchrony and response diversity determine multifunctional stability of natural grasslands
Authors: Sasaki Takehiro , Lu Xiaoming , Hirota Mitsuru , Bai Yongfei
Published: February 2019

A growing body of empirical evidence has suggested that biodiversity affects the simultaneous performance of multiple ecosystem functions (i.e. ecosystem multifunctionality). Given increasing environmental variability and uncertainty under global change, an emerging question is how biodiversity influences the stability of multiple functions (i.e. multifunctional stability). We currently know little, however, about the determinants and mechanisms of multifunctional stability, which is of practical importance for ensuring the sustainable provision of multiple functions.

Here, we examined mechanisms contributing to stability (quantified as the ratio of the mean to the standard deviation) of multiple functions related to ecosystem productivity and carbon sequestration, including plant above‐ground and below‐ground productivity, litter production, gross primary productivity and ecosystem respiration, in a large grassland biodiversity experiment in Inner Mongolia.

We found that community‐wide species asynchrony was a strong driver to stabilize multiple functions. Community‐wide asynchrony mediated the positive effects of species richness and response diversity (describing how species with similar effects on ecosystem function respond differently to environmental change) on multifunctional stability. However, species richness had a negative direct effect on multifunctional stability because, although it increased the averaged temporal mean of multiple functions, it strongly increased the averaged temporal standard deviation of multiple functions. The overall effects of species richness on multifunctional stability were thus negative, whereas those of response diversity were positive.

Synthesis. The studied ecosystem functions related to ecosystem productivity and carbon sequestration are important in natural grasslands across the world. We conclude that species asynchrony and response diversity, rather than species richness, are key to the ecosystem multifunctional stability. The loss of response diversity and compensatory mechanisms would likely reduce the long‐term sustainability of grasslands in the face of global change.
The individual and combined effects of snowmelt timing and frost exposure on the reproductive success of montane forbs
Authors: Pardee Gabriella L. , Jensen Isaac O. , Inouye David W. , Irwin Rebecca E.
Published: February 2019

Changes from historic weather patterns have affected the phenology of many organisms world‐wide. Altered phenology can introduce organisms to novel abiotic conditions during growth and modify species interactions, both of which could drive changes in reproduction.

We explored how climate change can alter plant reproduction using an experiment in which we manipulated the individual and combined effects of snowmelt timing and frost exposure, and measured subsequent effects on flowering phenology, peak flower density, frost damage, pollinator visitation and reproduction of four subalpine wildflowers. Additionally, we conducted a pollen‐supplementation experiment to test whether the plants in our snowmelt and frost treatments were pollen limited for reproduction. The four plants included species flowering in early spring to mid‐summer.

The phenology of all four species was significantly advanced, and the bloom duration was longer in the plots from which we removed snow, but with species‐specific responses to snow removal and frost exposure in terms of frost damage, flower production, pollinator visitation and reproduction. The two early blooming species showed significant signs of frost damage in both early snowmelt and frost treatments, which negatively impacted reproduction for one of the species. Further, we recorded fewer pollinators during flowering for the earliest‐blooming species in the snow removal plots. We also found lower fruit and seed set for the early blooming species in the snow removal treatment, which could be attributed to the plants growing under unfavourable abiotic conditions. However, the later‐blooming species escaped frost damage even in the plots where snow was removed, and experienced increased pollinator visitation and reproduction.

Synthesis. This study provides insight into how plant communities could become altered due to changes in abiotic conditions, and some of the mechanisms involved. While early blooming species may be at a disadvantage under climate change, species that bloom later in the season may benefit from early snowmelt, suggesting that climate change has the potential to reshape flowering communities.
Effect of lianas on forest‐level tree carbon accumulation does not differ between seasons: Results from a liana removal experiment in Panama
Authors: van der Heijden Geertje M. F. , Powers Jennifer S. , Schnitzer Stefan A.
Published: February 2019

Lianas are prevalent in Neotropical forests, where liana‐tree competition can be intense, resulting in reduced tree growth and survival. The ability of lianas to grow relative to trees during the dry season suggests that liana‐tree competition is also strongest in the dry season. If correct, the predicted intensification of the drying trend over large areas of the tropics in the future may therefore intensify liana‐tree competition resulting in a reduced carbon sink function of tropical forests. However, no study has established whether the liana effect on tree carbon accumulation is indeed stronger in the dry than in the wet season.

Using 6 years of data from a large‐scale liana removal experiment in Panama, we provide the first experimental test of whether liana effects on tree carbon accumulation differ between seasons. We monitored tree and liana diameter increments at the beginning of the dry and wet season each year to assess seasonal differences in forest‐level carbon accumulation between removal and control plots.

We found that median liana carbon accumulation was consistently higher in the dry (0.52 Mg C ha−1year−1) than the wet season (0.36 Mg C ha−1year−1) and significantly so in three of the years. Lianas reduced forest‐level median tree carbon accumulation more severely in the wet (1.45 Mg C ha−1year−1) than the dry (1.05 Mg C ha−1year−1) season in all years. However, the relative effect of lianas was similar between the seasons, with lianas reducing forest‐level tree carbon accumulation by 46.9% in the dry and 48.5% in the wet season.

Synthesis.Our results provide the first experimental demonstration that lianas do not have a stronger competitive effect on tree carbon accumulation during the dry season. Instead, lianas compete significantly with trees during both seasons, indicating a large negative effect of lianas on forest‐level tree biomass increment regardless of seasonal water stress. Longer dry seasons are unlikely to impact liana‐tree competition directly; however, the greater liana biomass increment during dry seasons may lead to further proliferation of liana biomass in tropical forests, with consequences for their ability to store and sequester carbon.
Evaluation of the potentiating effects of antidepressants on the contractile response to noradrenaline in guinea pig urethra smooth muscles
Authors: Obara Keisuke , Imanaka Satoko , Fukuhara Hiroka , Yamaki Fumiko , Matsuo Kazuhiro , Yoshio Takashi , Tanaka Yoshio
Published: February 2019

We investigated the potential augmenting effects of 19 clinically available antidepressants on noradrenaline (NA)‐induced contractions in guinea pig urethra smooth muscle (USM). Concentration‐response curves for NA‐induced contractions in guinea pig USM strips were obtained in the absence or presence of selected antidepressants. Desipramine, an active metabolite of imipramine, produced a contraction and potentiated NA‐induced contraction at the distal urethra without affecting the proximal urethra. Further, nortriptyline and amoxapine, tricyclic antidepressants, produced a contraction and potentiated NA‐induced contraction at the distal urethra. NA‐induced contraction was unaffected or reduced by imipramine, clomipramine, trimipramine, and amitriptyline at the proximal and distal urethra. Maprotiline, a tetracyclic antidepressant, potentiated NA‐induced contraction at the distal urethra. NA‐induced contraction was unaffected by mianserin at the proximal and distal urethra. Paroxetine, a selective serotonin reuptake inhibitor (SSRI), potentiated NA‐induced contraction at the distal urethra, while NA‐induced contraction was unaffected by fluvoxamine, sertraline, and escitalopram at the proximal and distal urethra. Milnacipran, a serotonin‐noradrenaline reuptake inhibitor (SNRI), potentiated NA‐induced contraction at the proximal and distal urethra, whereas duloxetine potentiated it at the distal urethra. Mirtazapine slightly inhibited NA‐induced contraction at the distal urethra. Aripiprazole and sulpiride did not affect NA‐induced contractions at the proximal nor distal urethra. Trazodone inhibited NA‐induced contraction at both urethras. Desipramine, nortriptyline, amoxapine, maprotiline, paroxetine, milnacipran, and duloxetine likely induce urinary disturbance by increasing urethral resistance and augmenting NA‐induced contraction, which should be carefully considered when delivering guidance for drug administration to patients.
Isolation or interaction: healthcare provider experience of design change
Authors: VanHeuvelen Jane S.
Published: February 2019

Recent studies have drawn attention to the relationship between healthcare environments and patient outcomes. Yet, it remains unclear how changes in the design of healthcare facilities are experienced by providers. To understand this relationship, this study employs an inhabited institutionalist theoretical frame to assess longitudinal ethnographic and interview data collected at a neonatal intensive care unit (NICU) as it transformed from an open‐bay unit, to one with single‐patient rooms. Findings show that changing the structure of the NICU interfered with the original local organisational culture of collaboration. While providers actively worked to maintain the original culture, their success in doing so was mediated by the built environment. Responding to the new space, practitioners developed new practices. Some of the practices (such as doorway discussions and increased individual assessments) directly undermined the original organisational culture, whereas others (hallway hangouts and calling out) worked to transpose the original culture into the new space. These findings call for greater attention to the effect of physical space on organisational culture.
Economic grievances and political protest
Authors: KURER THOMAS , HÄUSERMANN SILJA , WÜEST BRUNO , ENGGIST MATTHIAS
Published: February 2019

How do economic grievances affect citizens’ inclination to protest? Given rising levels of inequality and widespread economic hardship in the aftermath of the Great Recession, this question is crucial for political science: if adverse economic conditions depress citizens’ engagement, as many contributions have argued, then the economic crisis may well feed into a crisis of democracy. However, the existing research on the link between economic grievances and political participation remains empirically inconclusive. It is argued in this article that this is due to two distinct shortcomings, which are effectively addressed by combining the strengths of political economy and social movement theories. Based on ESS and EU‐SILC data from 2006–2012, as well as newly collected data on political protest in 28 European countries, a novel, more fine‐grained conceptualisation of objective economic grievances considerably improves our understanding of the direct link between economic grievances and protest behaviour. While structural economic disadvantage (i.e., the level of grievances) unambiguously de‐mobilises individuals, the deterioration of economic prospects (i.e., a change in grievances) instead increases political activity. Revealing these two countervailing effects provides an important clarification that helps reconcile many seemingly conflicting findings in the existing literature. Second, the article shows that the level of political mobilisation substantially moderates this direct link between individual hardship and political activity. In a strongly mobilised environment, even structural economic disadvantage is no longer an impediment to political participation. There is a strong political message in this interacting factor: if the presence of organised and visible political action is a decisive signal for citizens that conditions the micro‐level link between economic grievances and protest, then democracy itself – that is, organised collective action – can help sustain political equality and prevent the vicious circle of democratic erosion.
On prediction in political science
Authors: DOWDING KEITH , MILLER CHARLES
Published: February 2019

This article discusses recent moves in political science that emphasise predicting future events rather than theoretically explaining past ones or understanding empirical generalisations. Two types of prediction are defined: pragmatic, and scientific. The main aim of political science is explanation, which requires scientific prediction. Scientific prediction does not necessarily entail pragmatic prediction nor does it necessarily refer to the future, though both are desiderata for political science. Pragmatic prediction is not necessarily explanatory, and emphasising pragmatic prediction will lead to disappointment, as it will not always help in understanding how to intervene to change future outcomes, and policy makers are likely to be disappointed by its time‐scale.
Responding to the crisis: Eurosceptic parties of the left and right and their changing position towards the European Union
Authors: BRAUN DANIELA , POPA SEBASTIAN ADRIAN , SCHMITT HERMANN
Published: February 2019

At the time of the election of the European Parliament (EP) in 2014, the European Union (EU) was heavily affected by a multifaceted crisis that had – and still has – far‐reaching implications for the political system of its member countries, but also for the European level of governance. Against the background of the strong Eurosceptic vote in the 2014 EP elections, this study aims to investigate in which way Eurosceptic parties of the left and the right respond to the multiple crises of the EU. Using data from the Euromanifesto Project from 2004/2009 and 2014, changes in the party positions towards the EU are analysed in the shadow of the multiple crises and the reasons thereof are explored. The findings show a general anti‐European shift among the two types of Eurosceptic parties. Nevertheless, the changes in the EU polity tone are not determined by issue‐based repercussions of the multiple crises, but by the EU‐related evaluation – the polity mood – of the national citizenry. For far‐right Eurosceptic parties, the shift is moderated by the level of public support for EU integration in their national environment. Among far‐left Eurosceptic parties, by contrast, it is moderated by the more specific public attitudes about the monetary union policy of the EU. Consequently, political parties when drafting their manifestos for EP elections are not so much guided by the objective severity of political problems or by the evaluations of these problems by the citizenry. What matters in the end is the link that citizens themselves are able to establish between the severity of political problems, on the one hand, and the responsibility of the EU for these problems on the other. This has important consequences for understanding of the nature and substance of political responsiveness within the EU system of multilevel governance.
Updates of pancreatic neuroendocrine neoplasm in the 2017 World Health Organization classification
Authors: Leung Howard H.W. , Chan Anthony W.H.
Published: February 2019

The new 2017 World Health Organization (WHO) classification of pancreatic neuroendocrine neoplasms (PanNEN) modifies the previous 2010 version with new grading and staging systems to provide a better prognostic stratification and therapeutic guidance. The discovery of heterogeneity in WHO 2010 G3 category leads to the introduction of the new ‘well‐differentiated neuroendocrine tumor G3’ entity, which is distinct from the poorly‐differentiated pancreatic neuroendocrine carcinoma (PanNEC). The latest findings from molecular studies of PanNEN allow us to have a better understanding of respective biology of PanNET and PanNEC. This review aims at highlighting refinements in the 2017 classification and discusses some of the molecular updates in PanNEN.
The challenge for koala conservation on private land: koala habitat use varies with season on a fragmented rural landscape
Authors: Dargan J. R. , Moriyama M. , Mella V. S. A. , Lunney D. , Crowther M. S.
Published: February 2019

Land clearing for agriculture results in fragmented landscapes with diminished resources for wildlife. Habitat loss and fragmentation are widespread problems; however, their impacts are rarely assessed simultaneously at multiple spatial and temporal scales. We used a focal site, multiscale design to examine how landscape characteristics that affect the probability of koala Phascolarctos cinereus presence varies over multiple spatial and temporal scales in a fragmented rural landscape in north‐western New South Wales, Australia. We modelled the effect of variables representing landscape characteristics at three spatial extents – transect, patch and site – over three seasonal periods (mid‐spring, late‐spring and mid‐summer). Koala activity level (as determined by faecal pellets) varied between surveys, and identifies short‐term seasonal changes in habitat use. Koala presence had the strongest association with patch scale variables (habitat suitability, soil fertility and patch area). Temporal variation in the effect of tree and landscape characteristics on koala presence highlights the limitations of surveys at a single point in time, and emphasizes that further research is needed to advance our understanding of what drives temporal variation in koala habitat use at multiple spatial scales. Our results show that to arrest declining koala populations in rural agricultural landscapes, conservation and management plans must consider landscape scale processes over a variety of time scales, and engage stakeholders across multiple properties and tenures, to conserve both disturbed and suitable habitat on private land.
Identifying critical research gaps that limit control options for invertebrate pests in Australian grain production systems
Authors: Macfadyen Sarina , Moradi‐Vajargah Mona , Umina Paul , Hoffmann Ary , Nash Michael , Holloway Jo , Severtson Dusty , Hill Matthew , Van Helden Maarten , Barton Madeleine
Published: February 2019

Integrated Pest Management (IPM) is often described as a knowledge‐intensive approach to invertebrate pest management, requiring information on the biology, ecology and phenology of a pest combined with an understanding of the interactions between crop growth and pests and between pests and their natural enemies. We conducted a systematic quantitative literature review to summarise what is known about pest and natural enemy species common to Australian grain production systems, based on 1513 published and unpublished research studies. Drawing on this information, we address three issues: what are the knowledge gaps in relation to grain pests and their natural enemies, do these knowledge gaps limit the development of an IPM package for grain growers in Australia and what further ecological or biological information might growers require to enhance the use of IPM approaches for managing pests? The main gaps identified include a lack of understanding around specific factors that lead to pest outbreaks or factors that could be useful for predicting when and where pest outbreaks will occur in the future. Monitoring techniques for many pests are not well developed, and therefore, it is difficult to link the density recorded in a field with crop damage and yield loss and to develop economic thresholds that can be linked with intervention decisions. For most natural enemies, the impact in terms of reduction in pest numbers has not been quantified, with very few studies including both pests and natural enemies together. There is large variability in the level of control provided by natural enemies between years and regions, and the factors leading to this variability are not well understood. Finally, the lack of taxonomic resolution for individual species within groups is identified as a critical knowledge gap. We suggest that a more comprehensive fundamental knowledge base is required across the invertebrate community in grain systems aimed at reducing insect pest outbreaks, combined with a greater depth of understanding in monitoring strategies for pests that contribute to pesticide‐use decisions.
Mid‐ventricular obstructive hypertrophic cardiomyopathy with apical aneurysm: An important subtype of arrhythmogenic cardiomyopathy
Authors: Cui Li , Tse Gary , Zhao Zhiqiang , Bazoukis George , Letsas Konstantinos P. , Korantzopoulos Panagiotis , Roever Leonardo , Li Guangping , Liu Tong
Published: February 2019

Mid‐ventricular obstructive hypertrophic cardiomyopathy (MVOHCM) is an uncommon type of HCM. LV apical aneurysms are present in more than 20% MVOHCM cases and has been identified as an independent predictor of potentially lethal arrhythmic events, including non‐sustained or sustained ventricular tachycardia (VT), and ventricular fibrillation (VF), as well as SCD. Although the pathogenesis of LVA remains unknown, but it has been suggested that apical aneurysm may be secondary to the increased after‐load and high apical pressure arising from significant pressure gradient of the midventricular obstruction. The scarred rim of the aneurysm and the adjacent areas of LV myocardial fibrosis and consequent apical oxygen‐demand mismatch may be responsible for the formation of apical aneurysm. Recent electrophysiologic studies have demonstrated that the aneurysmal rim forms the primary culprit arrhythmogenic substrate for generation of monomorphic ventricular tachycardia leading to SCD, but the clinical significance of the size of aneurysm in relation to SCD remains unsettled. We summarized the clinical features of the patients with MVOHCM and apical aneurysms. Appropriate therapeutic interventions include ICD implantation, and early surgical intervention for gradient relief may be undertaken to relief the MVO.
Explaining the Success of the People’s Party: An Analysis of South Korea’s 2016 Legislative Elections
Authors: Rich Timothy S.
Published: February 2019

What explains the success of the upstart People’s Party in the 2016 Korean National Assembly election? Through preelection survey data, this article first identifies the demographic factors corresponding with support for the People’s Party and how this differs from preexisting parties. Next, it elaborates on how the two‐vote electoral system may have benefitted the People’s Party by encouraging voters to cast a party list vote for the party while casting a district vote for one of the larger parties, consistent with strategic voting. Further analysis shows that People’s Party supporters that intended to vote for their party’s district candidate, and thus cast a sincere rather than strategic district vote, were less likely than other partisans to split their votes across two parties.
Dynamics of Rivalry between Geographically Contiguous Regional Powers: The Case of Sino‐Indian Competition
Authors: Chand Bibek
Published: February 2019

The article analyzes the security dynamics of competing regional powers that have the added characteristic of geographic contiguity. It argues that geographic contiguity further exacerbates rivalry between two rising regional powers. As geographically contiguous regional powers attempt to build regional security frameworks as a step toward possible hegemony, they are bound to encounter conflicting interests. Due to the overwhelming decline of violent conquest and the extensive cost of undertaking war with another rising regional power, competing powers resort to soft balancing approaches in trying to constrain the rival’s strategic space. The Sino‐Indian relationship is used as a case study given their geographic contiguity, status as rising powers, and rivalrous bilateral relationship.
Lithium and the Woozle effect
Authors: Kelly Tammas
Published: February 2019

Objectives

Lithium is the oldest and most‐studied treatment for bipolar depression. Many treatment guidelines place lithium as a top treatment recommendation for bipolar depression; yet some guidelines do not recommend lithium at all. These discrepancies were explored by examining the following errors: the Woozle effect (evidence by citation), reference inflation (overreporting the findings of cited studies) and belief perseverance (maintaining a belief despite new contradictory evidence) as possible causes for these discrepancies.

Methods

Various search engines were used to find treatment guidelines for bipolar depression. The references cited in these guidelines were examined and analyzed in‐depth.

Results

Ten guidelines recommend lithium as a first‐line treatment for bipolar depression. Five did not recommend lithium at all for the treatment of bipolar depression. These discrepancies are remarkable. The references cited in the treatment guidelines were examined and do not favor lithium as a treatment for bipolar depression. The guidelines that favored lithium for the treatment of bipolar depression suffered numerous Woozle effects, reference inflation and belief perseverance are prevalent in guidelines that recommend lithium as a first‐line treatment. All three errors are principally slippery slopes. These errors do not involve a deliberate attempt to mislead and may reflect failures of the peer review process.

Conclusions

These errors may be common, as demonstrated in the case of lithium, interfering with our understanding and practice of evidence‐based medicine. Both authors and journals need to guard against these types of errors in order to achieve sound evidence‐based medical practices.
Law‐abiding organizational climates in developing countries: The role of institutional factors and socially responsible organizational practices
Authors: Mohammad Shoeb , Husted Bryan W.
Published: February 2019

The institutional environment of developing countries may lead firms to engage in unlawful firm conduct, which is a pervasive problem in this context. Our paper examines the effectiveness of organizational practices for ensuring that firms adhere to the law in the light of pressures from the institutional environment to be unlawful. Using the lens of anomie theory, we investigate: (a) the negative effect of aspects of the institutional context—regulatory burden and lack of industry munificence—on a law‐abiding climate, a type of organizational climate related to unlawful conduct, and (b) the role of socially responsible organizational practices in combating these negative effects. Survey data were collected from 118 firms and analysed using OLS moderated regression. Our results indicate that a manager's perceptions of regulatory burden and lack of industry munificence are negatively related to the extent to which the firm has a law‐abiding climate. Furthermore, our findings shed light on the ability of socially responsible practices to countervail this effect. While the negative effect of perceived regulatory burden on law‐abiding climate weakens when codes of ethics are used more extensively by a firm, it strengthens when firms hold a CSR certification. The latter finding may be due to the lack of enforcement associated with the specific certification considered in our study.
Additive effects of climate change and human hunting explain population decline and extinction in cave bears
Authors: Mondanaro Alessandro , Di Febbraro Mirko , Melchionna Marina , Carotenuto Francesco , Castiglione Silvia , Serio Carmela , Danisi Simone , Rook Lorenzo , Diniz‐Filho Jose Alexandre F. , Raia Pasquale
Published: February 2019

Cave bears (Ursus spelaeus) are an iconic component of the European late Quaternary Ice Age megafauna. Recent demographic analyses based on cave bear mtDNA sequences and refined radiocarbon dating indicate that cave bear population size and genetic diversity started to decline some 50 kilo years ago (kya). Hence, neither the coldest phase of the last glaciation (started some 24 kya), nor the colonization of Europe by Palaeolithic hunters (started some 45 kya) coincides with the beginning of population decline. Here, we reconstructed cave bear climatic niche evolution through time. Then, we performed spatially explicit population viability analyses to assess cave bear demographics through time in response to climatic changes, human effects on bear survival and their combination. We found that climate change was responsible for a 10‐fold decrease in cave bear population size after 40 kya. However, climate change on its own could not explain U. spelaeus extinction at 24 kya. Additional negative effects consistent with human population expansion are required to explain both U. spelaeus' retreat from eastern Europe since 40 kya and its final extinction.