bluuebunny/crossref_metadata_2025 huggingface dataset:
Reflection
Authors: Smithies Declan
Published: August 2019

Chapter 8 motivates accessibilism by appealing to William Alston’s hypothesis that the value of epistemic justification is tied to reflection, an activity that is the distinctive mark of persons who can be held responsible for their beliefs and actions. Section 8.1 argues that epistemic justification is what makes our beliefs stable under an idealized process of reflection. Section 8.2 uses this proposal in arguing for the JJ principle, which says that you have justification to believe a proposition if and only if you have justification to believe that you have justification to believe it. Sections 8.3–8.6 defend this proposal against a series of objections raised by Hilary Kornblith: the overintellectualization problem, the regress problem, the empirical problem, and the value problem. Section 8.7 concludes with some reflections on the debate between internalism and externalism about epistemic justification.
Higher-Order Evidence
Authors: Smithies Declan
Published: August 2019

Chapter 10 explores a puzzle about epistemic akrasia: if you can have misleading higher-order evidence about what your evidence supports, then your total evidence can make it rationally permissible to be epistemically akratic. Section 10.1 presents the puzzle and three options for solving it: Level Splitting, Downward Push, and Upward Push. Section 10.2 argues that we should opt for Upward Push: you cannot have misleading higher-order evidence about what your evidence is or what it supports. Sections 10.3 and 10.4 defend Upward Push against David Christensen’s objection that it licenses irrational forms of dogmatism in ideal and nonideal agents alike. Section 10.5 responds to his argument that misleading higher-order evidence generates rational dilemmas in which you’re guaranteed to violate one of the ideals of epistemic rationality. Section 10.6 concludes with some general reflections on the nature of epistemic rationality and the role of epistemic idealization.
Revolution and the Founding Era, 1763–1800
Authors: Harp Gillis J.
Published: August 2019

By the eve of the American Revolution, Loyalists were some of the most consistent defenders of the hallowed Christian commonwealth ideal, including the principle of social hierarchy. Among Patriots, certain Christian beliefs were also employed by conservatives such as John Dickinson and John Adams to apply the brakes to the more radical implications of the Revolution. Although the new Federal Constitution’s secular character rankled some conservatives, under the emerging First Party system, many High Federalists still stressed the political value of religion. Meanwhile, the radicalism of the French Revolution prompted conservatives to use explicitly Christian arguments to answer Enlightenment challenges to orthodox belief while painting their political opponents as infidels. By the turn of the nineteenth century, evangelicals were becoming more individualistic and less committed to the larger social and institutional project of conservatism.
The Gilded Age, 1865–1900
Authors: Harp Gillis J.
Published: August 2019

Richard Hofstadter argued that the new laissez-faire conservatism that became dominant during the last third of the nineteenth century was different from its predecessors in several respects, including in its secularism. Some popular preachers still attempted to accommodate laissez-faire principles and socially conservative evangelical Protestantism. A few conservatives refused to accept much of the new conservatism. These Protestant clerical intellectuals (both northern and southern) dissented from conservatism’s new orientation and offered a social theory still rooted in Protestant theology. This chapter highlights where these old-fashioned dissidents differed from their fellow conservatives and seeks also to describe their alternative conservative vision. Their story serves to clarify just how significant a shift occurred among conservatives during the Gilded Age and illuminates the last gasp of a more theocratic tradition among American Protestants.
The Early Twentieth Century, 1900–1945
Authors: Harp Gillis J.
Published: August 2019

Chapter 5 examines the first half of the twentieth century, focusing initially on the judicial and political critics of Progressivism. Although conservatives such as Justice David Brewer drew upon Christian elements in articulating their judicial theory, it was in a limited and circumscribed way. Similarly, political conservatives such as Elihu Root substituted a constitutional formalism and veneration of the Founders for the more theological approach of the Gilded Age dissenters. Meanwhile, leaders such as Presbyterian scholar John Gresham Machen helped draw evangelicals away from the older theocratic approach toward more libertarian views regarding politics and the state. Conservative responses to the Great Depression included Fundamentalists who viewed the New Deal apocalyptically and organizers of the Liberty League who warned of a coming totalitarianism. The modest connections established between Liberty Leaguers and evangelicals foreshadowed the deeper alliance that would profoundly shape the post–World War II conservative movement.
Postwar America, 1945–1970s
Authors: Harp Gillis J.
Published: August 2019

Chapter 6 examines the modern conservative movement and how the alliance of secular political elements with previously apolitical evangelicals slowly took shape during the thirty years following World War II. Richard Weaver’s Ideas Have Consequences (1948) served to provide some of the conservative movement’s essential historical and philosophical scaffolding, while Carl F. Henry’s Uneasy Conscience of Modern Fundamentalism (1947) encouraged evangelical political engagement. Oil tycoon and committed Presbyterian J. Howard Pew played a key role in galvanizing evangelicals by subsidizing Christianity Today and then linking them with political conservatives, being himself a former Liberty Leaguer and a fervent anticommunist. The presidential campaign of Barry Goldwater in 1964 stimulated evangelical political action and helped secure the essential union of more secular and openly religious conservatives. The Supreme Court’s controversial Roe v. Wade abortion decision in 1973 served to bolster this alliance by providing a moral issue that allowed some convergence and collaboration.
The Success and Failure of the Religious Right, 1970s–2010
Authors: Harp Gillis J.
Published: August 2019

Chapter 7 explores the successes and failures of what came to be called the Religious Right during the last third of the twentieth century and the early twenty-first century. Evangelical Protestantism contributed significantly to the moralism of the movement while lending apparent biblical sanction to already well-established conservative political positions such as limited government and free market economics. Participants in the Religious Right drew selectively from theologians such as Rousas John Rushdoony and Francis Schaeffer, but a nontheological pragmatism ultimately came to characterize the movement under television evangelists Jerry Falwell and Pat Robertson. With the election of Barack Obama in 2008, the emergence of the Tea Party movement confirmed how conventional conservative concerns about deficits and creeping socialism had successfully displaced ethical issues. This nontheological pragmatism can help explain the high levels of support for Donald Trump’s 2016 candidacy by white evangelicals.
Oral corticosteroid use during pregnancy and risk of preterm birth
Authors: Palmsten Kristin , Bandoli Gretchen , Vazquez-Benitez Gabriela , Xi Min , Johnson Diana L , Xu Ronghui , Chambers Christina D
Published: August 2019

Objective

To evaluate the associations between oral corticosteroid (OCS) dose early and late in pregnancy and preterm birth (PTB) among women with RA.

Methods

Pregnant women in the MotherToBaby Pregnancy Studies (2003–2014) with RA (n = 528) were included in the primary analysis. Information was collected by phone interview and from medical records. We estimated risk ratios (RR) for OCS dose trajectories and other disease-related medications before gestational day 140 and hazard ratios (HR) for time-varying exposures after gestational day 139.

Results

PTB risk was 15.5% overall. Compared with no OCS, PTB risk was increased in high (adjusted (a)RR: 4.77 (95% CI: 2.76, 8.26)) and medium (aRR: 1.81 (95% CI: 1.10, 2.97)) cumulative OCS dose trajectories during the first 139 gestational days. The low cumulative trajectory group was associated with an increased risk of PTB that was not statistically significant (aRR: 1.38 (95% CI: 0.79, 2.38)), and DMARDs were not associated with PTB (biologic DMARDs aHR: 1.08 (95% CI: 0.70, 1.66); non-biologic DMARDs aHR: 0.87 (95% CI: 0.55, 1.38)). OCS exposure to ⩾10 mg of prednisone equivalent daily dose after gestational day 139 vs none was associated with increased PTB rate (aHR: 2.45 (95% CI: 1.32, 4.56)), whereas <10 mg was associated with a modestly increased rate of PTB that was not statistically significant (aHR: 1.18 (95% CI: 0.60, 2.30)).

Conclusion

Higher OCS doses vs no OCS use, both earlier and later in pregnancy, were associated with an increase in PTB among women with RA.
Metabolome and Microbiome Signatures in the Roots of Citrus Affected by Huanglongbing
Authors: Padhi Emily M. T. , Maharaj Nilesh , Lin Shin-Yi , Mishchuk Darya O. , Chin Elizabeth , Godfrey Kris , Foster Elizabeth , Polek Marylou , Leveau Johan H. J. , Slupsky Carolyn M.
Published: August 2019

Huanglongbing (HLB) is a severe, incurable citrus disease caused by the bacterium ‘Candidatus Liberibacter asiaticus’ (CLas). Although citrus leaves serve as the site of initial infection, CLas is known to migrate to and colonize the root system; however, little is known about the impact of CLas infection on root metabolism and resident microbial communities. Scions of ‘Lisbon’ lemon and ‘Washington Navel’ orange grafted onto ‘Carrizo’ rootstock were grafted with either CLas-infected citrus budwood or uninfected budwood. Roots were obtained from trees 46 weeks after grafting and analyzed via 1H nuclear magnetic resonance spectroscopy to identify water-soluble root metabolites and high-throughput sequencing of 16S rRNA and ITS gene amplicons to determine the relative abundance of bacterial and fungal taxa in the root rhizosphere and endosphere. In both citrus varieties, 27 metabolites were identified, of which several were significantly different between CLas(+) and control plants. CLas infection also appeared to alter the microbial community structure near and inside the roots of citrus plants. Nonmetric multidimensional scaling (NMDS) and a principal coordinate analysis (PCoA) revealed distinct metabolite and microbial profiles, demonstrating that CLas impacts the root metabolome and microbiome in a manner that is variety-specific.
Histologic Changes During Treatment With Vismodegib in Locally Advanced Basal Cell Carcinoma: A Series of 19 Cases
Authors: Bancalari B. , Llombart B. , Serra-Guillén C. , Bernia E. , Requena C. , Nagore E. , Traves V. , Calomarde L. , Diago A. , Guillén C. , Sanmartín O.
Published: August 2019

Background:

There are no large series describing cutaneous histologic changes during treatment with vismodegib in locally advanced basal cell carcinoma (BCC).

Objective:

To analyze histologic changes in skin biopsy specimens from patients with locally advanced BCC treated with vismodegib.

Methods:

A descriptive, retrospective study of patients with locally advanced BCC treated with vismodegib between June 2012 and December 2017 at the Instituto Valenciano de Oncología, Spain. Nineteen patients were biopsied before and during the treatment with vismodegib, and we compared histologic changes observed.

Results:

Seven patients (37%) achieved complete response, which was characterized by replacement of tumor stroma with a hyaline scar, lymphocytic inflammatory infiltrate, keratin formation, and infundibular cysts. Twelve patients (63%) achieved partial response; 5 showed no phenotypic changes, whereas 7 showed histologic changes; 5 cases showed metatypical differentiation; and 2 cases presented squamous differentiation. We observed no cases of squamous cell carcinoma arising at vismodegib treatment sites and no association between initial histologic subtype and clinical response.

Limitations:

Many biopsy specimens were obtained by punch biopsy and may not be representative of the full tumors. We studied histologic changes only in complete and partial responses.

Conclusion:

Vismodegib can induce histologic changes toward metatypical or squamous differentiation of BCC in patients with partial response. Keratinizing phenomena were frequent, both in partial and complete response groups.
Erythema Nodosum, Early Stage—A Subcutaneous Variant of Leukocytoclastic Vasculitis? Clinicopathological Correlation in a Series of 13 Patients
Authors: Wilk Michael , Zelger Bettina G. , Hayani Kinan , Zelger Bernhard
Published: August 2019

Erythema nodosum (EN) is considered to represent a septal panniculitis. In a period from January 2000 until June 2018, we clinically and histopathologically investigated 124 patients with EN, 13 (10.5%) of them in an early stage demonstrating features of a leukocytoclastic vasculitis (LCV) around postcapillary venules of the subcutaneous fat. Three of these patients presented with EN on the lower legs and Sweet syndrome on the head/neck, arms, or trunk. 19.3% and 70.2% of patients demonstrated “classic” features of subacute and chronic forms of EN, respectively. Histopathologically, in cases of early EN apart from septally accentuated vascular damage and neutrophils with nuclear dust, eosinophils were evident in 5 specimens as well, in one case even with flame figures as seen in Wells syndrome. The inflammation spilled over to the dermis and lobular panniculus in 12 and 10 specimens, respectively. From the same time period and for comparison, we investigated 497 cases of “classic” LCV. Depending on the degree of vascular damage and the presence of neutrophils and nuclear dust, 65.8% presented with acute, 18.9% with subacute, and 15.3% with late-stage disease. In the latter, only a few neutrophils but rather lymphocytes and macrophages were present. Four hundred forty patients revealed an involvement of the deep dermis; of those, in 342, a septal inflammation was present as well, whereas in 94, the process was purely dermal. The subcutis was missing for evaluation in 61 cases. These results indicate a closer relationship between EN and LCV than previously considered.
The Feasibility to Isolate and Expand Tympanic Membrane Squamous Epithelium Stem Cells From Scarred Perforation Margins
Authors: Sagiv Doron , Harari-Steinberg Orit , Wolf Michael , Dekel Benjamin , Omer Dorit
Published: August 2019

Hypothesis:

The scarred rim of chronic tympanic membrane (TM) perforation contains keratinocytes with potential for regeneration while maintaining their morphological and genetic characteristics.

Background:

The squamous epithelium of the TM has a good regeneration capacity. Successful isolation and expansion of human TM keratinocytes (hTMKR) was reported from a full, en-bloc, healthy TM.

Methods:

Trimmed margins of the TM perforation (harvested during tympanoplasty) underwent enzymatic digestion (collagenase or trypsin) and were seeded either with serum-containing medium (SCM) or keratinocyte serum-free medium (KSFM) and progenitor cell growth medium (PR) (KSFM:PR, 1:1). Gene expression analysis by real-time qRT-PCR was used to compare between human TM cells derived from scarred perforation margins (hTMKR), normal human skin keratinocytes (NhSKR), and human fibroblasts.

Results:

Twelve patients were included in the study. In 9 of 12 cases (75%) single-cell isolation with fibroblastic or epithelial cell morphology (or both) was achieved. Cells seeded with KSFM:PR yielded epithelial morphology (hTMKR) while SCM culturing resulted in a fibroblastic morphology (hTMFib). Gene expression analysis revealed significant higher expression of VCAN (p = 0.002) and FOXC2 (p = 0.015) at the mRNA levels (normal hTMKR markers) in hTMKR compared to NhSKR. In addition, a comparison of gene expression between hTMKR and hTMFib revealed significantly higher levels of both VCAN (p = 0.045) and SLC6A14 (p = 0.036) among hTMKR.

Conclusion:

For the first time, we developed a protocol to isolate hTMKR from scarred TM perforation margins. Furthermore, we succeeded in achieving tissue expansion that preserved the characteristic of healthy TM cells. This study bridges “regenerative medicine” approach with clinical and surgical objectives.
A Skin Rejection Grading System for Vascularized Composite Allotransplantation in a Preclinical Large Animal Model
Authors: Etra Joanna W. , Grzelak Michael J. , Fidder Samuel A.J. , Kolegraff Keli , Bonawitz Steven , Shores Jaimie , Oh Byoungchol , Cooney Damon S. , Beck Sarah E. , Brandacher Gerald
Published: August 2019

Background.

The Banff Criteria have been accepted as a system for grading histological rejection in graft skin in human vascularized composite allotransplantation (VCA). Preclinical swine hindlimb transplantation models have an important role in translational studies in VCA. However, unified grading criteria for rejection in swine skin have not yet been established.

Methods.

Two hundred fourteen swine skin biopsy specimens were reviewed, including 88 native skin biopsies and 126 specimens from the skin component of heterotopic swine hindlimb transplants. Thorough review was performed in a blinded fashion by an expert veterinary pathologist with attention paid to the applicability of the Banff criteria as well as specific histologic characteristics and trends. Clinical and histopathologic rejection scores were then directly compared.

Results.

Two hundred fourteen specimens reviewed showed significant similarities between swine and human skin, as previously published. Notable swine-specific characteristics, including paucicellular infiltration with rare epidermal cell infiltration or necrosis, were accounted for in a proposed grading system that parallels the Banff Criteria.

Conclusions.

This comprehensive grading system, based on the Banff Classification for skin rejection in VCA, provides a standardized system for more accurate comparison of rejection in preclinical swine VCA models.
Wolbachia,Cardiniumand climate: an analysis of global data
Authors: Charlesworth J. , Weinert L. A. , Araujo E. V. , Welch J. J.
Published: August 2019

Bacterial endosymbionts are very common in terrestrial arthropods, but infection levels vary widely among populations. Experiments and within-species comparisons suggest that environmental temperature might be important in explaining this variation. To investigate the importance of temperature, at broad geographical and taxonomic scales, we extended a global database of terrestrial arthropods screened forWolbachiaandCardinium. Our final dataset contained data from more than 117 000 arthropods (over 2500 species) screened forWolbachiaand more than 18 000 arthropods (over 800 species) screened forCardinium, including samples from 137 different countries, with mean temperatures varying from −6.5 to 29.2°C. In insects and relatives,Cardiniuminfection showed a clear and consistent tendency to increase with temperature. ForWolbachia, a tendency to increase with temperature in temperate climates is counteracted by reduced prevalence in the tropics, resulting in a weak negative trend overall. We discuss the implications of these results for natural and introduced symbionts in regions affected by climate change.
Quantitative classification of vortical flows based on topological features using graph matching
Authors: Krueger Paul S. , Hahsler Michael , Olinick Eli V. , Williams Sheila H. , Zharfa Mohammadreza
Published: August 2019

Vortical flow patterns generated by swimming animals or flow separation (e.g. behind bluff objects such as cylinders) provide important insight to global flow behaviour such as fluid dynamic drag or propulsive performance. The present work introduces a new method for quantitatively comparing and classifying flow fields using a novel graph-theoretic concept, called a weighted Gabriel graph, that employs critical points of the velocity vector field, which identify key flow features such as vortices, as graph vertices. The edges (connections between vertices) and edge weights of the weighted Gabriel graph encode local geometric structure. The resulting graph exhibits robustness to minor changes in the flow fields. Dissimilarity between flow fields is quantified by finding the best match (minimum difference) in weights of matched graph edges under relevant constraints on the properties of the edge vertices, and flows are classified using hierarchical clustering based on computed dissimilarity. Application of this approach to a set of artificially generated, periodic vortical flows demonstrates high classification accuracy, even for large perturbations, and insensitivity to scale variations and number of periods in the periodic flow pattern. The generality of the approach allows for comparison of flows generated by very different means (e.g. different animal species).
Motion periodicity and bifurcation of a wave excited hopping ball
Authors: Ruhela Gaurang , DasGupta Anirvan
Published: August 2019

We consider the problem of a hopping ball excited by a travelling harmonic wave on an elastic surface. The ball, considered as a particle, is assumed to interact with the surface through inelastic collisions. The surface motion due to the wave induces a horizontal drift in the ball. The problem is treated analytically under certain approximations. The phase space of the hopping motion is captured by constructing a phase-velocity return map. The fixed points of the return map and its compositions represent periodic hopping solutions. The linear stability of the obtained periodic solution is studied in detail. The minimum frequency for the onset of periodic hops, and the subsequent loss of stability at the bifurcation frequency, have been determined analytically. Interestingly, for small values of wave amplitude, the analytical solutions reveal striking similarities with the results of the classical bouncing ball problem.
Cretaceous winged stick insects clarify the early evolution of Phasmatodea
Authors: Yang Hongru , Yin Xiangchu , Lin Xiaodan , Wang Chen , Shih Chungkun , Zhang Weiwei , Ren Dong , Gao Taiping
Published: August 2019

Wingless and shorter winged stick insects are very common today, but most known extinct stick insects had fully developed wings, leading to contentious affinities among the extinct winged and extant groups. We report herein three male winged stick insects, assigned to Pterophasmatidae fam. nov., from mid-Cretaceous Myanmar (Burmese) amber. Pterophasmatidae fam. nov. are regarded as transitional taxa from extinct winged to modern wingless and shorter winged stick insects based on their similar tegmina venation with extinct Susumanioidea and some body features the same as extant Phasmatodea. However, their symmetric phallic organs comprising two consistent phallomeres are different from those of all living groups. Phylogenetic analyses suggest that the extinct winged taxa, including the new family, are the stem groups of modern stick and leaf insects, and all of them constitute the clade of Phasmatodea. New findings indicate winged and wingless stick insects' morphologies diversified significantly during or before the mid-Cretaceous.
Frequent fires prime plant developmental responses to burning
Authors: Simpson Kimberley J. , Olofsson Jill K. , Ripley Brad S. , Osborne Colin P.
Published: August 2019

Coping with temporal variation in fire requires plants to have plasticity in traits that promote persistence, but how plastic responses to current conditions are affected by past fire exposure remains unknown. We investigate phenotypic divergence between populations of four resprouting grasses exposed to differing experimental fire regimes (annually burnt or unburnt for greater than 35 years) and test whether divergence persists after plants are grown in a common environment for 1 year. Traits relating to flowering and biomass allocation were measured before plants were experimentally burnt, and their regrowth was tracked. Genetic differentiation between populations was investigated for a subset of individuals. Historic fire frequency influenced traits relating to flowering and below-ground investment. Previously burnt plants produced more inflorescences and invested proportionally more biomass below ground, suggesting a greater capacity for recruitment and resprouting than unburnt individuals. Tiller-scale regrowth rate did not differ between treatments, but prior fire exposure enhanced total regrown biomass in two species. We found no consistent genetic differences between populations suggesting trait differences arose from developmental plasticity. Grass development is influenced by prior fire exposure, independent of current environmental conditions. This priming response to fire, resulting in adaptive trait changes, may produce communities more resistant to future fire regime changes.
A cluster of melioidosis infections in hatchling saltwater crocodiles (Crocodylus porosus) resolved using genome-wide comparison of a common north Australian strain of Burkholderia pseudomallei
Authors: Rachlin Audrey , Kleinecke Mariana , Kaestli Mirjam , Mayo Mark , Webb Jessica R. , Rigas Vanessa , Shilton Cathy , Benedict Suresh , Dyrting Kitman , Currie Bart J.
Published: August 2019

Burkholderia pseudomallei

is a Gram-negative saprophytic bacillus and the aetiological agent of melioidosis, a disease of public-health importance throughout Southeast Asia and northern Australia. Infection can occur in humans and a wide array of animal species, though zoonotic transmission and case clusters are rare. Despite its highly plastic genome and extensive strain diversity, fine-scale investigations into the population structure of

B. pseudomallei

indicate there is limited geographical dispersal amongst sequence types (STs). In the ‘Top End’ of northern Australia, five STs comprise 90 % of the overall abundance, the most prevalent and widespread of which is ST-109. In May 2016, ST-109 was implicated in two fatal cases of melioidosis in juvenile saltwater crocodiles at a wildlife park near Darwin, Australia. To determine the probable source of infection, we sampled the crocodile enclosures and analysed the phylogenetic relatedness of crocodile and culture-positive ST-109 environmental park isolates against an additional 135 ST-109

B. pseudomallei

isolates from the Top End. Collectively, our whole-genome sequencing (WGS) and pathology findings confirmed

B. pseudomallei

detected in the hatchling incubator as the likely source of infection, with zero SNPs identified between clinical and environmental isolates. Our results also demonstrate little variation across the ST-109 genome, with SNPs in recombinogenic regions and one suspected case of ST homoplasy accounting for nearly all observed diversity. Collectively, this study supports the use of WGS for outbreak source attribution in highly recombinogenic pathogens, and confirms the epidemiological and phylogenetic insights that can be gained from high-resolution sequencing platforms.
How Reliable are Prefrontal tDCS Effects – Zero–effects on the Keep–track Task?
Authors: Paunović Dunja , Purić Danka , Bjekić Jovana , Filipović Saša
Published: August 2019

Recent neuroimaging studies showed that in addition to the dorsolateral prefrontal cortex (dlPFC), the posterior parietal cortex (PPC) plays a significant role in higher cognitive processes such as executive functions. In this study we aimed to explore the neural underpinnings of executive function of updating by exploring the effects of transcranial direct current stimulation (tDCS) over dlPFC and PCC. Nineteen healthy right–handed participants took part in a cross–over sham–controlled experiment. All participants underwent three tDCS conditions (active tDCS over the left dlPFC; active tDCS over the left PPC; and sham) in counterbalanced order. Following tDCS participants completed the keep–track task, with parallel forms being used in different test–sessions. As a control measure, we used a choice reaction time task. Results showed no significant effects of tDCS regardless of the localization of stimulation. Our results are in contrast with results of other studies exploring prefrontal tDCS effects on updating and do not allow for deriving conclusions about the role of the left PPC in the ability to update information in working memory.
NbCycB2 represses Nbwo activity via a negative feedback loop in the tobacco trichome developmemt
Authors: Wu Minliang , Cui Yuchao , Ge Li , Cui Lipeng , Xu Zhichao , Zhang Hongying , Wang Zhaojun , Zhou Dan , Wu Shuang , Chen Liang , Cui Hong
Published: August 2019

The wo protein and its downstream gene,SlCycB2have been demonstrated to regulate the trichome development in tomato. It was shown that only gain-of-function mutant form ofwo, Wov(wo woolly motif mutant allele) could induce the increase of trichome density. However, it is still unclear the relationships between wo,WovandSlCycB2in trichome regulation. In this study, we demonstrated Nbwo (NbWov) directly regulated the expressionsNbCycB2by binding to the promoter ofNbCycB2and its genomic sequences. As a feedback regulation, NbCycB2 negatively regulates the trichome formation by repressing Nbwo activity at protein level. We further found that the mutations of Nbwo woolly motif could prevent repression of NbWovby NbCycB2, which results in the significant increase of activeNbwoproteins, trichome density and branches. Our results revealed a novel reciprocal mechanism betweenNbCycB2andNbwoduring the trichome formation inNicotiana benthamiana.

Highlight

NbCycB2is specifically expressed in trichomes ofNicotiana benthamianaand represses the Nbwo activity via a negative feedback loop in tobacco trichome developmemt.
PopDel identifies medium-size deletions jointly in tens of thousands of genomes
Authors: Niehus Sebastian , Jónsson Hákon , Schönberger Janina , Björnsson Eythór , Beyter Doruk , Eggertsson Hannes P. , Sulem Patrick , Stefánsson Kári , Halldórsson Bjarni V. , Kehr Birte
Published: August 2019

Thousands of genomic structural variants segregate in the human population and can impact phenotypic traits and diseases. Their identification in whole-genome sequence data of large cohorts is a major computational challenge. We describe a novel approach, PopDel, which jointly identifies deletions of about 500 to at least 10,000 bp in length in many genomes together. PopDel scales to tens of thousands of genomes as we demonstrate in evaluations on up to 49,962 genomes. We show that PopDel reliably reports common, rare and de novo deletions. On genomes with available high-confidence reference call sets PopDel shows excellent recall and precision. Genotype inheritance patterns in up to 6,794 trios indicate that genotypes predicted by PopDel are more reliable than those of previous SV callers. Furthermore, PopDel’s running time is competitive with the fastest tested previous tools. The demonstrated scalability and accuracy of PopDel enables routine scans for deletions in large-scale sequencing studies.
Evolutionary rescue is determined by differential selection on demographic rates and density dependence
Authors: Vinton Anna C , Vasseur David A
Published: August 2019

Accelerated rates of climate change are expected to either lead to populations adapting and persisting, or suffering extinction. Traditionally ecological models make extinction predictions based on how environmental change alters the intrinsic growth rate (r). However, these often ignore potential for evolutionary rescue, or to avoid extinction via adaptive evolution. Moreover, the environment may impose selective pressure on specific demographic rates (birth and death) rather than directly on r (the difference between the birth and death rates). Therefore, when we consider the potential for evolutionary rescue, populations with the same r can have different abilities to persist amidst environmental change. We can’t adequately understand evolutionary rescue without accounting for demography, and interactions between density dependence and environmental change. Using stochastic birth-death population models, we found evolutionary rescue more likely when environmental change alters birth rather than the death rate. Furthermore, species that evolve via density dependent selection are less vulnerable to extinction than species that undergo selection independent of population density. Resolving the key demographic factors affected by environmental change can lead to an understanding of how populations evolve to avoid extinction. By incorporating these considerations into our models we can better predict how species will respond to climate change.
Distinct features of nucleolus-associated domains in mouse embryonic stem cells
Authors: Bizhanova Aizhan , Yan Aimin , Yu Jun , Zhu Lihua Julie , Kaufman Paul D.
Published: August 2019

Background

Heterochromatin in eukaryotic interphase cells frequently localizes to the nucleolar periphery (nucleolus-associated domains, NADs) and the nuclear lamina (lamina-associated domains, LADs). Gene expression in somatic cell NADs is generally low, but NADs have not been characterized in mammalian stem cells.

Results

Here, we generated the first genome-wide map of NADs in mouse embryonic stem cells (mESCs) via deep sequencing of chromatin associated with biochemically-purified nucleoli. As we had observed in mouse embryonic fibroblasts (MEFs), the large Type I subset of NADs overlaps with constitutive LADs and is enriched for features of constitutive heterochromatin, including late replication timing and low gene density and expression levels. Conversely, the Type II NAD subset overlaps with loci that are not lamina-associated, but in mESCs, Type II NADs are much less abundant than in MEFs. mESC NADs are also much less enriched in H3K27me3 modified regions than are NADs in MEFs. Additionally, comparision of MEF and mESC NADs revealed enrichment of developmentally regulated genes in cell type-specific NADs. Together, these data indicate that NADs are a developmentally dynamic component of heterochromatin.

Conclusions

These studies implicate association with the nucleolar periphery as a mechanism for developmentally-regulated gene silencing, and will facilitate future studies of NADs during mESC differentiation.
Mnemonic prediction errors bias hippocampal states
Authors: Bein Oded , Duncan Katherine , Davachi Lila
Published: August 2019

In situations when our experience violates our predictions, it is adaptive to upregulate encoding of novel information, while down-weighting retrieval of erroneous memory predictions to promote an updated representation of the world. We asked whether mnemonic prediction errors promote distinct hippocampal processing ‘states’ by leveraging recent results showing that encoding and retrieval processes are supported by distinct patterns of connectivity, or ‘states’, across hippocampal subfields. During fMRI scanning, participants were cued to retrieve well-learned room-images and were then presented with either an image identical to the learned room or a modified version (1-4 changes). We found that CA1-entorhinal connectivity increased, and CA1-CA3 connectivity decreased, with the number of changes to the learned rooms. Further, stronger memory predictions measured in CA1 during the cue correlated with the CA1-entorhinal connectivity increase in response to violations. Our findings provide a mechanism by which mnemonic prediction errors may drive memory updating - by biasing hippocampal states.
Human Neocortical Neurosolver (HNN): A new software tool for interpreting the cellular and network origin of human MEG/EEG data
Authors: Neymotin Samuel A , Daniels Dylan S , Caldwell Blake , McDougal Robert A , Carnevale Nicholas T , Jas Mainak , Moore Christopher I , Hines Michael L , Hämäläinen Matti , Jones Stephanie R
Published: August 2019

Magneto- and electro-encephalography (MEG/EEG) non-invasively record human brain activity with millisecond resolution providing reliable markers of healthy and disease states. Relating these macroscopic signals to underlying cellular- and circuit-level generators is a limitation that constrains using MEG/EEG to reveal novel principles of information processing or to translate findings into new therapies for neuropathology. To address this problem, we built Human Neocortical Neurosolver (HNN, https://hnn.brown.edu) software. HNN has a graphical user interface designed to help researchers and clinicians interpret the neural origins of MEG/EEG. HNN’s core is a neocortical circuit model that accounts for biophysical origins of electrical currents generating MEG/EEG. Data can be directly compared to simulated signals and parameters easily manipulated to develop/test hypotheses on a signal’s origin. Tutorials teach users to simulate commonly measured signals, including event related potentials and brain rhythms. HNN’s ability to associate signals across scales makes it a unique tool for translational neuroscience research.
A new knockdown resistance (kdr) mutation, F1534L, in the voltage-gated sodium channel ofAedes aegypti, co-occurring with F1534C, S989P and V1016G
Authors: Kushwah Raja Babu S. , Kaur Taranjeet , Dykes Cherry L. , Kumar Ravi H. , Kapoor Neera , Singh Om P.
Published: August 2019

Background

Aedes aegyptiis a primary vector of dengue, chikungunya and zika infections in India. In the absence of specific drugs or safe and effective vaccines for these infections, their control relies mainly on vector control measures. The emergence of insecticide resistance in vectors, especially against pyrethroids, is a serious threat to the insecticide-based vector control programme. This study reports the presence of multiple knockdown resistance (kdr) mutations present in anAe. aegyptipopulation from Bengaluru (India), including a new mutation F1534L.

Methods

Aedes aegypticollected from Bengaluru were subjected to insecticide susceptibility tests with DDT, deltamethrin and permethrin. The DNA sequencing of partial domain II, III and IV of the voltage-gated sodium channel (VGSC) was performed to screenkdrmutations present in the population and PCR-based assays were developed for their detection. Genotyping ofkdrmutations was done using PCR-based assays, allelic frequencies were determined, and tests of genetic association ofkdrmutations with the insecticide resistance phenotype were performed.

Results

TheAe. aegyptipopulation were resistant to DDT, deltamethrin and permethrin. The DNA sequencing of the VGSC revealed the presence of fourkdrmutations, i.e., S989P and V1016G in domain II and two alternativekdrmutations F1534C and F1534L in domain III. Allele-specific PCR assays (ASPCR) were developed for the detection ofkdrmutations S989P and V1016G and an existing PCR-RFLP based strategy was modified for the genotyping of all three knownkdrmutations in domain III (F1534L, F1534C and T1520I). Genotyping ofAe. aegyptisamples collected between October 2014 and April 2015 revealed a moderate frequency of S989P/V1016G (18.27%) and F1534L (17.48%), a relatively high frequency of F1534C (50.61%) and absence of T1520I in the population. Mutations S989P and V1016G were in complete linkage disequilibrium in this population while they were in linkage equilibrium withkdrmutations F1534C and F1534L. The alleles F1534C and F1534L are genetically associated with permethrin resistance.

Conclusions

A newkdrmutation, F1534L, was found in anAe. aegyptipopulation from Bengaluru (India), co-occurring with the other three mutations S989P, V1016G and F1534C. The findings of a new mutation and development of PCR-based diagnostics have implications for insecticide resistance management. Monitoring of F1534L-kdrin other populations and studies on their functional role in altering neuro-sensitivity is warranted.
Genomic sequencing ofPhyllosticta citriasianaprovide insight into its conservation and diversification with closely relatedPhyllostictaspecies associated with citrus
Authors: Wang Mingshuang , Liu Bei , Ruan Ruoxin , Zeng Yibing , Luo Jinshui , Li Hongye
Published: August 2019

Phyllosticta citriasianais the causal agent of the pomelo tan spot. Here, we presented the ~34Mb genome ofP. citriasiana.The genome is organized in 92 contigs, encompassing 9202 predicted genes. Comparative genomic analyses with other twoPhyllostictaspecies (P. citricarpaandP. capitalensis) associated with citrus was conducted to understand their evolutionary conservation and diversification. Pairwise genome alignments revealed that these species are highly syntenic. All species encode similar numbers of CAZymes and secreted proteins. However, the molecular functions of the secretome showed that each species contains some enzymes with distinct activities. ThreePhyllostictaspecies shared a core set of 7261 protein families.P. capitalensishad the largest set of orphan genes (2040), in complete contrast to that ofP. citriasiana(371) andP. citricarpa(262). Most of the orphan genes were functionally unknown, but they contain a certain number of species-specific secreted proteins. A total of 23 secondary metabolites (SM) biosynthesis clusters were identified in the threePhyllostictaspecies, 21 of them are highly conserved among these species while the remaining 2 showed whole cluster gain and loss polymorphisms or gene content polymorphisms. Taken together, our study reveals insights into the genetic mechanisms of host adaptation ofPhyllostictaspecies associated with citrus and paves the way to identify effectors that function in infection of citrus plants.
Social interactions drive efficient foraging and income equality in groups of fish
Authors: Harpaz Roy , Schneidman Elad
Published: August 2019

The social interactions underlying group foraging and their benefits have been mostly studied using mechanistic models replicating qualitative features of group behavior, and focused on a single resource or a few clustered ones. Here, we tracked groups of freely foraging adult zebrafish with spatially dispersed food items and found that fish perform stereotypical maneuvers when consuming food, which attract neighboring fish. We then present a mathematical model, based oninferredfunctional interactions between fish, which accurately describes individual and group foraging of real fish. We show that these interactions allow fish to combine individual and social information to achieve near-optimal foraging efficiency and promote income equality within groups. We further show that the interactions that would maximize efficiency in these social foraging models depend on group size, but not on food distribution - suggesting that fish may adaptively pick the subgroup of neighbors they “listen to” to determine their own behavior.

Impact statement

Analysis and modeling of group behavior of adult zebrafish shows that a specialized social interaction mechanism increases foraging efficiency and equality within groups, under a variety of environmental conditions.
Adapting the Eysenck Personality Questionnaire-Revised Neuroticism scale for use in epidemiologic studies: A psychometric evaluation using item response theory in the UK Biobank
Authors: Bauermeister Sarah , Pflanz Chris Patrick , Gallacher John
Published: August 2019

Neuroticism has been described as a broad and pervasive personality dimension or ‘heterogeneous’ trait measuring components of mood instability, such as worry; anxiety; irritability; moodiness; self-consciousness and sadness. Consistent with depression and anxiety-related disorders, increased neuroticism places an individual vulnerable for other unipolar and bipolar mood disorders and therefore highly relevant in epidemiologic research. However, the measurement of neuroticism remains a challenge. We aimed to adapt the 12-item Eysenck Personality Questionnaire-Revised Neuroticism (EPQ-RN) scale for use in epidemiologic studies by identifying psychometrically efficient items using item response theory. The 12-item EPQ-RN scale was evaluated by estimating an IRT model on data from 401,527 UK Biobank participants aged 39 to 73 years (M= 56.41 years;SD= 8.06), 53.68% female. The IRT model yielded two item characteristics: item discrimination, an indicator of how well an item differentiates between respondents, and item difficulty, an indicator of the amount of the latent construct (neuroticism) needed to endorse an item. The EPQ-RN exhibited psychometric inefficiency with poor discrimination at extremes of the scale range. High and low scores are relatively poorly represented and uninformative suggesting that high neuroticism scores derived from the scale are a function of cumulative mid-range values. Following systematic item deletion, a 3-item scale was found to have high levels of discrimination, but offered a narrow range of difficulty i.e. was not sensitive to low levels of neuroticism. A 7-item scale was found to be most informative; providing high levels of discrimination across the range of neuroticism scores.
A new lineage of segmented RNA viruses infecting animals
Authors: Obbard Darren J. , Shi Mang , Roberts Katherine E. , Longdon Ben , Dennis Alice B.
Published: August 2019

Metagenomic sequencing has revolutionised our knowledge of virus diversity, with new virus sequences being reported faster than ever before. However, virus discovery from metagenomic sequencing usually depends on detectable homology: without a sufficiently close relative, so-called ‘dark’ virus sequences remain unrecognisable. An alternative approach is to use virus-identification methods that do not depend on detecting homology, such as virus recognition by host antiviral immunity. For example, virus-derived small RNAs have previously been used to propose ‘dark’ virus sequences associated with the Drosophilidae (Diptera). Here we combine published Drosophila data with a comprehensive search of transcriptomic sequences and selected meta-transcriptomic datasets to identify a completely new lineage of segmented positive-sense single-stranded RNA viruses that we provisionally refer to as the Quenyaviruses. Each of the five segments contains a single open reading frame, with most encoding proteins showing no detectable similarity to characterised viruses, and one sharing a small number of residues with the RNA-dependent RNA polymerases of single- and double-stranded RNA viruses. Using these sequences, we identify close relatives in approximately 20 arthropods, including insects, crustaceans, spiders and a myriapod. Using a more conserved sequence from the putative polymerase, we further identify relatives in meta-transcriptomic datasets from gut, gill, and lung tissues of vertebrates, reflecting infections of vertebrates or of their associated parasites. Our data illustrate the utility of small RNAs to detect viruses with limited sequence conservation, and provide robust evidence for a new deeply divergent and phylogenetically distinct RNA virus lineage.
m6A methylation potentiates cytosolic dsDNA recognition in a sequence-specific manner
Authors: Balzarolo Melania , Engels Sander , de Jong Anja J. , Franke Katka , van den Berg Timo K. , Janssen Edith M. , van Steensel Bas , Wolkers Monika C.
Published: August 2019

Nucleic acid sensing through pattern recognition receptors is critical for immune recognition of microbial infections. Microbial DNA is frequently methylated at the N6 position of adenines (m6A), a modification that is rare in mammalian host DNA. We show that m6A-methylation of 5’-GATC-3’ motifs augments the immunogenicity of double stranded (ds)DNA in macrophages and dendritic cells. Transfection with m6A-methylated DNA increased the expression of the activation markers CD69 and CD86, and of Ifnβ, iNos and Cxcl10 mRNA. Recognition of m6A DNA occurs independently of TLR and RIG-I signaling but requires STING, a key mediator of cytosolic DNA sensing. Intriguingly, the response to m6A DNA is sequence-specific. m6A is immunostimulatory in some motifs, but immunosuppressive in others, a feature that is conserved between mouse and human. In conclusion, epigenetic alterations of bacterial DNA are differentially perceived by innate cells, a feature that could potentially be used for the design of immune-modulating therapeutics.