bluuebunny/crossref_metadata_2025 huggingface dataset:
The 2018 outburst of BHXB H1743−322 as seen with MeerKAT
Authors: Williams D R A , Motta S E , Fender R , Bright J , Heywood I , Tremou E , Woudt P , Buckley D A H , Corbel S , Coriat M , Joseph T , Rhodes L , Sivakoff G R , van der Horst A J
Published: October 2019

In recent years, the black hole candidate X-ray binary system H1743−322 has undergone outbursts and it has been observed with X-ray and radio telescopes. We present 1.3 GHz MeerKAT radio data from the ThunderKAT Large Survey Project on radio transients for the 2018 outburst of H1743−322. We obtain seven detections from a weekly monitoring programme and use publicly available Swift X-ray Telescope and Monitor of All-sky X-ray Image data to investigate the radio/X-ray correlation of H1743−322 for this outburst. We compare the 2018 outburst with those reported in the literature for this system and find that the X-ray outburst reported is similar to previously reported ‘hard-only’ outbursts. As in previous outbursts, H1743−322 follows the ‘radio-quiet’ correlation in the radio/X-ray plane for black hole X-ray binaries, and the radio spectral index throughout the outburst is consistent with the ‘radio-quiet’ population.
Single lithium-ion channel polymer binder for stabilizing sulfur cathodes
Authors: Niu Chaoqun , Liu Jie , Qian Tao , Shen Xiaowei , Zhou Jinqiu , Yan Chenglin
Published: October 2019

Lithium–sulfur batteries have great potential for high-performance energy-storage devices, yet the severe diffusion of soluble polysulfide to electrolyte greatly limits their practical applications. To address the above issues, herein we design and synthesize a novel polymer binder with single lithium-ion channels allowing fast lithium-ion transport while blocking the shuttle of unnecessary polysulfide anions. In situ UV–vis spectroscopy measurements reveal that the prepared polymer binder has effective immobilization to polysulfide intermediates. As expected, the resultant sulfur cathode achieves an excellent specific capacity of 1310 mAh g−1 at 0.2 C, high Coulombic efficiency of 99.5% at 0.5 C after 100 cycles and stable cycling performance for 300 cycles at 1 C (1 C = 1675 mA g−1). This study reports a new avenue to assemble a polymer binder with a single lithium-ion channel for solving the serious problem of energy attenuation of lithium–sulfur batteries.
Open Options Education and Children’s Religious Upbringing: A Critical Review of Current Discussions Taking Place in the UK Parliament
Authors: Hill Ryan
Published: October 2019

Ensuring open minds and open options education has recently been suggested by the UK House of Lords as a State role that can and should override parents’ decisions in relation to their children’s religious upbringing and education. Yet the language used in their Lordship’s debates risks failing to respect the nature and purpose of legally enshrined parental rights in this area and of being perceived as potential bias that rests on a set of assumptions difficult to adequately determine. Through reference to various writings and case law on the interplay between parents’ rights relating to religious upbringing and the State’s obligations to education, along with an in-depth analysis of the notion of indoctrination, this article critiques their Lordships’ discussions over this complex and highly charged issue by highlighting some of the problems confronting their discussions.
Familial aggregation and heritability of ankylosing spondylitis – a Swedish nested case–control study
Authors: Morin Matilda , Hellgren Karin , Frisell Thomas
Published: October 2019

Objectives

AS is known to be a highly heritable disease, but previous studies on the magnitude of the familial aggregation and heritability of AS have been small and inconclusive, with familial relative risks ranging from 17 to 94. We aimed to improve estimates of these factors by studying families of all subjects diagnosed with AS in Sweden over a period of 16 years and to investigate if familial risks vary by sex or type of relative.

Methods

In a nested case–control study, we identified AS index patients from the National Patient Register (NPR) and the Swedish Rheumatology Quality Register (SRQ) between 2001 and 2016. Each index patient was matched on age and sex to up to 50 general population controls. First-degree relatives of index patients and controls were identified through the Multi-Generation Register, with disease status ascertained in the NPR and SRQ. Familial risks were defined as odds ratios (ORs) of having AS when exposed to a first-degree relative with AS, using conditional logistic regression.

Results

The overall familial OR for AS was 19.4 (95% CI 18.1, 20.8). Estimates were similar for different relative types and by sex, but having more than one affected relative resulted in a higher risk [OR 68.0 (95% CI 51.3, 90.1)]. Heritability, estimated by assuming sibling risks were completely due to genetics, was 77% (95% CI 73, 80).

Conclusion

Although the familial risk and heritability of AS are higher than for most other diseases, we report estimates that are substantially lower than commonly referenced numbers for AS from other populations.
Hidradenitis Suppurativa
Authors: Kawak Samer
Published: October 2019

Case Summary:

A 66-year-old obese (BMI 34) diabetic man, a former smoker who had quit 4 months ago, had a 20-year history of perianal, inguinal, and gluteal hidradenitis suppurativa. He presented to the office with persistent perianal and gluteal inflammation and drainage. He had had various surgical excisions of the affected area over the preceding 10 years. The patient was also following up with dermatology and was previously on doxycycline and infliximab with little improvement in his symptoms. On physical examination of his gluteal and perianal region, he had multiple areas of scarring and draining sinus tracts with significant induration (Figs. 1 and 2). The patient underwent extensive unroofing of the sinus tracts and excision of active disease (Fig. 3).
Spatial–Temporal Cluster Analysis of Childhood Cancer in California
Authors: Francis Stephen Starko , Enders Catherine , Hyde Rebecca , Gao Xing , Wang Rong , Ma Xiaomei , Wiemels Joseph L. , Selvin Steve , Metayer Catherine
Published: October 2019

Background:

The observance of nonrandom space–time groupings of childhood cancer has been a concern of health professionals and the general public for decades. Many childhood cancers are suspected to have initiated in utero; therefore, we examined the spatial–temporal randomness of the birthplace of children who later developed cancer.

Methods:

We performed a space–time cluster analysis using birth addresses of 5,896 cases and 23,369 population-based, age-, sex-, and race/ethnicity-matched controls in California from 1997 to 2007, evaluating 20 types of childhood cancer and three a priori designated subgroups of childhood acute lymphoblastic leukemia (ALL). We analyzed data using a newly designed semiparametric analysis program, ClustR, and a common algorithm, SaTScan.

Results:

We observed evidence for nonrandom space–time clustering for ALL diagnosed at 2–6 years of age in the South San Francisco Bay Area (ClustR P = 0.04, SaTScan P = 0.07), and malignant gonadal germ cell tumors in a region of Los Angeles (ClustR P = 0.03, SaTScan P = 0.06). ClustR did not identify evidence of clustering for other childhood cancers, although SaTScan suggested some clustering for Hodgkin lymphoma (P = 0.09), astrocytoma (P = 0.06), and retinoblastoma (P = 0.06).

Conclusions:

Our study provides evidence that childhood ALL diagnosed at 2–6 years and malignant gonadal germ cell tumors sporadically occurs in nonrandom space–time clusters. Further research is warranted to identify epidemiologic features that may inform the underlying etiology.
Development and Validation of a Google Street View Pedestrian Safety Audit Tool
Authors: Mooney Stephen J. , Wheeler-Martin Katherine , Fiedler Laura M. , LaBelle Celine M. , Lampe Taylor , Ratanatharathorn Andrew , Shah Nimit N. , Rundle Andrew G. , DiMaggio Charles J.
Published: October 2019

Background:

Assessing aspects of intersections that may affect the risk of pedestrian injury is critical to developing child pedestrian injury prevention strategies, but visiting intersections to inspect them is costly and time-consuming. Several research teams have validated the use of Google Street View to conduct virtual neighborhood audits that remove the need for field teams to conduct in-person audits.

Methods:

We developed a 38-item virtual audit instrument to assess intersections for pedestrian injury risk and tested it on intersections within 700 m of 26 schools in New York City using the Computer-assisted Neighborhood Visual Assessment System (CANVAS) with Google Street View imagery.

Results:

Six trained auditors tested this instrument for inter-rater reliability on 111 randomly selected intersections and for test–retest reliability on 264 other intersections. Inter-rater kappa scores ranged from −0.01 to 0.92, with nearly half falling above 0.41, the conventional threshold for moderate agreement. Test–retest kappa scores were slightly higher than but highly correlated with inter-rater scores (Spearman rho = 0.83). Items that were highly reliable included the presence of a pedestrian signal (K = 0.92), presence of an overhead structure such as an elevated train or a highway (K = 0.81), and intersection complexity (K = 0.76).

Conclusions:

Built environment features of intersections relevant to pedestrian safety can be reliably measured using a virtual audit protocol implemented via CANVAS and Google Street View.
Pancreatic Extracts for the Treatment of Diabetes (1889–1914): Acomatol
Authors: de Leiva-Hidalgo Alberto , de Leiva-Pérez Alejandra
Published: October 2019

Background:

Historical review on the early development of organotherapy for diabetes [pancreatic extracts (PE)] and its relationship with the social and political circumstances.

Areas of Uncertainty:

The diagnosis of diabetes relied only in the presence of glycosuria and cardinal symptoms. Blood glucose determinations were not regularly available, requiring large volumes for sampling. Micromethods for glycemia were developed just in the last years of the investigated period. Hypoglycemia remains undiscovered. Isolation and purification of PE were difficult tasks due to the unknown chemical structure of the antidiabetic hormone.

Data Sources:

(1) Berliner Medizinhistoriches Museum der Charité (Humboldt University). (2) GeDenKort Charité-Wissenschaft in Verantwortung. (3) Geheim Staatsarchiv Preuβischer Kulturbesitz. (4) Archival Collections, University of Toronto: Thomas Fisher Rare Book Library. Academy of Medicine Collection, F. G. Banting Papers, C. H. Best Papers, J. J. R. Macleod Papers. (5) National Library of Medicine: Pubmed search for the topic of history of insulin. History of Medicine-on syllabus archive. (6) Selected books: The Discovery of Insulin (M. Bliss); Diabetes, Its Medical and Cultural History (D. von Engelhardt); Brown-Séquard (M. J. Aminoff); Diabetes: The Biography (R. Tattersall); The Endocrine Organs (E. Schäfer); The Internal Secretions (E. Gley); Health, race and German politics between national unification and Nazism, 1870–1945 (P. Weindling).

Therapeutic Advances:

Demonstration that diabetes is a pancreatic disease. The outstanding progress of medical physiology led to the birth of endocrinology and the key concepts of homeostasis. Experimental scientists designed new procedures for complete pancreatectomy and elaboration of PE containing the antidiabetic principle. Organotherapy achieved complete success in the treatment of myxedema and partial success in the treatment of experimental and clinical diabetes.

Conclusions:

The organotherapy of diabetes was an obliged step to facilitate the identification of the antidiabetic hormone. Organotherapy of diabetes was a paradigm for the integration of basic and applied knowledge about hormone action and development of endocrine pharmacology.
Analysis of Soft Tissue Materials for Simulation Development
Authors: Caldwell Julia , Mooney James J.
Published: October 2019

Introduction

To meet unique demands and stretch budgets, simulations will often be made rather than purchased. Although 3-dimensional printing can be useful, there are significant physical limitations of these materials. This project is intended to begin examining the physical properties of materials used in casting/molding that may be useful for simulant soft tissue creation.

Methods

A variety of materials (foams and rubbers, urethanes and silicones, ballistic and food grade gels) were cast in standardized forms for analysis and visualized via computed tomography scanner and ultrasound (US). Each sample was also tested using 18ga and 22ga needles to determine force required for penetration.

Results

Silicone rubbers were generally well visualized via US, with computed tomography imaging showing between 100 and 200 Hounsfield units. Ballistic and food grade gels measured in the areas of −175 and 8 Hounsfield units, respectively, while being clear under US. Foams, particularly the urethane, demonstrated low Hounsfield units and were essentially opaque to US because of air cell artifact. Needle force requirements ranged from 0.05 to 23.34 N. Gels and foams were in the lower range, but there was overlap with the silicone. The use of additives in the silicones allowed for a wide range of needle forces and tactile experiences.

Conclusions

Silicone and urethane materials can mimic soft tissues, for both imaging and interventions. Although there is significant potential for independent production of custom, high-fidelity simulants, further work is required to identify preferable combinations of materials and optimal techniques for their use.
Escaping the evolutionary trap? Sex chromosome turnover in basilisks and related lizards (Corytophanidae: Squamata)
Authors: Nielsen Stuart V. , Guzmán-Méndez Irán Andira , Gamble Tony , Blumer Madison , Pinto Brendan J. , Kratochvíl Lukáš , Rovatsos Michail
Published: October 2019

Most pleurodont lizard families (anoles, iguanas and their relatives), with the exception of the basilisks and casquehead lizards (family Corytophanidae), share homologous XX/XY sex chromosomes, syntenic with chicken chromosome 15. Here, we used a suite of methods (i.e. RADseq, RNAseq and qPCR) to identify corytophanid sex chromosomes for the first time. We reveal that all examined corytophanid species have partially degenerated XX/XY sex chromosomes, syntenic with chicken chromosome 17. Transcriptomic analyses showed that the expression of X-linked genes in the corytophanid,Basiliscus vittatus,is not balanced between the sexes, which is rather exceptional under male heterogamety, and unlike the dosage-balanced sex chromosomes in other well-studied XX/XY systems, including the green anole,Anolis carolinensis. Corytophanid sex chromosomes may represent a rare example of a turnover away from stable, differentiated sex chromosomes. However, because of poor phylogenetic resolution among pleurodont families, we cannot reject the alternative hypothesis that corytophanid sex chromosomes evolved independently from an unknown ancestral system.
Optic flow cues help explain altitude control over sea in freely flying gulls
Authors: Serres Julien R. , Evans Thomas J. , Åkesson Susanne , Duriez Olivier , Shamoun-Baranes Judy , Ruffier Franck , Hedenström Anders
Published: October 2019

For studies of how birds control their altitude, seabirds are of particular interest because they forage offshore where the visual environment can be simply modelled by a flat world textured by waves then generating only ventral visual cues. This study suggests that optic flow, i.e. the rate at which the sea moves across the eye’s retina, can explain gulls’ altitude control over seas. In particular, a new flight model that includes both energy and optical invariants helps explain the gulls’ trajectories during offshore takeoff and cruising flight. A linear mixed model applied to 352 flights from 16 individual lesser black backed gulls (Larus fuscus) revealed a statistically significant optic flow set-point ofca25° s−1. Thereafter, an optic flow-based flight model was applied to 18 offshore takeoff flights from nine individual gulls. By introducing an upper limit in climb rate on the elevation dynamics, coupled with an optic flow set-point, the predicted altitude gives an optimized fit factor value of 63% on average (30–83% in range) with respect to the GPS data. We conclude that the optic flow regulation principle helps gulls to adjust their altitude over sea without having to directly measure their current altitude.
‘Data’ in the Royal Society's
Philosophical Transactions
, 1665–1886
Authors: Meyns Chris
Published: October 2019

Was there a concept of data before the so-called ‘data revolution’? This paper contributes to the history of the concept of data by investigating uses of the term ‘data’ in texts of the Royal Society's
Philosophical Transactions
for the period 1665–1886. It surveys how the notion enters the journal as a technical term in mathematics, and charts how over time it expands into various other scientific fields, including Earth sciences, physics and chemistry. The paper argues that in these texts the notion of data is not used merely as a rhetorical category, and also cannot strictly be identified with the category of evidence. Instead, the notion comes with an associated epistemic structure, one that is in line with its development from an early mathematical use.
miR-149-3p reverses CD8
+
T-cell exhaustion by reducing inhibitory receptors and promoting cytokine secretion in breast cancer cells
Authors: Zhang Meng , Gao Dian , Shi Yanmei , Wang Yifan , Joshi Rakesh , Yu Qiongfang , Liu Daheng , Alotaibi Faizah , Zhang Yujuan , Wang Hongmei , Li Qing , Zhang Zhu-Xu , Koropatnick James , Min Weiping
Published: October 2019

Blockade of inhibitory receptors (IRs) is one of the most effective immunotherapeutic approaches to treat cancer. Dysfunction of miRNAs is a major cause of aberrant expression of IRs and contributes to the immune escape of cancer cells. How miRNAs regulate immune checkpoint proteins in breast cancer remains largely unknown. In this study, downregulation of miRNAs was observed in PD-1-overexpressing CD8
+
T cells using miRNA array analysis of mouse breast cancer homografts. The data reveal that miR-149-3p was predicted to bind the 3'UTRs of mRNAs encoding T-cell inhibitor receptors PD-1, TIM-3, BTLA and Foxp1. Treatment of CD8
+
T cells with an miR-149-3p mimic reduced apoptosis, attenuated changes in mRNA markers of T-cell exhaustion and downregulated mRNAs encoding PD-1, TIM-3, BTLA and Foxp1. On the other hand, T-cell proliferation and secretion of effector cytokines indicative of increased T-cell activation (IL-2, TNF-α, IFN-γ) were upregulated after miR-149-3p mimic treatment. Moreover, the treatment with a miR-149-3p mimic promoted the capacity of CD8
+
T cells to kill targeted 4T1 mouse breast tumour cells. Collectively, these data show that miR-149-3p can reverse CD8
+
T-cell exhaustion and reveal it to be a potential antitumour immunotherapeutic agent in breast cancer.
Plasma-assisted CO
2
methanation: effects on the low-temperature activity of an Ni–Ce catalyst and reaction performance
Authors: Ge Yuanzheng , He Tao , Han Dezhi , Li Guihua , Zhao Ruidong , Wu Jinhu
Published: October 2019

Ni–Ce three-dimensional material with macropore diameter of 146.6 ± 8.4 nm was synthesized and used as a methanation catalyst. Firstly, H
2
reduction of the catalyst was conducted in the thermal fixed bed and plasma reactor, respectively, then X-ray diffraction (XRD) and CO
2
temperature programmed desorption experiments on the two reduced samples were carried out to reveal the plasma effect on the catalyst's physico-chemical properties. It was found that plasma reduction created more abundant basic sites for CO
2
adsorption, in particular the medium basic sites were even doubled compared with the thermal-reduced catalysts. The plasma-reduced catalyst exhibited excellent low-temperature activity,
ca
50–60°C lower than the thermal catalyst (the maximum CO
2
conversion point). Based on the optimum reduced catalyst, plasma effect in the reactor level was further investigated under high gas hour space velocity of approximately 50 000 h
−1
. The plasma reactor showed higher CO
2
conversion capacity and efficiency than the thermal reactor.
GuUGT, a glycosyltransferase from
Glycyrrhiza uralensis
, exhibits glycyrrhetinic acid 3- and 30-O-glycosylation
Authors: Huang Ying , Li Da , Wang Jinhe , Cai Yi , Dai Zhubo , Jiang Dan , Liu Chunsheng
Published: October 2019

Glycyrrhiza uralensis
is a well-known herbal medicine that contains triterpenoid saponins as the predominant bioactive components, and these compounds include glycyrrhetinic acid (GA)-glycoside derivatives. Although two genes encoding UDP-glycosyltransferases (UGTs) that glycosylate these derivates have been functionally characterized in
G. uralensis
, the mechanisms of glycosylation by other UGTs remain unknown. Based on the available transcriptome data, we isolated a UGT with expression in the roots of
G. uralensis
. This UGT gene possibly encodes a glucosyltransferase that glycosylates GA derivatives at the 3-OH site. Biochemical analyses revealed that the recombinant UGT enzyme could transfer a glucosyl moiety to the free 3-OH or 30-COOH groups of GA. Furthermore, engineered yeast harbouring genes involved in the biosynthetic pathway for GA-glycoside derivates produced GA-3-
O
-β-D-glucoside, implying that the enzyme has GA 3-O-glucosyltransferase activity
in vivo
. Our results could provide a frame for understand the function of the UGT gene family, and also is important for further studies of triterpenoids biosynthesis in
G. uralensis
.
The effect of molecular assembly between collectors and inhibitors on the flotation of pyrite and talc
Authors: Long Tao , Xiao Wei , Yang Wei
Published: October 2019

In the flotation process, the traditional dosing sequence is to add an inhibitor first, followed by a collector. However, in the sorting process of copper sulfide ore, this method of dosing does not effectively separate sulfide minerals and layered magnesium silicate minerals. In this study, the effect of adding a guar gum (as an inhibitor) and potassium amyl xanthate (as a collector, shortened as PAX) sequence to the flotation separation of pyrite and talc was investigated by micro-flotation tests, adsorption amount measurements, contact angle measurement and FT-IR analysis. The results show that the collector only adsorbs on the pyrite surface, while the inhibitor has a strong adsorption capacity on the pyrite and talc surface. Through the change of the order of the flotation reagent addition, PAX preferentially adsorbs on the pyrite surface, thereby preventing guar gum from adsorbing on the pyrite surface and achieving the selective inhibition of talc by guar gum. This study will help in understanding the molecular assembly between collectors and inhibitors to further treat complex copper sulfide nickel ore.
Evolutionary simulations ofZ-linked suppression gene drives
Authors: Holman Luke
Published: October 2019

Synthetic gene drives may soon be used to suppress or eliminate populations of disease vectors, pathogens, invasive species, and agricultural pests. Recent proposals have focused on usingZ-linked gene drives to control species withZWsex determination, which include Lepidopteran pests, parasitic trematodes, and cane toads. These proposals includeZ-linked ‘W-shredders’, which would suppress populations by cleaving theWchromosome and causing females to produce only sons, as well asZ-linked female-sterilizing gene drives. Here, I use eco-evolutionary simulations to evaluate the potential of some proposedZ-linked gene drives, and to produce recommendations regarding their design and use. The simulations show thatW-shredders are likely to be highly effective at eradicating populations provided that resistance toW-shredding cannot evolve. However,W-shredder alleles can invade populations from very low frequencies, making it difficult to eliminate specific populations while leaving nearby populations untouched; this issue may restrict their possible uses.
Parallel genomic architecture underlies repeated sexual signal divergence in HawaiianLaupalacrickets
Authors: Blankers Thomas , Oh Kevin P. , Shaw Kerry L.
Published: October 2019

When the same phenotype evolves repeatedly, we can explore the predictability of genetic changes underlying phenotypic evolution. Theory suggests that genetic parallelism is less likely when phenotypic changes are governed by many small-effect loci compared to few of major effect, because different combinations of genetic changes can result in the same quantitative outcome. However, some genetic trajectories might be favoured over others, making a shared genetic basis to repeated polygenic evolution more likely. To examine this, we studied the genetics of parallel male mating song evolution in the Hawaiian cricketLaupala. We compared quantitative trait loci (QTL) underlying song divergence in three species pairs varying in phenotypic distance. We tested whether replicated song divergence between species involves the same QTL and whether the likelihood of QTL sharing is related to QTL effect size. Contrary to theoretical predictions, we find substantial parallelism in polygenic genetic architectures underlying repeated song divergence. QTL overlapped more frequently than expected based on simulated QTL analyses. Interestingly, QTL effect size did not predict QTL sharing, but did correlate with magnitude of phenotypic divergence. We highlight potential mechanisms driving these constraints on cricket song evolution and discuss a scenario that consolidates empirical quantitative genetic observations with micro-mutational theory.
Phylodynamics reveals extinction–recolonization dynamics underpin apparently endemic vampire bat rabies in Costa Rica
Authors: Streicker Daniel G. , Fallas González Silvia Lucia , Luconi Giovanna , Barrientos Rocío González , Leon Bernal
Published: October 2019

Variation in disease incidence in wildlife is often assumed to reflect environmental or demographic changes acting on an endemic pathogen. However, apparent endemicity might instead arise from spatial processes that are challenging to identify from traditional data sources including time series and field studies. Here, we analysed longitudinal sequence data collected from rabies virus outbreaks over 14 years in Costa Rica, a Central American country that has recorded continuous vampire bat-transmitted rabies outbreaks in humans and livestock since 1985. We identified five phylogenetically distinct lineages which shared most recent common ancestors with viruses from North and South America. Bayesian phylogeographic reconstructions supported bidirectional viral dispersals involving countries to the north and south of Costa Rica at different time points. Within Costa Rica, viruses showed little contemporaneous spatial overlap and no lineage was detected across all years of surveillance. Statistical models suggested that lineage disappearances were more likely to be explained by viral extinctions than undetected viral circulation. Our results highlight the importance of international viral dispersal for shaping the burden of rabies in Costa Rica, suggest a Central American corridor of rabies virus invasions between continents, and show that apparent disease endemicity may arise through recurrent pathogen extinctions and reinvasions which can be readily detected in relatively small datasets by joining phylodynamic and modelling approaches.
Space and rank: infants expect agents in higher position to be socially dominant
Authors: Meng Xianwei , Nakawake Yo , Nitta Hiroshi , Hashiya Kazuhide , Moriguchi Yusuke
Published: October 2019

Social hierarchies exist throughout the animal kingdom, including among humans. Our daily interactions inevitably reflect social dominance relationships between individuals. How do we mentally represent such concepts? Studies show that social dominance is represented as vertical space (i.e. high = dominant) by adults and preschool children, suggesting a space-dominance representational link in social cognition. However, little is known about its early development. Here, we present experimental evidence that 12- to 16-month-old infants expect agents presented in a higher spatial position to be more socially dominant than agents in a lower spatial position. After infants repeatedly watched the higher and lower agents being presented simultaneously, they looked longer at the screen when the lower agent subsequently outcompeted the higher agent in securing a reward object, suggesting that this outcome violated their higher-is-dominant expectation. We first manipulated agents' positions by presenting them on a podium (experiment 1). Then we presented the agents on a double-decker stand to make their spatial positions directly above or below each other (experiment 2), and we replicated the results (experiment 3). This research demonstrates that infants expect spatially higher-positioned agents to be socially dominant, suggesting deep roots of the space-dominance link in ontogeny.
Increases and decreases in marine disease reports in an era of global change
Authors: Tracy Allison M. , Pielmeier Madeline L. , Yoshioka Reyn M. , Heron Scott F. , Harvell C. Drew
Published: October 2019

Outbreaks of marine infectious diseases have caused widespread mass mortalities, but the lack of baseline data has precluded evaluating whether disease is increasing or decreasing in the ocean. We use an established literature proxy method from Ward and Lafferty (Ward and Lafferty 2004
PLoS Biology
2
, e120 (
doi:10.1371/journal.pbio.0020120
)) to analyse a 44-year global record of normalized disease reports from 1970 to 2013. Major marine hosts are combined into nine taxonomic groups, from seagrasses to marine mammals, to assess disease swings, defined as positive or negative multi-decadal shifts in disease reports across related hosts. Normalized disease reports increased significantly between 1970 and 2013 in corals and urchins, indicating positive disease swings in these environmentally sensitive ectotherms. Coral disease reports in the Caribbean correlated with increasing temperature anomalies, supporting the hypothesis that warming oceans drive infectious coral diseases. Meanwhile, disease risk may also decrease in a changing ocean. Disease reports decreased significantly in fishes and elasmobranchs, which have experienced steep human-induced population declines and diminishing population density that, while concerning, may reduce disease. The increases and decreases in disease reports across the 44-year record transcend short-term fluctuations and regional variation. Our results show that long-term changes in disease reports coincide with recent decades of widespread environmental change in the ocean.
The way wear goes: phytolith-based wear on the dentine–enamel system in guinea pigs (Cavia porcellus)
Authors: Martin Louise F. , Winkler Daniela , Tütken Thomas , Codron Daryl , De Cuyper Annelies , Hatt Jean-Michel , Clauss Marcus
Published: October 2019

The effect of phytoliths on tooth wear and function has been contested in studies of animal–plant interactions. For herbivores whose occlusal chewing surface consists of enamel ridges and dentine tissue, the phytoliths might particularly erode the softer dentine, exposing the enamel ridges to different occlusal forces and thus contributing to enamel wear. To test this hypothesis, we fed guinea pigs (Cavia porcellus;n= 36 in six groups) for three weeks exclusively on dry or fresh forage of low (lucerne), moderate (fresh timothy grass) or very high (bamboo leaves) silica content representing corresponding levels of phytoliths. We quantified the effect of these treatments with measurements from micro-computed tomography scans. Tooth height indicated extreme wear due to the bamboo diet that apparently brought maxillary incisors and molars close to the minimum required for functionality. There were negative relationships between a cheek tooth's height and the depth of its dentine basin, corroborating the hypothesis that dentine erosion plays an important role in herbivore tooth wear. In spite of lower body mass, bamboo-fed animals paradoxically had longer cheek tooth rows and larger occlusal surfaces. Because ever-growing teeth can only change in shape from the base upwards, this is a strong indication that failure to compensate for wear by dental height-growth additionally triggered general expansive growth of the tooth bases. The results suggest that enamel wear may intensify after enamel has been exposed due to a faster wear of the surrounding dentine tissue (and not the other way around), and illustrate a surprising plasticity in the reactivity of this rodent's system that adjusts tooth growth to wear.
Critical role of de novo LTD in the formation and maintenance of hippocampal CA1 place-cell fields
Authors: Ashby Donovan M , Seamans Jeremy K , Wang Yu Tian
Published: October 2019

Synaptic plasticity mechanisms may help shape hippocampal place field representations of novel environments, yet direct evidence for how this occurs is lacking. Using multi-channel recordings in freely moving rats, we demonstrate that novelty exploration results in widespread de novo long-term depression (LTD) at hippocampal CA1 synapses in a pathway-specific manner, while blockade of LTD expression impairs the maintenance of newly formed place fields. This study therefore reveals an unrecognized role for LTD in the formation and maintenance of hippocampal place fields in novel environments.
miR-206 family is important for mitochondrial and muscle function, but not essential for myogenesis in vitro
Authors: Przanowska Roza K. , Sobierajska Ewelina , Su Zhangli , Jensen Kate , Przanowski Piotr , Nagdas Sarbajeet , Kashatus Jennifer A. , Kashatus David F. , Bhatnagar Sanchita , Lukens John R. , Dutta Anindya
Published: October 2019

miR-206, miR-1a-1 and miR-1a-2 are induced during differentiation of skeletal myoblasts and promote myogenesis in vitro. miR-206 is required for skeletal muscle regeneration in vivo. Although this microRNA family is hypothesized to play an essential role in differentiation, a triple knockout of the three genes has not been done to test this hypothesis. We report that triple KO C2C12 myoblasts generated using CRISPR/Cas9 method differentiate despite the expected de-repression of the microRNA targets. Surprisingly, their mitochondrial function is diminished. Triple KO mice demonstrate partial embryonic lethality, most likely due to the role of miR-1a in cardiac muscle differentiation. Two triple KO mice survive and grow normally to adulthood with smaller myofiber diameter and diminished physical performance. Thus, unlike other microRNAs important in other differentiation pathways, the miR-206 family is not absolutely essential for myogenesis and is instead a modulator of optimal differentiation of skeletal myoblasts.
Multivariate pattern analysis techniques for electroencephalography data to study interference effects
Authors: López-García David , Sobrado Alberto , Peñalver José M. G. , Górriz Juan Manuel , Ruz María
Published: October 2019

A central challenge in cognitive neuroscience is to understand the neural mechanisms that underlie the capacity to control our behavior according to internal goals. Flanker tasks, which require responding to stimuli surrounded by distracters that trigger incompatible action tendencies, are frequently used to measure this conflict. Even though the interference generated in these situations has been broadly studied, multivariate analysis techniques can shed new light into the underlying neural mechanisms. The current study is an initial approximation to adapt an interference Flanker paradigm embedded in a Demand-Selection Task to a format that allows measuring concurrent high-density electroencephalography. We used multivariate pattern analysis (MVPA) to decode conflictrelated neural processes associated with congruent or incongruent target events in a time-frequency resolved way. Our results replicate findings obtained with other analysis approaches and offer new information regarding the dynamics of the underlying mechanisms, which show signs of reinstantiation. Our findings, some of which could not had been obtained with classic analytical strategies, open novel avenues of research.
Phase separation by ssDNA binding protein controlledviaprotein-protein and protein-DNA interactions
Authors: Harami Gábor M. , Kovács Zoltán J. , Pancsa Rita , Pálinkás János , Baráth Veronika , Tárnok Krisztián , Málnási-Csizmadia András , Kovács Mihály
Published: October 2019

Bacterial single stranded (ss) DNA-binding proteins (SSB) are essential for the replication and maintenance of the genome. SSBs share a conserved ssDNA-binding domain, a less conserved intrinsically disordered linker (IDL) and a highly conserved C-terminal peptide (CTP) motif that mediates a wide array of protein-protein interactions with DNA-metabolizing proteins. Here we show that theE. coliSSB protein forms liquid-liquid phase separated condensates in cellular-like conditions through multifaceted interactions involving all structural regions of the protein. SSB, ssDNA and SSB-interacting molecules are highly concentrated within the condensates, whereas phase separation is overall regulated by the stoichiometry of SSB and ssDNA. Together with recent results on subcellular SSB localization patterns, our results point to a conserved mechanism by which bacterial cells store a pool of SSB and SSB-interacting proteins. Dynamic phase separation enables rapid mobilization of this protein pool to protect exposed ssDNA and repair genomic loci affected by DNA damage.
Automated cryo-lamella preparation for high-throughput in-situ structural biology
Authors: Buckley Genevieve , Gervinskas Gediminas , Taveneau Cyntia , Venugopal Hari , Whisstock James C. , de Marco Alex
Published: October 2019

Cryo-transmission electron tomography (cryo-ET) in association with cryo-focused ion beam (cryo-FIB) milling enables structural biology studies to be performed directly within the cellular environment. Cryo-preserved cells are milled and a lamella with a thickness of 200-300 nm provides an electron transparent window suitable for cryo-ET imaging. Cryo-FIB milling is an effective method, but it is a tedious and time-consuming process, which typically results in ~10 lamellae per day. Here, we introduce an automated method to reproducibly prepare cryo-lamellae on a grid and reduce the amount of human supervision. We tested the routine on cryo-preserved Saccharomyces cerevisiae and demonstrate that this method allows an increased throughput, achieving a rate of 5 lamellae/hour without the need to supervise the FIB milling. We demonstrate that the quality of the lamellae is consistent throughout the preparation and their compatibility with cryo-ET analyses.
Fully automated, sequential focused ion beam milling for cryo-electron tomography
Authors: Zachs Tobias , Medeiros João M. , Schertel Andreas , Weiss Gregor L. , Hugener Jannik , Pilhofer Martin
Published: October 2019

Cryo-electron tomography (cryoET) has become a powerful technique at the interface of structural biology and cell biology, with the unique ability to determine structures of macromolecular complexes in their cellular context. A major limitation of cryoET is its restriction to relatively thin samples. Sample thinning by cryo-focused ion beam (cryoFIB) milling has significantly expanded the range of samples that can be analyzed by cryoET. Unfortunately, cryoFIB milling is low-throughput, time-consuming and manual. Here we report a method for fully automated sequential cryoFIB preparation of high-quality lamellae, including rough milling and polishing. We reproducibly applied this method to eukaryotic and bacterial model organisms, and show that the resulting lamellae are suitable for cryoET imaging and subtomogram averaging. Since our method reduces the time required for lamella preparation and minimizes the need for user input, we envision the technique will render previously inaccessible projects feasible.
Somatic selection of poorly differentiating variant stem cell clones could be a key to human ageing
Authors: Bodmer Walter F. , Crouch Daniel J. M.
Published: October 2019

Any replicating system in which heritable variants with differing replicative potentials can arise is subject to a Darwinian evolutionary process. The continually replicating adult tissue stem cells that control the integrity of many tissues of long-lived, multicellular, complex vertebrate organisms, including humans, constitute such a replicating system. Our suggestion is that somatic selection for mutations (or stable epigenetic changes) that cause an increased rate of adult tissue stem cell proliferation, and their long-term persistence, at the expense of normal differentiation, is a major key to the ageing process. Once an organism has passed the reproductive age, there is no longer any significant counterselection at the organismal level to this inevitable cellular level Darwinian process.

Author Contributions

WFB conceived the project. WFB and DJMC wrote the manuscript.
Human CST complex protects replication fork stability by directly blocking MRE11 degradation of nascent strand DNA
Authors: Lyu Xinxing , Lei Kai-Hang , Shiva Olga , Chastain Megan , Chi Peter , Chai Weihang
Published: October 2019

Degradation and collapse of stalled replication forks are main sources of genome instability, yet the molecular mechanism for protecting forks from degradation/collapse is not well understood. Here, we report that human CST (CTC1-STN1-TEN1), a single-stranded DNA binding protein complex, localizes at stalled forks and protects forks from MRE11 nuclease degradation upon replication perturbation. CST deficiency causes nascent strand degradation, ssDNA accumulation after fork stalling, and delay in replication recovery, leading to cellular sensitivity to fork stalling agents. Purified CST binds to 5’ overhangs and directly blocks MRE11 degradation in vitro, and the DNA binding ability of CST is required for blocking MRE11-mediated nascent strand degradation. Finally, we uncover that CST and BRCA2 form non-overlapping foci upon fork stalling, and CST inactivation is synthetic with BRCA2 deficiency in inducing genome instability. Collectively, our findings identify CST as an important fork protector to preserve genome integrity under replication perturbation.
Insects as phyllosphere microbiome engineers: effects of aphids on a plant pathogen
Authors: Smee Melanie R. , Real-Ramirez Imperio , Hendry Tory A.
Published: October 2019

Insect herbivores are common in the phyllosphere, the above-ground parts of plants, and encounter diverse plant-associated bacteria there, yet how these organisms interact remains largely unknown. Strains of the bacteriumPseudomonas syringaegrow well epiphytically and have been shown to grow within and kill hemipteran insects like the pea aphid,Acyrthosiphon pisum. Aphids are hypothesized to be an alternative host for these epiphytic bacteria but it is unclear if aphids provide fitness benefits to these bacterial pathogens. To determine if epiphytic bacteria could be adapted for infecting aphids, we characterized 21 strains ofP. syringaefor epiphytic ability and virulence to pea aphids and found that the two traits were positively correlated. For a subset of strains, we tested if the bacteria derived a fitness benefit from the presence of aphids. Some strains benefited significantly, with up to 18.9% higher population densities when aphids were present, and lower starting population density was predictive of higher benefit from aphid presence. However, further investigation found that honeydew, the sugary waste product of aphids, and not growth in aphids, increasedP. syringaegrowth on leaves. This suggests that aphids may be important microbiome engineers in the phyllosphere, but evolutionarily dead-ends for epiphytic bacteria.
Usefulness of a familiarity signal during recognition depends on test format: Neurocognitive evidence for a core assumption of the CLS framework
Authors: Bader Regine , Mecklinger Axel , Meyer Patric
Published: October 2019

Familiarity-based discrimination between studied target items and similar foils in yes/no recognition memory tests is relatively poor. According to the complementary learning systems (CLS) framework this is due do a relatively small difference in familiarity strength between these two item classes. The model, however, also predicts that when targets and corresponding similar foils are presented next to each other in a forced-choice corresponding (FCC) test format, familiarity values for targets and foils can be directly compared because in each trial, targets are reliably more familiar than their corresponding foils. In contrast, when forced-choice displays contain non-corresponding foils (FCNC) which are similar to other studied items (but not the target), familiarity should not be diagnostic because familiarity values are not directly comparable (as in yes/no-tasks). We compared ERP old/new effects (ERPs of targets vs. foils) when participants were tested with FCC vs. FCNC displays after having intentionally encoded pictures of objects. As predicted, the mid-frontal old/new effect which is associated with familiarity was significantly larger in FCC compared to FCNC displays. Moreover, the target-foil amplitude difference predicted the accuracy of the recognition judgment in a given trial. This is one of the very few studies which support the assumption of the CLS framework that the test format can influence the diagnosticity of familiarity. Moreover, it implies that the mid-frontal old/new effect does not reflect the mean difference in the familiarity signal itself between studied and non-studied items but reflects the task-adequate assessment of the familiarity signal.
Establishment of chromatin accessibility by the conserved transcription factor Grainy head is developmentally regulated
Authors: Nevil Markus , Gibson Tyler J. , Bartolutti Constantine , Iyengar Anusha , Harrison Melissa M
Published: October 2019

The dramatic changes in gene expression required for development necessitate the establishment ofcis-regulatory modules defined by regions of accessible chromatin. Pioneer transcription factors have the unique property of binding closed chromatin and facilitating the establishment of these accessible regions. Nonetheless, much of how pioneer transcription factors coordinate changes in chromatin accessibility during development remains unknown. To determine whether pioneer-factor function is intrinsic to the protein or whether pioneering activity is developmentally modulated, we studied the highly conserved, essential transcription factor, Grainy head (Grh). Grh is expressed throughoutDrosophiladevelopment and functions as a pioneer factor in the larvae. We demonstrated that Grh remains bound to condensed mitotic chromosomes, a property shared with other pioneer factors. By assaying chromatin accessibility in embryos lacking either maternal or zygotic Grh at three stages of development, we discovered that Grh is not required for chromatin accessibility in early embryogenesis, in contrast to its essential functions later in development. Our data reveal that the pioneering activity of Grh is temporally regulated and is likely influenced by additional factors expressed at a given developmental stage.