bluuebunny/crossref_metadata_2025 huggingface dataset:
A Short Note on Marine Reservoir Age Simulations Used in IntCal20
Authors: Butzin Martin , Heaton Timothy J , Köhler Peter , Lohmann Gerrit
Published: February 2020

Beyond ~13.9 cal kBP, the IntCal20 radiocarbon (14C) calibration curve is based upon combining data across a range of different archives including corals and planktic foraminifera. In order to reliably incorporate such marine data into an atmospheric curve, we need to resolve these records into their constituent atmospheric signal and marine reservoir age. We present results of marine reservoir age simulations enabling this resolution, applying the LSG ocean general circulation model forced with various climatic background conditions and with atmospheric radiocarbon changes according to the Hulu Cave speleothem record. Simulating the spatiotemporal evolution of reservoir ages between 54,000 and 10,700 cal BP, we find reservoir ages between 500 and 1400 yr in the low- and mid-latitudes, but also more than 3000 yr in the polar seas. Our results are broadly in agreement with available marine radiocarbon reconstructions, with the caveat that continental margins, marginal seas, or tropical lagoons are not properly resolved in our coarse-resolution model.
STRUCTURING THE ‘HISTORY OF PHILOSOPHY’—A COMPARISON BETWEEN PHILODEMUS AND DIOGENES LAERTIUS IN THE LIGHT OF NEW EVIDENCE
Authors: Fleischer Kilian
Published: February 2020

Considering the fair amount of ancient authors who compiled works on the subject of the ‘History of Philosophy’, it is remarkable—and regrettable—that there is no solid basis for a comparative analysis of their structures. Most ancient histories of philosophy are only preserved in a few fragments or excerpts and hardly allow any meaningful non-trivial comparison of the structure and order of the philosophers and schools discussed. The only more or less entirely preserved ‘History of Philosophy’ is Diogenes Laertius’ famous treatise. Although his work seems to offer an idiosyncratic rendering in some respects, and is hardly representative of the genre, some structural similarities with Sotion's Διαδοχαί (Successions) can be identified. Generally, a crucial question concerning the structure is how the philosophers and their schools were arranged in these works. Did the works basically follow a chronological order? How were the Διαδοχαί arranged? Were certain schools or philosophers dealt with together in a single book or in more than one book, or were they presented in a certain order?
Complications and predisposing factors from a decade of total laryngectomy
Authors: Thompson C S G , Asimakopoulos P , Evans A , Vernham G , Hay A J , Nixon I J
Published: February 2020

Background

Total laryngectomy is often utilised to manage squamous cell carcinoma of the larynx or hypopharynx. This study reports on surgical trends and outcomes over a 10-year period.

Method

A retrospective review of patients undergoing total laryngectomy for squamous cell carcinoma was performed (n= 173), dividing patients into primary and salvage total laryngectomy cohorts.

Results

A shift towards organ-sparing management was observed. Primary total laryngectomy was performed for locoregionally advanced disease and utilised reconstruction less than salvage total laryngectomy. Overall, 11 per cent of patients developed pharyngocutaneous fistulae (primary: 6 per cent; salvage: 20 per cent) and 11 per cent neopharyngeal stenosis (primary: 9 per cent; salvage: 15 per cent). Pharyngocutaneous fistulae rates were higher in the reconstructed primary total laryngectomy group (24 per cent; 4 of 17), compared with primary closure (3 per cent; 3 of 90) (p =0.02). Patients were significantly more likely to develop neopharyngeal stenosis following pharyngocutaneous fistulae in salvage total laryngectomy (p =0.01) and reconstruction in primary total laryngectomy (p =0.02). Pre-operative haemoglobin level and adjuvant treatment failed to predict pharyngocutaneous fistulae development.

Conclusion

Complications remain hard to predict and there are continuing causes of morbidity. Additionally, prior treatment continues to affect surgical outcomes.
Two closed orbits for non-degenerate Reeb flows
Authors: ABREU MIGUEL , GUTT JEAN , KANG JUNGSOO , MACARINI LEONARDO
Published: February 2020

We prove that every non-degenerate Reeb flow on a closed contact manifold M admitting a strong symplectic filling W with vanishing first Chern class carries at least two geometrically distinct closed orbits provided that the positive equivariant symplectic homology of W satisfies a mild condition. Under further assumptions, we establish the existence of two geometrically distinct closed orbits on any contact finite quotient of M. Several examples of such contact manifolds are provided, like displaceable ones, unit cosphere bundles, prequantisation circle bundles, Brieskorn spheres and toric contact manifolds. We also show that this condition on the equivariant symplectic homology is preserved by boundary connected sums of Liouville domains. As a byproduct of one of our applications, we prove a sort of Lusternik–Fet theorem for Reeb flows on the unit cosphere bundle of not rationally aspherical manifolds satisfying suitable additional assumptions.
Embryonic and early larval development of two marine angelfish, Centropyge bicolor and Centropyge bispinosa
Authors: Mendonça Raoani Cruz , Chen Jun Yu , Zeng Chaoshu , Tsuzuki Mônica Yumi
Published: February 2020

Marine angelfish (family: Pomacanthidae) are among the most sought-after fish species in the saltwater aquarium trade. However, there is a lack of information in the literature on their early ontogeny. The objective of this study was to describe the embryonic and early larval development of two dwarf angelfish, the bicolour angelfish, Centropyge bicolor and the coral beauty angelfish, Centropyge bispinosa. The eggs of these two species were obtained from spontaneous spawning of the broodstock fish in captivity and incubated at 26.0 ± 0.2°C throughout the study. Fertilized eggs (n = 15) of both species are transparent, pelagic and spherical; the mean diameters of the eggs were measured at 703.6 ± 7.8 μm for C. bicolor and 627.6 ± 7.8 μm for C. bispinosa. The eggs of both species possessed a narrow perivitelline space, smooth and thin chorion, a homogenous and non-segmented yolk as well as a single oil globule. Overall, the observed embryonic development pattern of C. bicolor and C. bispinosa was very similar, and the main difference was the embryonic pigmentation pattern, which only became evident close to hatching. Larvae of both species started hatching at 13 h 30 min after fertilization, and the larval characteristics of both species also showed high levels of similarities. However, the mouth opening time for C. bicolor was 72 h after hatching (AH) and 96 AH for C. bispinosa. In general, the observed early ontogeny of C. bicolor and C. bispinosa also resembled that of other Centropyge species documented in the literature.
Acute treatment of critical vascular stenoses with a bioabsorbable magnesium scaffold in infants with CHDs
Authors: Zartner Peter A. , Schranz Dietmar , Mini Nathalie , Schneider Martin B. , Schneider Katja
Published: February 2020

Background:

Post-operative severe vascular stenosis and proliferating endothelial tissue lead to severe circulatory disorders and impair organ perfusion. Bioabsorbable magnesium scaffolds may help to overcome these obstructions without leaving obstructing stent material. We analyse their role in the treatment of vascular stenosis in infants.

Methods:

Since 2016, 15 magnesium scaffolds with a diameter of 3.5 mm were implanted in 9 patients aged 15 days to 7.6 years. Eight scaffolds were implanted in pulmonary venous restenoses, five in pulmonary arterial stenosis including one in-stent stenosis, one into a stenotic brachiocephalic artery, and one in a recurrent innominate vein thrombosis.

Results:

All patients clinically improved after the implantation of a scaffold. The magnesium scaffolds lost integrity after 30–48 days (mean 42 days). The innominate vein thrombosed early, while all other vessels remained open. Two patients died after 1.3 and 14 weeks not related to the scaffolds. Five patients needed further balloon dilations or stent implantations after the scaffold had fractured. At first recatheterisation after in mean 2.5 months, the mean minimum/maximum diameter in relation to the scaffold’s original diameter was 89%/99% in the arterial implantations (n = 6) and 66%/77% in the pulmonary venous implantations.

Conclusions:

The magnesium scaffolds can be used as a bridging solution to treat severe vascular stenosis in different locations. Restenosis can occur after degradation and make further interventions necessary, but neither vessel growth nor further interventions are hindered by stent material. Larger diameters may improve therapeutic options.
Efficacy of bacterial vaccines to prevent respiratory disease in swine: a systematic review and network meta-analysis
Authors: Sargeant Jan M. , Deb Bhumika , Bergevin Michele D. , Churchill Katheryn , Dawkins Kaitlyn , Dunn Jennifer , Hu Dapeng , Moody Carly , O'Connor Annette M. , O'Sullivan Terri L. , Reist Mark , Wang Chong , Wilhelm Barbara , Winder Charlotte B.
Published: February 2020

A systematic review and network meta-analysis (MA) was conducted to address the question, ‘What is the efficacy of bacterial vaccines to prevent respiratory disease in swine?’ Four electronic databases and the grey literature were searched to identify clinical trials in healthy swine where at least one intervention arm was a commercially available vaccine for one or more bacterial pathogens associated with respiratory disease in swine, includingMycoplasma hyopneumoniae,Actinobacillus pleuropneumonia,Actinobacillus suis,Bordetella bronchiseptica,Pasteurella multocida,Stretococcus suis,Haemophils parasuis, andMycoplasma hyorhinis. To be eligible, trials had to measure at least one of the following outcomes: incidence of clinical morbidity, mortality, lung lesions, or total antibiotic use. There were 179 eligible trials identified in 146 publications. Network MA was undertaken for morbidity, mortality, and the presence or absence of non-specific lung lesions. However, there was not a sufficient body of research evaluating the same interventions and outcomes to allow a meaningful synthesis of the comparative efficacy of the vaccines. To build this body of research, additional rigor in trial design and analysis, and detailed reporting of trial methods and results are warranted.
A systematic review of the efficacy of antibiotics for the prevention of swine respiratory disease
Authors: Sargeant Jan M. , Bergevin Michele D. , Churchill Katheryn , Dawkins Kaitlyn , Deb Bhumika , Dunn Jennifer , Hu Dapeng , Moody Carly , O'Connor Annette M. , O'Sullivan Terri L. , Reist Mark , Wang Chong , Wilhelm Barbara , Winder Charlotte B.
Published: February 2020

Prevention and control of respiratory disease is a major contributor to antibiotic use in swine. A systematic review was conducted to address the question, ‘What is the comparative efficacy of antimicrobials for the prevention of swine respiratory disease?’ Eligible studies were controlled trials published in English evaluating prophylactic antibiotics in swine, where clinical morbidity, mortality, or total antibiotic use was assessed. Four databases and the gray literature were searched for relevant articles. Two reviewers working independently screened titles and abstracts for eligibility followed by full-text articles, and then extracted data and evaluated risk of bias for eligible trials. There were 44 eligible trials from 36 publications. Clinical morbidity was evaluated in eight trials where antibiotics were used in nursery pigs and 10 trials where antibiotics were used in grower pigs. Mortality was measured in 22 trials in nursery pigs and 12 trials in grower pigs. There was heterogeneity in the antibiotic interventions and comparisons published in the literature; thus, there was insufficient evidence to allow quantification of the efficacy, or relative efficacy, of antibiotic interventions. Concerns related to statistical non-independence and quality of reporting were noted in the included trials.
Systematic reviews and meta-analyses in animal health, performance, and on-farm food safety: a scoping review
Authors: Vriezen Rachael , Sargeant Jan M. , Vriezen Ellen , Reist Mark , Winder Charlotte B. , O'Connor Annette M.
Published: February 2020

Systematic reviews and meta-analyses are used to summarize and interpret evidence for clinical decision-making in human health. The extent of the application of these methods in veterinary medicine and animal agriculture is unknown. The goal of this scoping study was to ascertain trends in the publication of systematic reviews and meta-analyses examining animal health, animal performance, and on-farm food safety. Online databases were searched for reviews published between 1993 and 2018 that focused on relevant outcomes in domestic livestock, companion animals, or wildlife species. In total 1787 titles and abstracts underwent data characterization. Dairy cattle, fish, and pigs were the most common target commodity groups. Few articles investigated both health and performance outcomes (only health:n= 418; only performance:n= 701; both health and performance:n= 103). Most of the reviews (67.6%,n= 1208/1787) described a meta-analysis but did not state in the title or abstract that a systematic review was also conducted, which is potentially problematic. Adherence to reporting guidelines is recommended for all systematic reviews and meta-analyses. For research areas with many reviews, an evidence repository is recommended. For less well-reviewed areas, additional investigation may be necessary to identify the reasons for the lack of synthesis research.
Editorial: Systematic reviews reveal a need for more, better data to inform antimicrobial stewardship practices in animal agriculture
Authors: Sargeant Jan M. , O'Connor Annette M. , Winder Charlotte B.
Published: February 2020

This editorial summarizes the key observations from a special issue ofAnimal Health Research Reviewscomprising 14 articles related to the efficacy of antimicrobial and non-antimicrobial approaches to reduce disease in beef, dairy cattle, swine, and broiler chickens. The articles used evidence-based methods, including scoping reviews, systematic reviews, meta-analyses, and network meta-analyses. Despite finding evidence of efficacy for some of the interventions examined, across the body of research, there was a lack of replication and inconsistency in outcomes among the included trials, and concerns related to completeness of reporting and trial design and execution. There is an urgent need for more and better data to inform antimicrobial stewardship practices in animal agriculture.
The Policy on Children of the ICC Office of the Prosecutor: Toward greater accountability for crimes against and affecting children
Authors: Amann Diane Marie
Published: February 2020

The Policy on Children published by the International Criminal Court (ICC) Office of the Prosecutor in 2016 represents a significant step toward accountability for harms to children in armed conflict and similar situations of extreme violence. This article describes the process that led to the Policy and outlines the Policy's contents. It then surveys relevant ICC practice and related developments, concluding that despite some salutary efforts, much remains to be done to recognize, prevent and punish the spectrum of conflicted-related crimes against or affecting children.
Localized Heating of the Martian Topside Ionosphere Through the Combined Effects of Magnetic Pumping by Large‐Scale Magnetosonic Waves and Pitch Angle Diffusion by Whistler Waves
Authors: Fowler C. M. , Agapitov O. V. , Xu S. , Mitchell D. L. , Andersson L. , Artemyev A. , Espley J. , Ergun R. E. , Mazelle C.
Published: February 2020

We present Mars Atmosphere and Volatile EvolutioN (MAVEN) observations of periodic (
25 s) large‐scale (hundreds of km) magnetosonic waves propagating into the Martian dayside upper ionosphere. These waves adiabatically modulate the superthermal electron distribution function, and the induced electron temperature anisotropies drive the generation of observed electromagnetic whistler waves. The localized (in altitude) minimum in the ratio
pe/
ce provides conditions favorable for the local enhancement of efficient wave‐particle interactions, so that the induced whistlers act back on the superthermal electron population to isotropize the plasma through pitch angle scattering. These wave‐particle interactions break the adiabaticity of the large‐scale magnetosonic wave compressions, leading to local heating of the superthermal electrons during compressive wave “troughs.” Further evidence of this heating is observed as the subsequent phase shift between the observed perpendicular‐to‐parallel superthermal electron temperatures and compressive wave fronts. This heating mechanism may be important at other unmagnetized bodies.
Evidence for Multiple Superposed Fluvial Deposits Within Reuyl Crater, Mars
Authors: Vijayan S. , Sinha Rishitosh K. , Harish  , Anilkumar Ritu
Published: February 2020

Reuyl is an 85‐km‐diameter crater located east of the Aeolis Dorsa region. We present results from geomorphic mapping and high‐resolution image analyses of Reuyl to understand the provenance of alluvial fans, superposed deposits, channels, and sinuous ridges. We distinguish 29 fans or other deposits associated with channels based on their characteristics. Two sinuous ridges are associated with the alluvial fans formed between the wall and peak region. On the southern floor, a sinuous ridge associated with an alluvial fan with channel inversion is orthogonally superposed by another wall‐originated fan deposit. On the western floor, a sinuous ridge associated with an alluvial fan is superposed by wall‐originated deposits. We also observe bajadas, stacked deposits, deposits with incised channels, and overlapping fan ridges, which suggest diverse and long‐lived depositional activity related to a fluvial environment. The central peak is surrounded by a mound deposit with several discontinuous channels. One large fan from the western wall appears more intact than the others, being less eroded and lacking ridges. Reuyl aged as ~3.63 Ga, whereas the first‐order analysis of the fan deposits implies ~3.5 Ga and the large intact deposit is estimated to belong to the Amazonian epoch. We suggest that Reuyl crater likely witnessed and recorded the transition from alluvial fan to large younger intact deposits, which possibly suggests a decrease in water/volatile‐related activity and/or change in sediment supply. Overall, the diverse superposed fan deposits within Reuyl reveal noncoeval activity and provide comprehensive evidence for long‐lived fluvial activity during the post‐Noachian epoch.
Subsurface Radiation Environment of Mars and Its Implication for Shielding Protection of Future Habitats
Authors: Röstel Lennart , Guo Jingnan , Banjac Saša , Wimmer‐Schweingruber Robert F. , Heber Bernd
Published: February 2020

In order to quantify the optimal radiation shielding depth on Mars in preparation for future human habitats on the red planet, it is important to understand the Martian radiation environment and its dependence on the planetary atmospheric and geological properties. With this motivation we calculate the absorbed dose and equivalent dose rates induced by galactic cosmic ray particles at varying heights above and below the Martian surface considering various subsurface compositions (ranging from dry rock to water‐rich regolith). The state‐of‐the‐art Atmospheric Radiation Interaction Simulator based on GEometry And Tracking Monte Carlo method has been employed for simulating particle interaction with the Martian atmosphere as well as subsurface materials. We calculate the absorbed dose in two different phantoms: a thin silicon slab and a water sphere. The former is used to validate our model against the surface measurement by the Radiation Assessment Detector on the Curiosity rover, while the later is used to approximate a human torso, also for evaluation of the biologically weighted equivalent dose. We find that the amount of hydrogen contained in the water‐rich regolith plays an important role in reducing the equivalent dose through modulation of neutron flux (below 10 MeV). This effective shielding by underground water is also present above the surface, providing an indirect shielding for potential human explorations at this region. For long‐term habitats seeking the Martian natural surface material as protection, we also estimate the optimal shielding depth, for different given subsurface compositions, under maximum, average, and minimum heliospheric modulation conditions.
Chemically resistant and thermally stable quantum dots prepared by shell encapsulation with cross-linkable block copolymer ligands
Authors: Ko Jaewan , Jeong Byeong Guk , Chang Jun Hyuk , Joung Joonyoung F. , Yoon Suk-Young , Lee Doh C. , Park Sungnam , Huh June , Yang Heesun , Bae Wan Ki , Jang Se Gyu , Bang Joona
Published: February 2020

Endowing quantum dots (QDs) with robustness and durability have been one of the most important issues in this field, since the major limitations of QDs in practical applications are their thermal and oxidative instabilities. In this work, we propose a facile and effective passivation method to enhance the photochemical stability of QDs using polymeric double shell structures from thiol-terminated poly(methyl methacrylate-b-glycidyl methacrylate) (P(MMA-b-GMA)-SH) block copolymer ligands. To generate a densely cross-linked network, the cross-linking reaction of GMA epoxides in the PGMA block was conducted using a Lewis acid catalyst under an ambient environment to avoid affecting the photophysical properties of the pristine QDs. This provides QDs encapsulated with robust double layers consisting of highly transparent PMMA outer-shell and oxidation-protective cross-linked inner shell. Consequently, the resulting QDs exhibited exceptional tolerance to heat and oxidants when dispersed in organic solvents or QD-nanocomposite films, as demonstrated under various harsh conditions with respect to temperature and oxidant species. The present approach not only provides simple yet effective chemical means to enhance the thermochemical stability of QDs, but also offers a promising platform for the hybridization of QDs with polymeric materials for developing robust light-emitting or light-harvesting devices.
Exploiting horizontal pleiotropy to search for causal pathways within a Mendelian randomization framework
Authors: Cho Yoonsu , Haycock Philip C. , Sanderson Eleanor , Gaunt Tom R. , Zheng Jie , Morris Andrew P. , Davey Smith George , Hemani Gibran
Published: February 2020

In Mendelian randomization (MR) analysis, variants that exert horizontal pleiotropy are typically treated as a nuisance. However, they could be valuable in identifying alternative pathways to the traits under investigation. Here, we develop MR-TRYX, a framework that exploits horizontal pleiotropy to discover putative risk factors for disease. We begin by detecting outliers in a single exposure–outcome MR analysis, hypothesising they are due to horizontal pleiotropy. We search across hundreds of complete GWAS summary datasets to systematically identify other (candidate) traits that associate with the outliers. We develop a multi-trait pleiotropy model of the heterogeneity in the exposure–outcome analysis due to pathways through candidate traits. Through detailed investigation of several causal relationships, many pleiotropic pathways are uncovered with already established causal effects, validating the approach, but also alternative putative causal pathways. Adjustment for pleiotropic pathways reduces the heterogeneity across the analyses.
Klf5 acetylation regulates luminal differentiation of basal progenitors in prostate development and regeneration
Authors: Zhang Baotong , Ci Xinpei , Tao Ran , Ni Jianping Jenny , Xuan Xiaoyan , King Jamie L. , Xia Siyuan , Li Yixiang , Frierson Henry F. , Lee Dong-Kee , Xu Jianming , Osunkoya Adeboye O. , Dong Jin-Tang
Published: February 2020

Prostate development depends on balanced cell proliferation and differentiation, and acetylated KLF5 is known to alter epithelial proliferation. It remains elusive whether post-translational modifications of transcription factors can differentially determine adult stem/progenitor cell fate. Here we report that, in human and mouse prostates, Klf5 is expressed in both basal and luminal cells, with basal cells preferentially expressing acetylated Klf5. Functionally, Klf5 is indispensable for maintaining basal progenitors, their luminal differentiation, and the proliferation of their basal and luminal progenies. Acetylated Klf5 is also essential for basal progenitors’ maintenance and proper luminal differentiation, as deacetylation of Klf5 causes excess basal-to-luminal differentiation; attenuates androgen-mediated organoid organization; and retards postnatal prostate development. In basal progenitor-derived luminal cells, Klf5 deacetylation increases their proliferation and attenuates their survival and regeneration following castration and subsequent androgen restoration. Mechanistically, Klf5 deacetylation activates Notch signaling. Klf5 and its acetylation thus contribute to postnatal prostate development and regeneration by controlling basal progenitor cell fate.
Serial protein crystallography in an electron microscope
Authors: Bücker Robert , Hogan-Lamarre Pascal , Mehrabi Pedram , Schulz Eike C. , Bultema Lindsey A. , Gevorkov Yaroslav , Brehm Wolfgang , Yefanov Oleksandr , Oberthür Dominik , Kassier Günther H. , Dwayne Miller R. J.
Published: February 2020

Serial X-ray crystallography at free-electron lasers allows to solve biomolecular structures from sub-micron-sized crystals. However, beam time at these facilities is scarce, and involved sample delivery techniques are required. On the other hand, rotation electron diffraction (MicroED) has shown great potential as an alternative means for protein nano-crystallography. Here, we present a method for serial electron diffraction of protein nanocrystals combining the benefits of both approaches. In a scanning transmission electron microscope, crystals randomly dispersed on a sample grid are automatically mapped, and a diffraction pattern at fixed orientation is recorded from each at a high acquisition rate. Dose fractionation ensures minimal radiation damage effects. We demonstrate the method by solving the structure of granulovirus occlusion bodies and lysozyme to resolutions of 1.55 Å and 1.80 Å, respectively. Our method promises to provide rapid structure determination for many classes of materials with minimal sample consumption, using readily available instrumentation.
Nanofabrication for all-soft and high-density electronic devices based on liquid metal
Authors: Kim Min-gu , Brown Devin K. , Brand Oliver
Published: February 2020

Innovations in soft material synthesis and fabrication technologies have led to the development of integrated soft electronic devices. Such soft devices offer opportunities to interact with biological cells, mimicking their soft environment. However, existing fabrication technologies cannot create the submicron-scale, soft transducers needed for healthcare and medical applications involving single cells. This work presents a nanofabrication strategy to create submicron-scale, all-soft electronic devices based on eutectic gallium-indium alloy (EGaIn) using a hybrid method utilizing electron-beam lithography and soft lithography. The hybrid lithography process is applied to a biphasic structure, comprising a metallic adhesion layer coated with EGaIn, to create soft nano/microstructures embedded in elastomeric materials. Submicron-scale EGaIn thin-film patterning with feature sizes as small as 180 nm and 1 μm line spacing was achieved, resulting in the highest resolution EGaIn patterning technique to date. The resulting soft and stretchable EGaIn patterns offer a currently unrivaled combination of resolution, electrical conductivity, and electronic/wiring density.
Optogenetic modulation of TDP-43 oligomerization accelerates ALS-related pathologies in the spinal motor neurons
Authors: Asakawa Kazuhide , Handa Hiroshi , Kawakami Koichi
Published: February 2020

Cytoplasmic aggregation of TDP-43 characterizes degenerating neurons in most cases of amyotrophic lateral sclerosis (ALS). Here, we develop an optogenetic TDP-43 variant (opTDP-43), whose multimerization status can be modulated in vivo through external light illumination. Using the translucent zebrafish neuromuscular system, we demonstrate that short-term light stimulation reversibly induces cytoplasmic opTDP-43 mislocalization, but not aggregation, in the spinal motor neuron, leading to an axon outgrowth defect associated with myofiber denervation. In contrast, opTDP-43 forms pathological aggregates in the cytoplasm after longer-term illumination and seeds non-optogenetic TDP-43 aggregation. Furthermore, we find that an ALS-linked mutation in the intrinsically disordered region (IDR) exacerbates the light-dependent opTDP-43 toxicity on locomotor behavior. Together, our results propose that IDR-mediated TDP-43 oligomerization triggers both acute and long-term pathologies of motor neurons, which may be relevant to the pathogenesis and progression of ALS.
Universal slow plasmons and giant field enhancement in atomically thin quasi-two-dimensional metals
Authors: da Jornada Felipe H. , Xian Lede , Rubio Angel , Louie Steven G.
Published: February 2020

Plasmons depend strongly on dimensionality: while plasmons in three-dimensional systems start with finite energy at wavevector q = 0, plasmons in traditional two-dimensional (2D) electron gas disperse as $$\omega _p \sim \sqrt q$$

ω

p

~

q

. However, besides graphene, plasmons in real, atomically thin quasi-2D materials were heretofore not well understood. Here we show that the plasmons in real quasi-2D metals are qualitatively different, being virtually dispersionless for wavevectors of typical experimental interest. This stems from a broken continuous translational symmetry which leads to interband screening; so, dispersionless plasmons are a universal intrinsic phenomenon in quasi-2D metals. Moreover, our ab initio calculations reveal that plasmons of monolayer metallic transition metal dichalcogenides are tunable, long lived, able to sustain field intensity enhancement exceeding 107, and localizable in real space (within ~20 nm) with little spreading over practical measurement time. This opens the possibility of tracking plasmon wave packets in real time for novel imaging techniques in atomically thin materials.
World Trade Center-Cardiorespiratory and Vascular Dysfunction: Assessing the Phenotype and Metabolome of a Murine Particulate Matter Exposure Model
Authors: Veerappan Arul , Oskuei Assad , Crowley George , Mikhail Mena , Ostrofsky Dean , Gironda Zakia , Vaidyanathan Sandhya , Wadghiri Youssef Zaim , Liu Mengling , Kwon Sophia , Nolan Anna
Published: February 2020

Vascular changes occur early in the development of obstructive airways disease. However, the vascular remodeling and dysfunction due to World Trade Center-Particulate Matter (WTC-PM) exposure are not well described and are therefore the focus of this investigation. C57Bl/6 female mice oropharyngeally aspirated 200 µg of WTC-PM53 or phosphate-buffered saline (PBS) (controls). 24-hours (24-hrs) and 1-Month (1-M) after exposure, echocardiography, micro-positron emission tomography(µ-PET), collagen quantification, lung metabolomics, assessment of antioxidant potential and soluble-receptor for advanced glycation end products (sRAGE) in bronchoalveolar lavage(BAL) and plasma were performed. 24-hrs post-exposure, there was a significant reduction in (1) Pulmonary artery(PA) flow-velocity and pulmonary ejection time(PET) (2) Pulmonary acceleration time(PAT) and PAT/PET, while (3) Aortic ejection time(AET) and velocity time integral(VTI) were increased, and (4) Aortic acceleration time (AAT)/AET, cardiac output and stroke volume were decreased compared to controls. 1-M post-exposure, there was also significant reduction of right ventricular diameter as right ventricle free wall thickness was increased and an increase in tricuspid E, A peaks and an elevated E/A. The pulmonary and cardiac standard uptake value and volume 1-M post-exposure was significantly elevated after PM-exposure. Similarly, α-smooth muscle actin(α-SMA) expression, aortic collagen deposition was elevated 1-M after PM exposure. In assessment of the metabolome, prominent subpathways included advanced glycation end products (AGEs), phosphatidylcholines, sphingolipids, saturated/unsaturated fatty acids, eicosanoids, and phospholipids. BAL superoxide dismutase(SOD), plasma total-antioxidant capacity activity, and sRAGE (BAL and plasma) were elevated after 24-hrs. PM exposure and associated vascular disease are a global health burden. Our study shows persistent WTC-Cardiorespiratory and Vascular Dysfunction (WTC-CaRVD), inflammatory changes and attenuation of antioxidant potential after PM exposure. Early detection of vascular disease is crucial to preventing cardiovascular deaths and future work will focus on further identification of bioactive therapeutic targets.
New insights into cheddar cheese microbiota-metabolome relationships revealed by integrative analysis of multi-omics data
Authors: Afshari Roya , Pillidge Christopher J. , Read Elizabeth , Rochfort Simone , Dias Daniel A. , Osborn A. Mark , Gill Harsharn
Published: February 2020

Cheese microbiota and metabolites and their inter-relationships that underpin specific cheese quality attributes remain poorly understood. Here we report that multi-omics and integrative data analysis (multiple co-inertia analysis, MCIA) can be used to gain deeper insights into these relationships and identify microbiota and metabolite fingerprints that could be used to monitor product quality and authenticity. Our study into different brands of artisanal and industrial cheddar cheeses showed that Streptococcus, Lactococcus and Lactobacillus were the dominant taxa with overall microbial community structures differing not only between industrial and artisanal cheeses but also among different cheese brands. Metabolome analysis also revealed qualitative and semi-quantitative differences in metabolites between different cheeses. This also included the presence of two compounds (3-hydroxy propanoic acid and O-methoxycatechol-O-sulphate) in artisanal cheese that have not been previously reported in any type of cheese. Integrative analysis of multi-omics datasets revealed that highly similar cheeses, identical in age and appearance, could be distinctively clustered according to cheese type and brand. Furthermore, the analysis detected strong relationships, some previously unknown, which existed between the cheese microbiota and metabolome, and uncovered specific taxa and metabolites that contributed to these relationships. These results highlight the potential of this approach for identifying product specific microbe/metabolite signatures that could be used to monitor and control cheese quality and product authenticity.
Low frequency transcranial magnetic stimulation of right posterior parietal cortex reduces reaction time to perithreshold low spatial frequency visual stimuli
Authors: Elkin-Frankston Seth , Rushmore Richard J. , Valero-Cabré Antoni
Published: February 2020

Research in humans and animal models suggests that visual responses in early visual cortical areas may be modulated by top-down influences from distant cortical areas, particularly in the frontal and parietal regions. The right posterior parietal cortex is part of a broad cortical network involved in aspects of visual search and attention, but its role in modulating activity in early visual cortical areas is less well understood. This study evaluated the influence of right posterior parietal cortex (PPC) on a direct measure of visual processing in humans. Contrast sensitivity (CS) and detection response times were recorded using a visual detection paradigm to two types of centrally-presented stimuli. Participants were tested on the detection task before, after, and 1 hour after low-frequency repetitive transcranial magnetic stimulation (rTMS) to the right PPC or to the scalp vertex. Low-frequency rTMS to the right PPC did not significantly change measures of contrast sensitivity, but increased the speed at which participants responded to visual stimuli of low spatial frequency. Response times returned to baseline 1-hour after rTMS. These data indicate that low frequency rTMS to the right PPC speeds up aspects of early visual processing, likely due to a disinhibition of the homotopic left posterior parietal cortex.
Folding intermediate states of the parallel human telomeric G-quadruplex DNA explored using Well-Tempered Metadynamics
Authors: Rocca Roberta , Palazzesi Ferruccio , Amato Jussara , Costa Giosuè , Ortuso Francesco , Pagano Bruno , Randazzo Antonio , Novellino Ettore , Alcaro Stefano , Moraca Federica , Artese Anna
Published: February 2020

An increasingly comprehension of the folding intermediate states of DNA G-quadruplexes (G4s) is currently an important scientific challenge, especially for the human telomeric (h-tel) G4s-forming sequences, characterized by a highly polymorphic nature. Despite the G-triplex conformation was proposed as one of the possible folding intermediates for the antiparallel and hybrid h-tel G4s, for the parallel h-tel topology with an all-anti guanine orientation, a vertical strand-slippage involving the G-triplets was proposed in previous works through microseconds-long standard molecular dynamics simulations (MDs). Here, in order to get further insights into the vertical strand-slippage and the folding intermediate states of the parallel h-tel G4s, we have carried out a Well-Tempered Metadynamics simulation (WT-MetaD), which allowed us to retrieve an ensemble of six G4s having two/G-tetrad conformations derived by the G-triplets vertical slippage. The insights highlighted in this work are aimed at rationalizing the mechanistic characterisation of the parallel h-tel G4 folding process.
Age of puberty and Sleep duration: Observational and Mendelian randomization study
Authors: Wang Jiao , Kwok Man Ki , Au Yeung Shiu Lun , Zhao Jie , Li Albert Martin , Lam Hugh Simon , Leung Gabriel Matthew , Schooling Catherine Mary
Published: February 2020

Earlier age of puberty has detrimental consequences for many aspects of health. Here, for the first time, we assessed the association of earlier puberty with sleep duration observationally and with validation using Mendelian Randomization. In the “Children of 1997” birth cohort (n = 8,327), we used adjusted multivariable logistic regression to assess the associations of each clinically assessed marker of earlier puberty with self-report sleep duration in adolescence. Using two-sample MR, we assessed the effect of earlier puberty timing based on 203 single nucleotide polymorphisms applied to genome wide association studies of sleep duration in adults (n = 335,410). In “Children of 1997”, cross-sectionally, older age of menarche was associated with longer (9+ hours) sleep duration [odds ratio (OR) 1.11, 95% confidence interval (CI) 1.01 to 1.21] at 13.5 years. The other earlier puberty markers were unrelated to sleep duration. Using inverse variance weighting, later of age at menarche increased adult sleep duration [0.020 per category, 95% CI 0.006 to 0.034]. This study demonstrated a causal effect of age at menarche on adult sleep duration, since age of menarche also affects obesity, our novel finding may be relevant to the observed relation of sleep duration with obesity and poor health.
Resting State Functional Connectivity of the Thalamus in North Korean Refugees with and without Posttraumatic Stress Disorder
Authors: Jeon Sehyun , Lee Yu Jin , Park Inkyung , Kim Nambeom , Kim Soohyun , Jun Jin Yong , Yoo So Young , Lee So Hee , Kim Seog Ju
Published: February 2020

In posttraumatic stress disorder (PTSD), functional connectivity (FC) between the thalamus and other brain areas has yet to be comprehensively investigated. The present study explored resting state FC (rsFC) of thalamus and its associations with trauma-related features. The included subjects were North Korean refugees with PTSD (n = 23), trauma-exposed North Korean refugees without PTSD (trauma-exposed control [TEC] group, n = 22), and South Korean healthy controls (HCs) without traumatic experiences (HC group, n = 40). All participants underwent psychiatric evaluation and functional magnetic resonance imaging (fMRI) procedures using the bilateral thalamus as seeds. In the TEC group, the negative rsFC between each thalamus and its contralateral postcentral cortex was stronger relative to the PTSD and HC groups, while positive rsFC between the left thalamus and left precentral cortex was stronger in the HC group compared to the PTSD and TEC groups. Thalamo-postcentral rsFC was positively correlated with the CAPS total score in the TEC group, and with the number of traumatic experiences in the PTSD group. The present study identified the difference of thalamic rsFC alterations among traumatized refugees and HCs. Negative rsFC between the thalamus and somatosensory cortices might be compensatory changes after multiple traumatic events in refugees.
Publisher Correction: Rapid Adaptation to the Timbre of Natural Sounds
Authors: Piazza Elise A. , Theunissen Frédéric E. , Wessel David , Whitney David
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher Correction: Triple-marker cardiac MRI detects sequential tissue changes of healing myocardium after a hydrogel-based therapy
Authors: van den Boomen Maaike , Kause Hanne B. , van Assen Hans C. , Dankers Patricia Y. W. , Bouten Carlijn V. C. , Vandoorne Katrien
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Real-time Metagenomic Analysis of Undiagnosed Fever Cases Unveils a Yellow Fever Outbreak in Edo State, Nigeria
Authors: Ajogbasile Fehintola V. , Oguzie Judith U. , Oluniyi Paul E. , Eromon Philomena E. , Uwanibe Jessica N. , Mehta Samar B. , Siddle Katherine J. , Odia Ikponmwosa , Winnicki Sarah M. , Akpede Nosa , Akpede George , Okogbenin Sylvanus , Ogbaini-Emovon Ephraim , MacInnis Bronwyn L. , Folarin Onikepe A. , Modjarrad Kayvon , Schaffner Stephen F. , Tomori Oyewale , Ihekweazu Chikwe , Sabeti Pardis C. , Happi Christian T.
Published: February 2020

Fifty patients with unexplained fever and poor outcomes presented at Irrua Specialist Teaching Hospital (ISTH) in Edo State, Nigeria, an area endemic for Lassa fever, between September 2018 - January 2019. After ruling out Lassa fever, plasma samples from these epidemiologically-linked cases were sent to the African Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer’s University, Ede, Osun State, Nigeria, where we carried out metagenomic sequencing which implicated yellow fever virus (YFV) as the etiology of this outbreak. Twenty-nine of the 50 samples were confirmed positive for YFV by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), 14 of which resulted in genome assembly. Maximum likelihood phylogenetic analysis revealed that these YFV sequences formed a tightly clustered clade more closely related to sequences from Senegal than sequences from earlier Nigerian isolates, suggesting that the YFV clade responsible for this outbreak in Edo State does not descend directly from the Nigerian YFV outbreaks of the last century, but instead reflects a broader diversity and dynamics of YFV in West Africa. Here we demonstrate the power of metagenomic sequencing for identifying ongoing outbreaks and their etiologies and informing real-time public health responses, resulting in accurate and prompt disease management and control.
High-energy, Long-cycle-life Secondary Battery with Electrochemically Pre-doped Silicon Anode
Authors: Wang Ying , Satoh Masaharu , Arao Masazumi , Matsumoto Masashi , Imai Hideto , Nishihara Hiroshi
Published: February 2020

Electrochemical pre-doping of a silicon electrode was investigated to create a new class of rechargeable battery with higher energy density. The electrochemical reaction during pre-doping formed a high-quality solid electrolyte interface (SEI) on the surface of silicon particles, which improved the charge and discharge cycle life with a small irreversible capacity. The surface composition of the pre-doped silicon particles was characterized using transmission electron microscopy (TEM), solid state magic-angle-spinning (MAS) nuclear magnetic resonance (NMR) and X-ray diffraction analysis (XRD). Pressurization promoted SEI growth and lithium binding with silicon to form Li15Si4 accompanied by the reductive reaction product of Li2CO3 originated from electrolyte. The Li15Si4 was highly stable when the silicon anode was used in a full cell, thus resulting in a silicon anode with a long cycle life.
Abrogation of type-I interferon signalling alters the microglial response to Aβ1–42
Authors: Moore Zachery , Mobilio Frank , Walker Frederick R. , Taylor Juliet M. , Crack Peter J.
Published: February 2020

Neuroinflammation and accompanying microglial dysfunction are now appreciated to be involved in Alzheimer’s disease (AD) pathogenesis. Critical to the process of neuroinflammation are the type-I interferon (IFN) family of cytokines. Efforts to phenotypically characterize microglia within AD identify distinct populations associated with type-I IFN signalling, yet how this affects underlying microglial function is yet to be fully elucidated. Here we demonstrate that Aβ1–42 exposure increases bioactive levels of type-I IFN produced by primary microglia alongside increased expression of type-I IFN related genes. Primary microglia isolated from brains of APPswePS1ΔE9 mice with ablated type-I IFN signalling show an increased phagocytic ability to uptake FITC-Aβ1–42. Correlative assessment of plaque sizes in aged APPswePS1ΔE9 mice with abrogated type-I IFN signalling show unchanged deposition levels. Microglia from these mice did however show alterations in morphology. This data further highlights the role of type-I IFN signalling within microglia and identifies a role in phagocytosis. As such, targeting both microglial and global type-I IFN signalling presents as a novel therapeutic strategy for AD management.
Analysis tools to quantify dissemination of pathology in zebrafish larvae
Authors: Stirling David R. , Suleyman Oniz , Gil Eliza , Elks Philip M. , Torraca Vincenzo , Noursadeghi Mahdad , Tomlinson Gillian S.
Published: February 2020

We describe new open source software called QuantiFish for rapid quantitation of fluorescent foci in zebrafish larvae, to support infection research in this animal model. QuantiFish extends the conventional measurements of bacterial load and number of bacterial foci to include measures for dissemination of infection. These are represented by the proportions of bacteria between foci and their spatial distribution. We showcase these measures by comparison of intravenous and hindbrain routes ofMycobacterium marinuminfection, which are indistinguishable by measurement of bacterial load and not consistently differentiated by the number of bacterial foci. The intravenous route showed dose dependent dissemination of infection, reflected by increased spatial dispersion of bacteria and lower proportions of bacteria distributed across many foci. In contrast, hindbrain infection resulted in localised disease, limited to a smaller area and higher proportions of bacteria distributed across fewer foci. The application of QuantiFish may extend beyond models of infection, to study other pathologies such as metastatic cancer.