bluuebunny/crossref_metadata_2025 huggingface dataset:
RADIOCARBON DATING THE 3RD MILLENNIUM BC IN THE CENTRAL BALKANS: A RE-EXAMINATION OF THE EARLY BRONZE AGE SEQUENCE
Authors: Bulatović Aleksandar , Gori Maja , Vander Linden Marc
Published: July 2020

Long-standing archaeological narratives suggest that the 3rd millennium cal BC is a key period in Mediterranean and European prehistory, characterized by the development of extensive interaction networks. In the Balkans for instance, the identification of such interactions relies solely upon typological arguments associated with conflicting local terminologies. Through a combination of 25 new radiocarbon (14C) dates and re-examination of the existing documentation, this paper defines the absolute chronology for groups which were previously only broadly framed into the 3rd millennium BC central Balkans (modern-day Serbia and North Macedonia). These absolute dates allow us to establish with greater clarity the chronological relations between different cultural groups that represent the main cultural units of the central Balkans sequence for the 3rd millennium cal BC: Coţofeni-Kostolac, Bubanj-Hum II, Belotić-Bela Crkva, Armenochori, and Bubanj Hum III. When comparing together the chronologies for material culture, funerary treatment of the body, and funerary architecture, there are no easily discernible patterns. We observe instead a complex mix of traits criss-crossing over a wide area encompassing the Pannonian basin, the central Balkans and the Greek peninsula.
Does polymorphisms in PPAR and APOE genes modify associations between fatty acid desaturase (FADS), n-3 long-chain PUFA and cardiometabolic markers in 8–11-year-old Danish children?
Authors: Damsgaard Camilla T. , Vuholm Stine , Teisen Marie N. , Stark Ken D. , Lauritzen Lotte
Published: July 2020

n-3 Long-chain PUFA (LCPUFA) can improve cardiometabolic blood markers, but studies in children are limited. SNP in the FADS genes, which encode fatty acid desaturases, influence endogenous LCPUFA production. Moreover, SNP in genes that encode PPAR and apoE may modulate the effects of n-3 LCPUFA. We explored whether FADS polymorphisms were associated with blood cholesterol and TAG, insulin and glucose and whether polymorphisms in PPAR and APOE modified associations between FADS or n-3 LCPUFA status and the cardiometabolic blood markers. We measured fasting cholesterol and TAG, insulin, glucose and n-3 LCPUFA in 757 Danish 8–11-year-old children and genotyped SNP in FADS (rs1535 and rs174448), PPARG2 (rs1801282), PPARA (rs1800206) and APOE (rs7412+rs429358). Carriage of two FADS rs174448 major alleles was associated with lower TAG (P = 0·027) and higher HDL-cholesterol (P = 0·047). Blood n-3 LCPUFA was inversely associated with TAG and insulin in PPARG2 minor allele carriers and positively with LDL-cholesterol in major allele homozygotes (Pn-3 LCPUFA × rs180182 < 0·01). Associations between n-3 LCPUFA and cardiometabolic markers were not modified by APOE genotype (Pn-3 LCPUFA × APOE > 0·11), but interaction between FADS rs1535 and APOE showed that rs1535 major allele homozygotes who also carried APOE2 had higher HDL-cholesterol than all other genotype combinations (Prs1535 × APOE = 0·019, pairwise-P < 0·05). This indicates that FADS genotypes, which increase endogenous LCPUFA production, may beneficially affect children’s cardiometabolic profile in a partly APOE-dependent manner. Also, the degree to which children benefit from higher n-3 LCPUFA intake may depend on their PPARG2 genotype.
Higher flavonoid intake is associated with a lower progression risk of non-alcoholic fatty liver disease in adults: a prospective study
Authors: Zhong Qing-wei , Wu Yan-yan , Xiong Feng , Liu Meng , Liu Yu-ping , Wang Cheng , Chen Yu-ming
Published: July 2020

Flavonoid-rich foods have shown a beneficial effect against non-alcoholic fatty liver disease (NAFLD) in short-term randomised trials. It is uncertain whether the usual dietary intake of flavonoids may benefit patients with NAFLD. The present study evaluated the association between the usual intake of flavonoids and the risk of progression in NAFLD. The prospective study included 2694 adults from the Guangzhou Nutrition and Health Study. Face-to-face interviews using a seventy-nine-item FFQ were administered to assess habitual dietary flavonoid intake, while abdominal ultrasonography was conducted to evaluate the presence and degree of NAFLD, with measurements conducted 3 years apart. After adjustment for potential confounders, higher flavonoid intakes were gradely associated with reduced risks of worsen NAFLD status. The relative risks of worsening (v. non-worsening) NAFLD in the highest (v. lowest) quintile were 0·71 (95 % CI 0·54, 0·93) for total flavonoids, 0·74 (95 % CI 0·57, 0·95) for flavanones, 0·74 (95 % CI 0·56, 0·96) for flavan-3-ols, 0·90 (95 % CI 0·68, 1·18) for flavonols, 0·73 (95 % CI 0·56, 0·93) for flavones, 0·79 (95 % CI 0·61, 1·02) for isoflavones and 0·74 (95 % CI 0·57, 0·96) for anthocyanins. An L-shaped relationship was observed between total flavonoid intake and the risk of NAFLD progression. Path analyses showed that the association between flavonoids and NAFLD progression was mediated by decreases in serum cholesterol and homeostasis model assessment of insulin resistance. This prospective study showed that higher flavonoid intake was associated with a lower risk of NAFLD progression in the elderly overweight/obese Chinese population.
Cochlear nerve canal stenosis and associated semicircular canal abnormalities in paediatric sensorineural hearing loss: a single centre study
Authors: Zainol Abidin Z , Mohd Zaki F , Kew T Y , Goh B S , Abdullah A
Published: July 2020

Objective

This study aimed to evaluate the association between cochlear nerve canal dimensions and semicircular canal abnormalities and to determine the distribution of bony labyrinth anomalies in patients with cochlear nerve canal stenosis.

Method

This was a retrospective study in which high-resolution computed tomography images of paediatric patients with severe-to-profound sensorineural hearing loss were reviewed. A cochlear nerve canal diameter of 1.5 mm or less in the axial plane was classified as stenotic. Semicircular canals and other bony labyrinth morphology and abnormality were evaluated.

Results

Cochlear nerve canal stenosis was detected in 65 out of 265 ears (24 per cent). Of the 65 ears, 17 ears had abnormal semicircular canals (26 per cent). Significant correlation was demonstrated between cochlear nerve canal stenosis and semicircular canal abnormalities (p < 0.01). Incomplete partition type II was the most common accompanying abnormality of cochlear nerve canal stenosis (15 out of 65, 23 per cent).

Conclusion

Cochlear nerve canal stenosis is statistically associated with semicircular canal abnormalities. Whenever a cochlear nerve canal stenosis is present in a patient with sensorineural hearing loss, the semicircular canal should be scrutinised for presence of abnormalities.
Psychological morbidity among adults with cerebral palsy and spina bifida
Authors: Peterson Mark D. , Lin Paul , Kamdar Neil , Mahmoudi Elham , Marsack-Topolewski Christina N. , Haapala Heidi , Muraszko Karin , Hurvitz Edward A.
Published: July 2020

Background

Very little is known about the risk of developing psychological morbidities among adults living with cerebral palsy (CP) or spina bifida (SB). The objective of this study was to compare the incidence of and adjusted hazards for psychological morbidities among adults with and without CP or SB.

Methods

Privately insured beneficiaries were included if they had an International Classification of Diseases, Ninth revision, Clinical Modification diagnostic code for CP or SB (n = 15 302). Adults without CP or SB were also included (n = 1 935 480). Incidence estimates of common psychological morbidities were compared at 4-years of enrollment. Survival models were used to quantify unadjusted and adjusted hazard ratios for incident psychological morbidities.

Results

Adults living with CP or SB had a higher 4-year incidence of any psychological morbidity (38.8% v. 24.2%) as compared to adults without CP or SB, and differences were to a clinically meaningful extent. Fully adjusted survival models demonstrated that adults with CP or SB had a greater hazard for any psychological morbidity [hazard ratio (HR): 1.60; 95% CI 1.55–1.65], and all but one psychological disorder (alcohol-related disorders), and ranged from HR: 1.32 (1.23, 1.42) for substance disorders, to HR: 4.12 (3.24, 5.25) for impulse control disorders.

Conclusions

Adults with CP or SB have a significantly higher incidence of and risk for common psychological morbidities, as compared to adults without CP or SB. Efforts are needed to facilitate the development of improved clinical screening algorithms and early interventions to reduce the risk of disease onset/progression in these higher-risk populations.
‘Sejong the Great would turn in his grave!’
Authors: Kim Sugene
Published: July 2020

The newly renovated Seoul Express Bus Terminal, which reopened at the end of 2019, has caused an uproar among the South Korean public. The fact that its ticket booth sign is written only in English – ‘TICKETS’ – was pointed out by one Twitter user (see Figure 1), and the message went viral among internet users. It took only a week or so for the issue to make headlines in Yonhap News – one of the major news agencies in South Korea (hereafter ‘Korea’) that provides news articles and pictures for newspapers, TV networks, and online media. The news article criticised that not only the ticket booth sign but also the sign of a nearby drug store is written exclusively in English – ‘pharmacy’.
Reconsidering maternal mortality in medieval England: aristocratic Englishwomen, c. 1236–1503
Authors: Podd Rachel
Published: July 2020

The characterisation of medieval childbirth as profoundly dangerous is both long-standing and poorly supported by quantitative data. This article, based on a database tracking the reproductive lives of 102 late medieval aristocratic Englishwomen, allows not only for an evaluation of this trope but also an analysis of risk factors, including maternal youth and short birth intervals. Supplemented with evidence from medieval medical tracts and osteoarchaeological data related to pubertal development and nutrition, this study demonstrates that reproduction was hardly the main driver of mortality among elite women.
Incidental diagnosis of four pulmonary arteriovenous fistulas during patent foramen ovale closure: a case report
Authors: Andreis Alessandro , Agnoletti Gabriella , Scacciatella Paolo
Published: July 2020

Cryptogenic cerebral ischemia in young patients is commonly ascribed to paradoxical embolism. We report the clinical case of a young patient with cryptogenic stroke and a patent foramen ovale, undergoing percutaneous closure of atrial septal defect. Contrast transoesophageal echocardiography at the end of the procedure demonstrated massive late residual right-to-left shunt, due to the coexistence of pulmonary arteriovenous fistulas that were subsequently closed. Routinary adoption of contrast transoesophageal echocardiography at the end of patent foramen ovale closure interventions may be useful to detect early and late residual shunts. Late residual shunts may be due to pulmonary fistulas, a well-known risk factor for recurrent thromboembolic events.
The Late Miocene to Early Pliocene “Humid Interval” on the NW Australian Shelf: Disentangling Climate Forcing From Regional Basin Evolution
Authors: Karatsolis B.‐Th. , De Vleeschouwer D. , Groeneveld J. , Christensen B. , Henderiks J.
Published: July 2020

Pre‐Quaternary paleoclimate studies in Australia mainly focus on terrestrial records from the southeastern part of the continent. IODP Expedition 356 drilled on the northwestern Australian shelf, yielding Miocene‐Pleistocene paleoclimate records in an area where climate archives are scarce. Postexpedition research revealed a dry‐to‐humid transition across the latest Miocene and early Pliocene (start of the “Humid Interval”). However, the complex tectonic history of the area makes these interpretations challenging. In this study, we investigate late Miocene to early Pliocene sediment cores from two sites that are only 100 km apart but situated in two adjacent basins (Northern Carnarvon and Roebuck Basins). Combining lithofacies study, time series analysis of potassium content (K wt%), and calcareous nannofossil abundance counts (N/g), this work disentangles the complex interplay between basin evolution and climate change between 6.1 and 4 Ma. Overall, the investigated proxies show high correlation between both sites, except during 6.1–5.7 Ma. During this interval, Site U1463 records a gradual increase in K wt%, correlated with basin deepening, whereas Site U1464 records an abrupt rise in K wt% at ~6 Ma. We explain this diachronicity by differential basin subsidence. The tectonic interplay with our paleorecords makes it difficult to pinpoint the exact onset of the “Humid Interval,” but we conclude that K wt% and coccolith abundances at Site U1464 indicate that a fluvial deposition system was already established since at least 6 Ma. This age is consistent with data supporting a southward movement of the Intertropical Convergence Zone rain belt at ~7 Ma.
A Geochemical Record of Late‐Holocene Hurricane Events From the Florida Everglades
Authors: Yao Qiang , Liu Kam‐biu , Rodrigues Erika , Bianchette Thomas , Aragón‐Moreno Alejandro Antonio , Zhang Zhenqing
Published: July 2020

A 5.25‐m sediment core SRM‐1 and 45 surface samples from mangrove forests at the Shark River Estuary in the Everglades National Park, Florida, were examined by using X‐ray fluorescence and carbon isotopic analyses to study the history of intense hurricane landfall during the Late‐Holocene. Significance testing of the surface samples in relation to storm deposits from Hurricane Wilma suggests that elemental concentration of Sr and Cl and the ratio of Cl/Br are the most sensitive indicators for major hurricane events in our study area. The geochemical data sets of core SRM‐1 identified five active periods of intense hurricane activities during the last 3,500 years at ~3,400–3,000, ~2,200–1,500, ~1,000–800, ~600–300, and ~150 calibrated years before present to present. This is the longest paleohurricane record to date from South Florida. Our results are consistent with the view that intense hurricane activities in South Florida were modulated by Intertropical Convergence Zone (ITCZ) movements, El Niño/Southern Oscillation (ENSO) activities, and North Atlantic Oscillation (NAO) strength. This study contributes to the methodological advancement in paleotempestological studies by demonstrating that geochemical signals, particularly signals of saltwater intrusions, can be preserved in the sediment profiles on millennial time‐scale and measured by X‐ray fluorescence techniques, thereby enabling more storm records to be produced from otherwise suboptimal sand‐limited coastal systems such as the Florida Everglades. More work needs to be done to explore the use of geochemical and stable isotopic analyses in detecting storm signals from sand‐limited coastal environments.
Effects of Low‐Carbon Energy Adoption on Airborne Particulate Matter Concentrations With Feedbacks to Future Climate Over California
Authors: Kumar Anikender , Zapata Christina , Yeh Sonia , Yang Chris , Ogden Joan , Lee Hsiang‐He , Chen Shu‐Hua , Kleeman Michael J.
Published: July 2020

California plans to reduce emissions of long‐lived greenhouse gases (GHGs) through adoption of new energy systems that will also lower concentrations of short‐lived absorbing soot contained in airborne particulate matter (PM). Here we examine the direct and indirect effects of reduced PM concentrations under a low‐carbon energy (GHG‐Step) scenario on radiative forcing in California. Simulations were carried out using the source‐oriented WRF/Chem (SOWC) model with 12 km spatial resolution for the year 2054. The avoided aerosol emissions due to technology advances in the GHG‐Step scenario reduce ground level PM concentrations by ~8.85% over land compared to the Business‐as‐Usual (BAU) scenario, but changes to meteorological parameters are more modest. Top‐of‐atmospheric forcing predicted by the SOWC model increased by 0.15 W m−2, surface temperature warmed by 0.001 K, and planetary boundary layer height (PBLH) increased by 2.20 cm in the GHG‐Step scenario compared to the BAU scenario. PM climate feedbacks are small because the significant changes in ground level PM concentrations associated with the GHG‐Step scenario are limited to the first few hundred meters of the atmosphere, with little change for the majority of the vertical column above that level. As an order‐of‐magnitude comparison, the long‐term effects of global reductions in GHG emissions (RCP8.5–RCP4.5) lowered average surface temperature over the California study domain by approximately 0.76 K. The effects of long‐lived climate pollutants such as CO2 are much stronger than the effects of short‐lived climate pollutants such as PM soot over California in the year 2054.
The Oxygen Isotope Compositions of Large Numbers of Small Cosmic Spherules: Implications for Their Sources and the Isotopic Composition of the Upper Atmosphere
Authors: Rudraswami N. G. , Genge Matthew J. , Marrocchi Yves , Villeneuve Johan , Taylor S.
Published: July 2020

Cosmic spherules are micrometeorites that melt at high altitude as they enter Earth's atmosphere, and their oxygen isotope compositions are partially or completely inherited from the upper atmosphere, depending on the amount of heating experienced and the nature of their precursor materials. In this study, the three oxygen isotope compositions of 137 cosmic spherules are determined using 277 in situ analyses by ion probe. Our results indicate a possible correlation between increasing average δ18O compositions of silicate‐dominated (S‐type) spherules along the series scoriaceous < porphyritic < barred < cryptocrystalline < glass < CAT (calcium‐aluminum‐titanium) spherules (~12‰, 20‰, 22‰, 25‰, 26‰, and 50‰). This is consistent with the evolution of oxygen isotopes by mass fractionation owing to increased average entry heating and thus suggests mass fractionation dominates changes in isotopic composition, with atmospheric exchange being less significant. The Δ17O values of spherules, therefore, are mostly preserved and suggest that ~80% of particles are samples of C‐type asteroids. The genetic relationships between different S‐types can also be determined with scoriaceous, barred, and cryptocrystalline spherules mostly having low Δ17O values (≤0‰) mainly derived from carbonaceous chondrite (CC)‐like sources, while porphyritic spherules mostly have positive Δ17O (>0‰) and are largely derived from ordinary chondrite (OC)‐like sources related to S (IV)‐type asteroids. Glass and CAT spherules have variable Δ17O values indicating they formed by intense entry heating of both CC and OC‐like materials. I‐type cosmic spherules have a narrow range of δ17O (~20–25‰) and δ18O (~38–48‰) values, with Δ17O (~0‰) suggesting their oxygen is obtained entirely from the Earth's atmosphere, albeit with significant mass fractionation owing to evaporative heating. Finally, G‐type cosmic spherules have unexpected isotopic compositions and demonstrate little mass fractionation from a CC‐like source. The results of this study provide a vital assessment of the wider population of extraterrestrial dust arriving on Earth.
Evidence for a Diagenetic Origin of Vera Rubin Ridge, Gale Crater, Mars: Summary and Synthesis of Curiosity's Exploration Campaign
Authors: Fraeman A. A. , Edgar L. A. , Rampe E. B. , Thompson L. M. , Frydenvang J. , Fedo C. M. , Catalano J. G. , Dietrich W. E. , Gabriel T. S. J. , Vasavada A. R. , Grotzinger J. P. , L'Haridon J. , Mangold N. , Sun V. Z. , House C. H. , Bryk A. B. , Hardgrove C. , Czarnecki S. , Stack K. M. , Morris R. V. , Arvidson R. E. , Banham S. G. , Bennett K. A. , Bridges J. C. , Edwards C. S. , Fischer W. W. , Fox V. K. , Gupta S. , Horgan B. H. N. , Jacob S. R. , Johnson J. R. , Johnson S. S. , Rubin D. M. , Salvatore M. R. , Schwenzer S. P. , Siebach K. L. , Stein N. T. , Turner S. M. R. , Wellington D. F. , Wiens R. C. , Williams A. J. , David G. , Wong G. M.
Published: July 2020

This paper provides an overview of the Curiosity rover's exploration at Vera Rubin ridge (VRR) and summarizes the science results. VRR is a distinct geomorphic feature on lower Aeolis Mons (informally known as Mount Sharp) that was identified in orbital data based on its distinct texture, topographic expression, and association with a hematite spectral signature. Curiosity conducted extensive remote sensing observations, acquired data on dozens of contact science targets, and drilled three outcrop samples from the ridge, as well as one outcrop sample immediately below the ridge. Our observations indicate that strata composing VRR were deposited in a predominantly lacustrine setting and are part of the Murray formation. The rocks within the ridge are chemically in family with underlying Murray formation strata. Red hematite is dispersed throughout much of the VRR bedrock, and this is the source of the orbital spectral detection. Gray hematite is also present in isolated, gray‐colored patches concentrated toward the upper elevations of VRR, and these gray patches also contain small, dark Fe‐rich nodules. We propose that VRR formed when diagenetic event(s) preferentially hardened rocks, which were subsequently eroded into a ridge by wind. Diagenesis also led to enhanced crystallization and/or cementation that deepened the ferric‐related spectral absorptions on the ridge, which helped make them readily distinguishable from orbit. Results add to existing evidence of protracted aqueous environments at Gale crater and give new insight into how diagenesis shaped Mars' rock record.
The roles of multifunctional protein ErbB3 binding protein 1 (EBP1) isoforms from development to disease
Authors: Hwang Inwoo , Ko Hyo Rim , Ahn Jee-Yin
Published: July 2020

The roles of the two isoforms of ErbB3-binding protein 1 (Ebp1) in cellular function and its regulation in disease and development is a stimulating area in current fields of biology, such as neuroscience, cancer biology, and structural biology. Over the last two decades, a growing body of studies suggests have suggested different functions for the EBP1 isoforms in various cancers, along with their specific binding partners in the ubiquitin-proteasome system. Owing to the specific cellular context or spatial/temporal expression of the EBP1 isoforms, either transcriptional repression or the activation function of EBP1 has been proposed, and epigenetic regulation by p48 EBP1 has also been observed during in the embryo development, including in brain development and neurologic disorders, such as schizophrenia, in using an Ebp1 knockout mouse model. Here, we review recent findings that have shaped our current understanding of the emerging function of EBP1 isoforms in cellular events and gene expression, from development to disease.
Computational technology for nasal cartilage-related clinical research and application
Authors: Shi Bing , Huang Hanyao
Published: July 2020

Surgeons need to understand the effects of the nasal cartilage on facial morphology, the function of both soft tissues and hard tissues and nasal function when performing nasal surgery. In nasal cartilage-related surgery, the main goals for clinical research should include clarification of surgical goals, rationalization of surgical methods, precision and personalization of surgical design and preparation and improved convenience of doctor–patient communication. Computational technology has become an effective way to achieve these goals. Advances in three-dimensional (3D) imaging technology will promote nasal cartilage-related applications, including research on computational modelling technology, computational simulation technology, virtual surgery planning and 3D printing technology. These technologies are destined to revolutionize nasal surgery further. In this review, we summarize the advantages, latest findings and application progress of various computational technologies used in clinical nasal cartilage-related work and research. The application prospects of each technique are also discussed.
Photonic amorphous topological insulator
Authors: Zhou Peiheng , Liu Gui-Geng , Ren Xin , Yang Yihao , Xue Haoran , Bi Lei , Deng Longjiang , Chong Yidong , Zhang Baile
Published: July 2020

The current understanding of topological insulators and their classical wave analogs, such as photonic topological insulators, is mainly based on topological band theory. However, standard band theory does not apply to amorphous phases of matter, which are formed by non-crystalline lattices with no long-range positional order but only short-range order, exhibiting unique phenomena such as the glass-to-liquid transition. Here, we experimentally investigate amorphous variants of a Chern number-based photonic topological insulator. By tuning the disorder strength in the lattice, we demonstrate that photonic topological edge states can persist into the amorphous regime prior to the glass-to-liquid transition. After the transition to a liquid-like lattice configuration, the signatures of topological edge states disappear. This interplay between topology and short-range order in amorphous lattices paves the way for new classes of non-crystalline topological photonic bandgap materials.
Bioinspired microcone-array-based living biointerfaces: enhancing the anti-inflammatory effect and neuronal network formation
Authors: Chen Hongxu , Wang Lulu , Lu Yi , Du Xuemin
Published: July 2020

Implantable neural interfaces and systems have attracted much attention due to their broad applications in treating diverse neuropsychiatric disorders. However, obtaining a long-term reliable implant-neural interface is extremely important but remains an urgent challenge due to the resulting acute inflammatory responses. Here, bioinspired microcone-array-based (MA) interfaces have been successfully designed, and their cytocompatibility with neurons and the inflammatory response have been explored. Compared with smooth control samples, MA structures cultured with neuronal cells result in much denser extending neurites, which behave similar to creepers, wrapping tightly around the microcones to form complex and interconnected neuronal networks. After further implantation in mouse brains for 6 weeks, the MA probes (MAPs) significantly reduced glial encapsulation and neuron loss around the implants, suggesting better neuron viability at the implant-neural interfaces than that of smooth probes. This bioinspired strategy for both enhanced glial resistance and neuron network formation via a specific structural design could be a platform technology that not only opens up avenues for next-generation artificial neural networks and brain-machine interfaces but also provides universal approaches to biomedical therapeutics.
Testing relationships between multimodal modes of brain structural variation and age, sex and polygenic scores for neuroticism in children and adolescents
Authors: Norbom Linn B. , Rokicki Jaroslav , Meer Dennis van der , Alnæs Dag , Doan Nhat Trung , Moberget Torgeir , Kaufmann Tobias , Andreassen Ole A. , Westlye Lars T. , Tamnes Christian K.
Published: July 2020

Human brain development involves spatially and temporally heterogeneous changes, detectable across a wide range of magnetic resonance imaging (MRI) measures. Investigating the interplay between multimodal MRI and polygenic scores (PGS) for personality traits associated with mental disorders in youth may provide new knowledge about typical and atypical neurodevelopment. We derived independent components across cortical thickness, cortical surface area, and grey/white matter contrast (GWC) (n = 2596, 3–23 years), and tested for associations between these components and age, sex and-, in a subsample (n = 878), PGS for neuroticism. Age was negatively associated with a single-modality component reflecting higher global GWC, and additionally with components capturing common variance between global thickness and GWC, and several multimodal regional patterns. Sex differences were found for components primarily capturing global and regional surface area (boys > girls), but also regional cortical thickness. For PGS for neuroticism, we found weak and bidirectional associations with a component reflecting right prefrontal surface area. These results indicate that multimodal fusion is sensitive to age and sex differences in brain structure in youth, but only weakly to polygenic load for neuroticism.
PRMT5 promotes cancer cell migration and invasion through the E2F pathway
Authors: Barczak Wojciech , Jin Li , Carr Simon Mark , Munro Shonagh , Ward Samuel , Kanapin Alexander , Samsonova Anastasia , La Thangue Nicholas B.
Published: July 2020

The pRb-E2F pathway is a critical point of regulation in the cell cycle and loss of control of the pathway is a hallmark of cancer. E2F1 is the major target through which pRb exerts its effects and arginine methylation by PRMT5 plays a key role in dictating E2F1 activity. Here we have explored the functional role of the PRMT5-E2F1 axis and highlight its influence on different aspects of cancer cell biology including viability, migration, invasion and adherence. Through a genome-wide expression analysis, we identified a distinct set of genes under the control of PRMT5 and E2F1, including some highly regulated genes, which influence cell migration, invasio and adherence through a PRMT5-dependent mechanism. Most significantly, a coincidence was apparent between the expression of PRMT5 and E2F1 in human tumours, and elevated levels of PRMT5 and E2F1 correlated with poor prognosis disease. Our results suggest a causal relationship between PRMT5 and E2F1 in driving the malignant phenotype and thereby highlight an important pathway for therapeutic intervention.
Altered mitochondrial dynamics and function in APOE4-expressing astrocytes
Authors: Schmukler Eran , Solomon Shira , Simonovitch Shira , Goldshmit Yona , Wolfson Eya , Michaelson Daniel Morris , Pinkas-Kramarski Ronit
Published: July 2020

APOE4 is a major risk factor for sporadic Alzheimer’s disease; however, it is unclear how it exerts its pathological effects. Others and we have previously shown that autophagy is impaired in APOE4 compared to APOE3 astrocytes, and demonstrated differences in the expression of mitochondrial dynamics proteins in brains of APOE3 and APOE4 transgenic mice. Here, we investigated the effect of APOE4 expression on several aspects of mitochondrial function and network dynamics, including fusion, fission, and mitophagy, specifically in astrocytes. We found that APOE3 and APOE4 astrocytes differ in their mitochondrial dynamics, suggesting that the mitochondria of APOE4 astrocytes exhibit reduced fission and mitophagy. APOE4 astrocytes also show impaired mitochondrial function. Importantly, the autophagy inducer rapamycin enhanced mitophagy and improved mitochondrial functioning in APOE4 astrocytes. Collectively, the results demonstrate that APOE4 expression is associated with altered mitochondrial dynamics, which might lead to impaired mitochondrial function in astrocytes. This, in turn, may contribute to the pathological effects of APOE4 in Alzheimer’s disease.
Immune checkpoint inhibitor induces cardiac injury through polarizing macrophages via modulating microRNA-34a/Kruppel-like factor 4 signaling
Authors: Xia Wenzheng , Zou Changlin , Chen Hanbin , Xie Congying , Hou Meng
Published: July 2020

Cancer immunotherapy has become a well-established treatment option for some cancers; however, its use is hampered by its cardiovascular adverse effects. Immune checkpoint inhibitors (ICIs)-related cardiac toxicity took place in kinds of different forms, such as myocarditis, acute coronary syndrome, and pericardial disease, with high mortality rates. This study aimed to investigate the roles of programmed death-1 (PD-1) inhibitor, one of widespread used ICIs, in the development of murine cardiac injury. PD-1 inhibitor is known to transduce immunoregulatory signals that modulate macrophages polarization to attack tumor cells. Hence, this study explored whether the cardiovascular adverse effects of PD-1 inhibitor were related to macrophage polarization. MicroRNA-34a (miR-34a), which appears to regulate the polarization of cultured macrophages to induce inflammation, is examined in cardiac injury and macrophage polarization induced by the PD-1 inhibitor. As a target of miR-34a, Krüppel-like factor 4 (KLF4) acted as an anti-inflammation effector to take cardiac protective effect. Further, it investigated whether modulating the miR-34a/KLF4-signaling pathway could influence macrophage polarization. The PD-1 inhibitor markedly induced M1 phenotype macrophage polarization with impaired cardiac function, whereas miR-34a inhibitor transfection treatment reversed M1 polarization and cardiac injury in vivo. In vitro, PD-1 inhibitor-induced M1 polarization was accompanied by an increase in the expression of miR-34a but a decrease in the expression of KLF4. TargetScan and luciferase assay showed that miR-34a targeted the KLF4 3′-untranslated region. Either miR-34a inhibition or KLF4 overexpression could abolish M1 polarization induced by the PD-1 inhibitor. The findings strongly suggested that the PD-1 inhibitor exerted its effect in promoting M1 polarization and cardiac injury by modulating the miR-34a/KLF4-signaling pathway and inducing myocardial inflammation. These findings might help us to understand the pathogenesis of cardiac injury during immunotherapy, and provide new targets in ameliorating cardiac injury in patients with cancer receiving PD-1 inhibitor treatment.
Roles of aminoacyl-tRNA synthetase-interacting multi-functional proteins in physiology and cancer
Authors: Zhou Zheng , Sun Bao , Huang Shiqiong , Yu Dongsheng , Zhang Xiaochuan
Published: July 2020

Aminoacyl-tRNA synthetases (ARSs) are an important class of enzymes with an evolutionarily conserved mechanism for protein synthesis. In higher eukaryotic systems, eight ARSs and three ARS-interacting multi-functional proteins (AIMPs) form a multi-tRNA synthetase complex (MSC), which seems to contribute to cellular homeostasis. Of these, AIMPs are generally considered as non-enzyme factors, playing a scaffolding role during MSC assembly. Although the functions of AIMPs are not fully understood, increasing evidence indicates that these scaffold proteins usually exert tumor-suppressive activities. In addition, endothelial monocyte-activating polypeptide II (EMAP II), as a cleavage product of AIMP1, and AIMP2-DX2, as a splice variant of AIMP2 lacking exon 2, also have a pivotal role in regulating tumorigenesis. In this review, we summarize the biological functions of AIMP1, EMAP II, AIMP2, AIMP2-DX2, and AIMP3. Also, we systematically introduce their emerging roles in cancer, aiming to provide new ideas for the treatment of cancer.
HMGA2 regulates circular RNA ASPH to promote tumor growth in lung adenocarcinoma
Authors: Xu Li , Ma Ye , Zhang Hua , Lu Qi-Jue , Yang Lie , Jiang Ge-Ning , Liao Wei-Lin
Published: July 2020

In this study, we identified a circular form of ASPH RNA (circASPH), expression of which was upregulated in lung adenocarcinoma and the human lung adenocarcinoma cell lines. We also found a positive correlation between circASPH level and the T and N stages of lung adenocarcinoma patients. Patients with higher levels of circASPH had a shorter overall survival. Moreover, we demonstrated that circASPH was directly regulated by HMGA2 and Twist1. The direct positive regulation of circASPH by Twist1 was dependent on the presence of HMGA2. Functional assays indicated that circASPH promoted the proliferation, migration, and invasion of lung adenocarcinoma cell lines in vitro. The promoting effect of tumor growth by circASPH was also observed in vivo. Mechanistically, circASPH was identified to act as a molecular sponge for miR-370 and abrogate miR-370-mediated inhibition of HMGA2. Finally, we demonstrated that the oncogenic function of circASPH was HMGA2-dependent. These findings reveal the oncogenic functions of the HMGA2-circASPH-HMGA2 axis and may be useful in developing circRNA-based therapeutic strategies for lung adenocarcinoma.
The sugar transporter system of strawberry: genome-wide identification and expression correlation with fruit soluble sugar-related traits in a Fragaria × ananassa germplasm collection
Authors: Liu Hai-Ting , Ji Ying , Liu Ya , Tian Shu-Hua , Gao Qing-Hua , Zou Xiao-Hua , Yang Jing , Dong Chao , Tan Jia-Hui , Ni Di-An , Duan Ke
Published: July 2020

Sugar from plant photosynthesis is a basic requirement for life activities. Sugar transporters are the proteins that mediate sugar allocation among or within source/sink organs. The transporters of the major facilitator superfamily (MFS) targeting carbohydrates represent the largest family of sugar transporters in many plants. Strawberry (Fragaria × ananassa Duchesne) is an important crop appreciated worldwide for its unique fruit flavor. The involvement of MFS sugar transporters (STs) in cultivated strawberry fruit sugar accumulation is largely unknown. In this work, we characterized the genetic variation associated with fruit soluble sugars in a collection including 154 varieties. Then, a total of 67 ST genes were identified in the v4.0 genome integrated with the v4.0.a2 protein database of F. vesca, the dominant subgenome provider for modern cultivated strawberry. Phylogenetic analysis updated the nomenclature of strawberry ST homoeologs. Both the chromosomal distribution and structural characteristics of the ST family were improved. Semi-RT-PCR analysis in nine tissues from cv. Benihoppe screened 34 highly expressed ST genes in fruits. In three varieties with dramatically differing fruit sugar levels, qPCR integrated with correlation analysis between ST transcript abundance and sugar content identified 13 sugar-correlated genes. The correlations were re-evaluated across 19 varieties, including major commercial cultivars grown in China. Finally, a model of the contribution of the sugar transporter system to subcellular sugar allocation in strawberry fruits was proposed. Our work highlights the involvement of STs in controlling strawberry fruit soluble sugars and provides candidates for the future functional study of STs in strawberry development and responses and a new approach for strawberry genetic engineering and molecular breeding.
High-throughput production of cheap mineral-based two-dimensional electrocatalysts for high-current-density hydrogen evolution
Authors: Zhang Chi , Luo Yuting , Tan Junyang , Yu Qiangmin , Yang Fengning , Zhang Zhiyuan , Yang Liusi , Cheng Hui-Ming , Liu Bilu
Published: July 2020

The high-throughput scalable production of cheap, efficient and durable electrocatalysts that work well at high current densities demanded by industry is a great challenge for the large-scale implementation of electrochemical technologies. Here we report the production of a two-dimensional molybdenum disulfide-based ink-type electrocatalyst by a scalable exfoliation technique followed by a thermal treatment. The catalyst delivers a high current density of 1000 mA cm−2at an overpotential of 412 mV for the hydrogen evolution. Using the same method, we produce a cheap mineral-based catalyst possessing excellent performance for high-current-density hydrogen evolution. Noteworthy, production rate of this catalyst is one to two orders of magnitude higher than those previously reported, and price of the mineral is five orders of magnitude lower than commercial Pt electrocatalysts. These advantages indicate the huge potentials of this method and of mineral-based cheap and abundant natural resources as catalysts in the electrochemical industry.
Discovery of an unrecognized pathway carrying overflow waters toward the Faroe Bank Channel
Authors: Chafik Léon , Hátún Hjálmar , Kjellsson Joakim , Larsen Karin Margretha H. , Rossby Thomas , Berx Barbara
Published: July 2020

The dense overflow waters of the Nordic Seas are an integral link and important diagnostic for the stability of the Atlantic Meridional Overturning Circulation (AMOC). The pathways feeding the overflow remain, however, poorly resolved. Here we use multiple observational platforms and an eddy-resolving ocean model to identify an unrecognized deep flow toward the Faroe Bank Channel. We demonstrate that anticyclonic wind forcing in the Nordic Seas via its regulation of the basin circulation plays a key role in activating an unrecognized overflow path from the Norwegian slope – at which times the overflow is anomalously strong. We further establish that, regardless of upstream pathways, the overflows are mostly carried by a deep jet banked against the eastern slope of the Faroe-Shetland Channel, contrary to previous thinking. This deep flow is thus the primary conduit of overflow water feeding the lower branch of the AMOC via the Faroe Bank Channel.
Preparation of TiH1.924 nanodots by liquid-phase exfoliation for enhanced sonodynamic cancer therapy
Authors: Gong Fei , Cheng Liang , Yang Nailin , Gong Yuehan , Ni Yanwen , Bai Shang , Wang Xianwen , Chen Muchao , Chen Qian , Liu Zhuang
Published: July 2020

Metal hydrides have been rarely used in biomedicine. Herein, we fabricate titanium hydride (TiH1.924) nanodots from its powder form via the liquid-phase exfoliation, and apply these metal hydride nanodots for effective cancer treatment. The liquid-phase exfoliation is an effective method to synthesize these metal hydride nanomaterials, and its efficiency is determined by the matching of surface energy between the solvent and the metal hydrides. The obtained TiH1.924 nanodots can produce reactive oxygen species (ROS) under ultrasound, presenting a highly efficient sono-sensitizing effect. Meanwhile, TiH1.924 nanodots with strong near-infrared (NIR) absorbance can serve as a robust photothermal agent. By using the mild photothermal effect to enhance intra-tumoral blood flow and improve tumor oxygenation, a remarkable synergistic therapeutic effect is achieved in the combined photothermal-sonodynamic therapy. Importantly, most of these TiH1.924 nanodots can be cleared out from the body. This work presents the promises of functional metal hydride nanomaterials for biomedical applications.
Long-lasting severe immune dysfunction in Ebola virus disease survivors
Authors: Wiedemann Aurélie , Foucat Emile , Hocini Hakim , Lefebvre Cécile , Hejblum Boris P. , Durand Mélany , Krüger Miriam , Keita Alpha Kabinet , Ayouba Ahidjo , Mély Stéphane , Fernandez José-Carlos , Touré Abdoulaye , Fourati Slim , Lévy-Marchal Claire , Raoul Hervé , Delaporte Eric , Koivogui Lamine , Thiébaut Rodolphe , Lacabaratz Christine , Lévy Yves ,   PostEboGui Study Group, Ayouba Ahidjo , Delaporte Eric , Keita Alpha Kabinet , Koivogui Lamine , Lacabaratz Christine , Marchal Claire Levy , Levy Yves , Raoul Hervé , Touré Abdoulaye
Published: July 2020

Long-term follow up studies from Ebola virus disease (EVD) survivors (EBOV_S) are lacking. Here, we evaluate immune and gene expression profiles in 35 Guinean EBOV_S from the last West African outbreak, a median of 23 months (IQR [18–25]) after discharge from treatment center. Compared with healthy donors, EBOV_S exhibit increases of blood markers of inflammation, intestinal tissue damage, T cell and B cell activation and a depletion of circulating dendritic cells. All survivors have EBOV-specific IgG antibodies and robust and polyfunctional EBOV-specific memory T-cell responses. Deep sequencing of the genes expressed in blood reveals an enrichment in ‘inflammation’ and ‘antiviral’ pathways. Integrated analyses identify specific immune markers associated with the persistence of clinical symptoms. This study identifies a set of biological and genetic markers that could be used to define a signature of “chronic Ebola virus disease (CEVD)”.
Li2CO3-affiliative mechanism for air-accessible interface engineering of garnet electrolyte via facile liquid metal painting
Authors: Meng Junwei , Zhang Yang , Zhou Xuejun , Lei Meng , Li Chilin
Published: July 2020

Garnet based solid-state batteries have the advantages of wide electrochemical window and good chemical stability. However, at Li-garnet interface, the poor interfacial wettability due to Li2CO3 passivation usually causes large resistance and unstable contact. Here, a Li2CO3-affiliative mechanism is proposed for air-accessible interface engineering of garnet electrolyte via facile liquid metal (LM) painting. The natural LM oxide skin enables a superior wettability of LM interlayer towards ceramic electrolyte and Li anode. Therein the removal of Li2CO3 passivation network is not necessary, in view of its delamination and fragmentation by LM penetration. This dissipation effect allows the lithiated LM nanodomains to serve as alternative Li-ion flux carriers at Li-garnet interface. This mechanism leads to an interfacial resistance as small as 5 Ω cm2 even after exposing garnet in air for several days. The ultrastable Li plating and stripping across LM painted garnet can last for 9930 h with a small overpotential.
Structural basis of RNA cap modification by SARS-CoV-2
Authors: Viswanathan Thiruselvam , Arya Shailee , Chan Siu-Hong , Qi Shan , Dai Nan , Misra Anurag , Park Jun-Gyu , Oladunni Fatai , Kovalskyy Dmytro , Hromas Robert A. , Martinez-Sobrido Luis , Gupta Yogesh K.
Published: July 2020

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19 illness, has caused millions of infections worldwide. In SARS coronaviruses, the non-structural protein 16 (nsp16), in conjunction with nsp10, methylates the 5′-end of virally encoded mRNAs to mimic cellular mRNAs, thus protecting the virus from host innate immune restriction. We report here the high-resolution structure of a ternary complex of SARS-CoV-2 nsp16 and nsp10 in the presence of cognate RNA substrate analogue and methyl donor, S-adenosyl methionine (SAM). The nsp16/nsp10 heterodimer is captured in the act of 2′-O methylation of the ribose sugar of the first nucleotide of SARS-CoV-2 mRNA. We observe large conformational changes associated with substrate binding as the enzyme transitions from a binary to a ternary state. This induced fit model provides mechanistic insights into the 2′-O methylation of the viral mRNA cap. We also discover a distant (25 Å) ligand-binding site unique to SARS-CoV-2, which can alternatively be targeted, in addition to RNA cap and SAM pockets, for antiviral development.
Patients with immune-mediated inflammatory diseases receiving cytokine inhibitors have low prevalence of SARS-CoV-2 seroconversion
Authors: Simon David , Tascilar Koray , Krönke Gerhard , Kleyer Arnd , Zaiss Mario M. , Heppt Franz , Meder Christine , Atreya Raja , Klenske Entcho , Dietrich Peter , Abdullah Abdullah , Kliem Thorsten , Corte Giulia , Morf Harriet , Leppkes Moritz , Kremer Andreas E. , Ramming Andreas , Pachowsky Milena , Schuch Florian , Ronneberger Monika , Kleinert Stefan , Maier Clara , Hueber Axel J. , Manger Karin , Manger Bernhard , Berking Carola , Tenbusch Matthias , Überla Klaus , Sticherling Michael , Neurath Markus F. , Schett Georg
Published: July 2020

Immune-mediated inflammatory diseases (IMIDs) of the joints, gut and skin are treated with inhibitors of inflammatory cytokines. These cytokines are involved in the pathogenesis of coronavirus disease 2019 (COVID-19). Investigating anti-SARS-CoV-2 antibody responses in IMIDs we observe a reduced incidence of SARS-CoV-2 seroconversion in IMID patients treated with cytokine inhibitors compared to patients receiving no such inhibitors and two healthy control populations, despite similar social exposure. Hence, cytokine inhibitors seem to at least partially protect from SARS-CoV-2 infection.