bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface cooling caused by rare but intense near-inertial wave induced mixing in the tropical Atlantic
Authors: Hummels Rebecca , Dengler Marcus , Rath Willi , Foltz Gregory R. , Schütte Florian , Fischer Tim , Brandt Peter
Published: July 2020

The direct response of the tropical mixed layer to near-inertial waves (NIWs) has only rarely been observed. Here, we present upper-ocean turbulence data that provide evidence for a strongly elevated vertical diffusive heat flux across the base of the mixed layer in the presence of a NIW, thereby cooling the mixed layer at a rate of 244 W m−2 over the 20 h of continuous measurements. We investigate the seasonal cycle of strong NIW events and find that despite their local intermittent nature, they occur preferentially during boreal summer, presumably associated with the passage of atmospheric African Easterly Waves. We illustrate the impact of these rare but intense NIW induced mixing events on the mixed layer heat balance, highlight their contribution to the seasonal evolution of sea surface temperature, and discuss their potential impact on biological productivity in the tropical North Atlantic.
A distal regulatory region of a class I human histone deacetylase
Authors: Werbeck Nicolas D. , Shukla Vaibhav Kumar , Kunze Micha B. A. , Yalinca Havva , Pritchard Ruth B. , Siemons Lucas , Mondal Somnath , Greenwood Simon O. R. , Kirkpatrick John , Marson Charles M. , Hansen D. Flemming
Published: July 2020

Histone deacetylases (HDACs) are key enzymes in epigenetics and important drug targets in cancer biology. Whilst it has been established that HDACs regulate many cellular processes, far less is known about the regulation of these enzymes themselves. Here, we show that HDAC8 is allosterically regulated by shifts in populations between exchanging states. An inactive state is identified, which is stabilised by a range of mutations and resembles a sparsely-populated state in equilibrium with active HDAC8. Computational models show that the inactive and active states differ by small changes in a regulatory region that extends up to 28 Å from the active site. The regulatory allosteric region identified here in HDAC8 corresponds to regions in other class I HDACs known to bind regulators, thus suggesting a general mechanism. The presented results pave the way for the development of allosteric HDAC inhibitors and regulators to improve the therapy for several disease states.
A nanoscale metal organic frameworks-based vaccine synergises with PD-1 blockade to potentiate anti-tumour immunity
Authors: Li Xia , Wang Xiupeng , Ito Atsuo , Tsuji Noriko M.
Published: July 2020

Checkpoint blockade therapy has provided noteworthy benefits in multiple cancers in recent years; however, its clinical benefits remain confined to 10–40% of patients with extremely high costs. Here, we design an ultrafast, low-temperature, and universal self-assembly route to integrate immunology-associated large molecules into metal-organic-framework (MOF)-gated mesoporous silica (MS) as cancer vaccines. Core MS nanoparticles, acting as an intrinsic immunopotentiator, provide the niche, void, and space to accommodate antigens, soluble immunopotentiators, and so on, whereas the MOF gatekeeper protects the interiors from robust and off-target release. A combination of MOF-gated MS cancer vaccines with systemic programmed cell death 1 (PD-1) blockade therapy generates synergistic effects that potentiate antitumour immunity and reduce the effective dose of an anti-PD-1 antibody to as low as 1/10 of that for PD-1 blockade monotherapy in E.G7-OVA tumour-bearing mice, with eliciting the robust adaptive OVA-specific CD8+ T-cell responses, reversing the immunosuppressive pathway and inducing durable tumour suppression.
Testing and controlling for horizontal pleiotropy with probabilistic Mendelian randomization in transcriptome-wide association studies
Authors: Yuan Zhongshang , Zhu Huanhuan , Zeng Ping , Yang Sheng , Sun Shiquan , Yang Can , Liu Jin , Zhou Xiang
Published: July 2020

Integrating results from genome-wide association studies (GWASs) and gene expression studies through transcriptome-wide association study (TWAS) has the potential to shed light on the causal molecular mechanisms underlying disease etiology. Here, we present a probabilistic Mendelian randomization (MR) method, PMR-Egger, for TWAS applications. PMR-Egger relies on a MR likelihood framework that unifies many existing TWAS and MR methods, accommodates multiple correlated instruments, tests the causal effect of gene on trait in the presence of horizontal pleiotropy, and is scalable to hundreds of thousands of individuals. In simulations, PMR-Egger provides calibrated type I error control for causal effect testing in the presence of horizontal pleiotropic effects, is reasonably robust under various types of model misspecifications, is more powerful than existing TWAS/MR approaches, and can directly test for horizontal pleiotropy. We illustrate the benefits of PMR-Egger in applications to 39 diseases and complex traits obtained from three GWASs including the UK Biobank.
Designer patterned functional fibers via direct imprinting in thermal drawing
Authors: Wang Zhe , Wu Tingting , Wang Zhixun , Zhang Ting , Chen Mengxiao , Zhang Jing , Liu Lin , Qi Miao , Zhang Qichong , Yang Jiao , Liu Wei , Chen Haisheng , Luo Yu , Wei Lei
Published: July 2020

Creating micro/nanostructures on fibers is beneficial for extending the application range of fiber-based devices. To achieve this using thermal fiber drawing is particularly important for the mass production of longitudinally uniform fibers up to tens of kilometers. However, the current thermal fiber drawing technique can only fabricate one-directional micro/nano-grooves longitudinally due to structure elongation and polymer reflow. Here, we develop a direct imprinting thermal drawing (DITD) technique to achieve arbitrarily designed surface patterns on entire fiber surfaces with high resolution in all directions. Such a thermal imprinting process is simulated and confirmed experimentally. Key process parameters are further examined, showing a process feature size as small as tens of nanometers. Furthermore, nanopatterns are fabricated on fibers as plasmonic metasurfaces, and double-sided patterned fibers are produced to construct self-powered wearable touch sensing fabric, revealing the bright future of the DITD technology in multifunctional fiber-based devices, wearable electronics, and smart textiles.
European polygenic risk score for prediction of breast cancer shows similar performance in Asian women
Authors: Ho Weang-Kee , Tan Min-Min , Mavaddat Nasim , Tai Mei-Chee , Mariapun Shivaani , Li Jingmei , Ho Peh-Joo , Dennis Joe , Tyrer Jonathan P. , Bolla Manjeet K. , Michailidou Kyriaki , Wang Qin , Kang Daehee , Choi Ji-Yeob , Jamaris Suniza , Shu Xiao-Ou , Yoon Sook-Yee , Park Sue K. , Kim Sung-Won , Shen Chen-Yang , Yu Jyh-Cherng , Tan Ern Yu , Chan Patrick Mun Yew , Muir Kenneth , Lophatananon Artitaya , Wu Anna H. , Stram Daniel O. , Matsuo Keitaro , Ito Hidemi , Chan Ching Wan , Ngeow Joanne , Yong Wei Sean , Lim Swee Ho , Lim Geok Hoon , Kwong Ava , Chan Tsun L. , Tan Su Ming , Seah Jaime , John Esther M. , Kurian Allison W. , Koh Woon-Puay , Khor Chiea Chuen , Iwasaki Motoki , Yamaji Taiki , Tan Kiak Mien Veronique , Tan Kiat Tee Benita , Spinelli John J. , Aronson Kristan J. , Hasan Siti Norhidayu , Rahmat Kartini , Vijayananthan Anushya , Sim Xueling , Pharoah Paul D. P. , Zheng Wei , Dunning Alison M. , Simard Jacques , van Dam Rob Martinus , Yip Cheng-Har , Taib Nur Aishah Mohd , Hartman Mikael , Easton Douglas F. , Teo Soo-Hwang , Antoniou Antonis C.
Published: July 2020

Polygenic risk scores (PRS) have been shown to predict breast cancer risk in European women, but their utility in Asian women is unclear. Here we evaluate the best performing PRSs for European-ancestry women using data from 17,262 breast cancer cases and 17,695 controls of Asian ancestry from 13 case-control studies, and 10,255 Chinese women from a prospective cohort (413 incident breast cancers). Compared to women in the middle quintile of the risk distribution, women in the highest 1% of PRS distribution have a ~2.7-fold risk and women in the lowest 1% of PRS distribution has ~0.4-fold risk of developing breast cancer. There is no evidence of heterogeneity in PRS performance in Chinese, Malay and Indian women. A PRS developed for European-ancestry women is also predictive of breast cancer risk in Asian women and can help in developing risk-stratified screening programmes in Asia.
Assessing the response of micro-eukaryotic diversity to the Great Acceleration using lake sedimentary DNA
Authors: Keck François , Millet Laurent , Debroas Didier , Etienne David , Galop Didier , Rius Damien , Domaizon Isabelle
Published: July 2020

Long-term time series have provided evidence that anthropogenic pressures can threaten lakes. Yet it remains unclear how and the extent to which lake biodiversity has changed during the Anthropocene, in particular for microbes. Here, we used DNA preserved in sediments to compare modern micro-eukaryotic communities with those from the end of the 19th century, i.e., before acceleration of the human imprint on ecosystems. Our results obtained for 48 lakes indicate drastic changes in the composition of microbial communities, coupled with a homogenization of their diversity between lakes. Remote high elevation lakes were globally less impacted than lowland lakes affected by local human activity. All functional groups (micro-algae, parasites, saprotrophs and consumers) underwent significant changes in diversity. However, we show that the effects of anthropogenic changes have benefited in particular phototrophic and mixotrophic species, which is consistent with the hypothesis of a global increase of primary productivity in lakes.
A joint role for forced and internally-driven variability in the decadal modulation of global warming
Authors: Liguori Giovanni , McGregor Shayne , Arblaster Julie M. , Singh Martin S. , Meehl Gerald A.
Published: July 2020

Despite the observed monotonic increase in greenhouse-gas concentrations, global mean temperature displays important decadal fluctuations typically attributed to both external forcing and internal variability. Here, we provide a robust quantification of the relative contributions of anthropogenic, natural, and internally-driven decadal variability of global mean sea surface temperature (GMSST) by using a unique dataset consisting of 30-member large initial-condition ensembles with five Earth System Models (ESM-LE). We present evidence that a large fraction (~29–53%) of the simulated decadal-scale variance in individual timeseries of GMSST over 1950–2010 is externally forced and largely linked to the representation of volcanic aerosols. Comparison with the future (2010–2070) period suggests that external forcing provides a source of additional decadal-scale variability in the historical period. Given the unpredictable nature of future volcanic aerosol forcing, it is suggested that a large portion of decadal GMSST variability might not be predictable.
Oxygen induced promotion of electrochemical reduction of CO2 via co-electrolysis
Authors: He Ming , Li Chunsong , Zhang Haochen , Chang Xiaoxia , Chen Jingguang G. , Goddard William A. , Cheng Mu-jeng , Xu Bingjun , Lu Qi
Published: July 2020

Harnessing renewable electricity to drive the electrochemical reduction of CO2 is being intensely studied for sustainable fuel production and as a means for energy storage. Copper is the only monometallic electrocatalyst capable of converting CO2 to value-added products, e.g., hydrocarbons and oxygenates, but suffers from poor selectivity and mediocre activity. Multiple oxidative treatments have shown improvements in the performance of copper catalysts. However, the fundamental underpinning for such enhancement remains controversial. Here, we combine reactivity, in-situ surface-enhanced Raman spectroscopy, and computational investigations to demonstrate that the presence of surface hydroxyl species by co-electrolysis of CO2 with low concentrations of O2 can dramatically enhance the activity of copper catalyzed CO2 electroreduction. Our results indicate that co-electrolysis of CO2 with an oxidant is a promising strategy to introduce catalytically active species in electrocatalysis.
T-square resistivity without Umklapp scattering in dilute metallic Bi2O2Se
Authors: Wang Jialu , Wu Jing , Wang Tao , Xu Zhuokai , Wu Jifeng , Hu Wanghua , Ren Zhi , Liu Shi , Behnia Kamran , Lin Xiao
Published: July 2020

Fermi liquids (FLs) display a quadratic temperature (T) dependent resistivity. This can be caused by electron-electron (e-e) scattering in presence of inter-band or Umklapp scattering. However, dilute metallic SrTiO3 was found to display T2 resistivity in absence of either of the two mechanisms. The presence of soft phonons as possible scattering centers raised the suspicion that T2 resistivity is not due to e-e scattering. Here, we present the case of Bi2O2Se, a layered semiconductor with hard phonons, which becomes a dilute metal with a small single-component Fermi surface upon doping. It displays T2 resistivity well below the degeneracy temperature in absence of Umklapp and inter-band scattering. We observe a universal scaling between the T2 resistivity prefactor (A) and the Fermi energy (EF), an extension of the Kadowaki-Woods plot to dilute metals. Our results imply the absence of a satisfactory understanding of the ubiquity of e-e T2 resistivity in FLs.
Protein-responsive protein release of supramolecular/polymer hydrogel composite integrating enzyme activation systems
Authors: Shigemitsu Hajime , Kubota Ryou , Nakamura Keisuke , Matsuzaki Tomonobu , Minami Saori , Aoyama Takuma , Urayama Kenji , Hamachi Itaru
Published: July 2020

Non-enzymatic proteins including antibodies function as biomarkers and are used as biopharmaceuticals in several diseases. Protein-responsive soft materials capable of the controlled release of drugs and proteins have potential for use in next-generation diagnosis and therapies. Here, we describe a supramolecular/agarose hydrogel composite that can release a protein in response to a non-enzymatic protein. A non-enzymatic protein-responsive system is developed by hybridization of an enzyme-sensitive supramolecular hydrogel with a protein-triggered enzyme activation set. In situ imaging shows that the supramolecular/agarose hydrogel composite consists of orthogonal domains of supramolecular fibers and agarose, which play distinct roles in protein entrapment and mechanical stiffness, respectively. Integrating the enzyme activation set with the composite allows for controlled release of the embedded RNase in response to an antibody. Such composite hydrogels would be promising as a matrix embedded in a body, which can autonomously release biopharmaceuticals by sensing biomarker proteins.
Catalytic nanosponges of acidic aluminosilicates for plastic degradation and CO2 to fuel conversion
Authors: Maity Ayan , Chaudhari Sachin , Titman Jeremy J. , Polshettiwar Vivek
Published: July 2020

The synthesis of solid acids with strong zeolite-like acidity and textural properties like amorphous aluminosilicates (ASAs) is still a challenge. In this work, we report the synthesis of amorphous “acidic aluminosilicates (AAS)”, which possesses Brønsted acidic sites like in zeolites and textural properties like ASAs. AAS catalyzes different reactions (styrene oxide ring-opening, vesidryl synthesis, Friedel−Crafts alkylation, jasminaldehyde synthesis, m-xylene isomerization, and cumene cracking) with better performance than state-of-the-art zeolites and amorphous aluminosilicates. Notably, AAS efficiently converts a range of waste plastics to hydrocarbons at significantly lower temperatures. A Cu-Zn-Al/AAS hybrid shows excellent performance for CO2 to fuel conversion with 79% selectivity for dimethyl ether. Conventional and DNP-enhanced solid-state NMR provides a molecular-level understanding of the distinctive Brønsted acidic sites of these materials. Due to their unique combination of strong acidity and accessibility, AAS will be a potential alternative to zeolites.
Anchoring the Late Devonian mass extinction in absolute time by integrating climatic controls and radio-isotopic dating
Authors: Da Silva Anne-Christine , Sinnesael Matthias , Claeys Philippe , Davies Joshua H. F. L. , de Winter Niels J. , Percival L. M. E. , Schaltegger Urs , De Vleeschouwer David
Published: July 2020

The Devonian Frasnian–Famennian (F–F) boundary marks one of the five main extinction intervals of the Phanerozoic Aeon. This time was characterized by two pulses of oceanic anoxia, named the Lower and Upper Kellwasser events, during which massive marine biodiversity losses occurred. This paper presents high-resolution magnetic susceptibility, X-ray fluorescence elemental geochemistry and carbon isotope datasets obtained from the Steinbruch Schmidt F–F boundary section (Germany). These records lead to an astronomical time calibration of the environmental changes associated with the two ocean anoxia pulses. Cyclostratigraphic interpretation indicates deposition of the black argillaceous Lower and Upper Kellwasser horizons over ~ 90 and ~ 110 kyr, respectively; approximately equivalent to the duration of one short eccentricity cycle. This study confirms that the succession of events within the Upper Kellwasser event is paced by obliquity, under a low-eccentricity orbit. Hence, astronomical insolation forcing likely contributed to the expansion of ocean anoxia and other environmental perturbations associated with these two crises. The new floating chronology established for the Steinbruch Schmidt section is anchored in numerical time by means of a radio-isotopic date, obtained from a bentonite layer interbedded between the two Kellwasser horizons. After anchoring, this time scale gives a high-precision age of 371.870 ± 0.108 Ma for the F–F boundary.
Methyl-donor supplementation prevents intestinal colonization by Adherent-Invasive E. coli in a mouse model of Crohn’s disease
Authors: Gimier Elodie , Chervy Mélissa , Agus Allison , Sivignon Adeline , Billard Elisabeth , Privat Maud , Viala Sandrine , Minet-Quinard Régine , Buisson Anthony , Vazeille Emilie , Barnich Nicolas , Denizot Jérémy
Published: July 2020

Deficiencies in methyl-donor molecules (folate, B12 vitamin), DNA methylation alteration and high prevalence of Adherent-Invasive Escherichia coli (AIEC) are frequently observed in Crohn’s disease (CD) patients. AIEC bacteria adhere to the enterocytes through abnormally expressed carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) glycoprotein on host cells. This work aims at studying the relationship between methyl-donor molecules and AIEC-induced intestinal inflammatory response. CEABAC10 mice, a mouse model of CD, were fed a control or Methyl-donor Supplemented diet (MS diet). CEACAM6 promoter was hypermethylated in intestinal epithelial cells from mice fed an MS diet, which was associated with a significant decrease in CEACAM6 expression. Transcriptomic analysis revealed increased expression of anti-microbial peptides, increase in HSP70 gene family expression and a decreased expression of inflammatory marker Calprotectin upon MS diet, associated to a lower ability of AIEC bacteria to colonize gut mucosa. We observed in a cohort of CD patients that serum folate concentration was inversely correlated to Crohn’s disease endoscopic index of severity and to fecal inflammatory markers. This study demonstrates that methyl-donor supplementation through the diet induces a specific intestinal micro-environment limiting pathobiont colonization of the gut. Clinicians may wish to consider methyl-donor supplementation for methyl-donor deficient CD patients.
Non-invasive continuous-time glucose monitoring system using a chipless printable sensor based on split ring microwave resonators
Authors: Baghelani Masoud , Abbasi Zahra , Daneshmand Mojgan , Light Peter E.
Published: July 2020

This paper reports a highly sensitive, non-invasive sensor for real-time glucose monitoring from interstitial fluid. The structure is comprised of a chip-less tag sensor which may be taped over the patient’s skin and a reader, that can be embedded in a smartwatch. The tag sensor is energized through the established electromagnetic coupling between the tag and the reader and its frequency response is reflected on the spectrum of the reader in the same manner. The tag sensor consumes zero power as there is no requirement for any active readout or communication circuitry on the tag side. When measuring changes in glucose concentrations within saline replicating interstitial fluid, the sensor was able to detect glucose with an accuracy of ~ 1 mM/l over a physiological range of glucose concentrations with 38 kHz of the resonance frequency shift. This high sensitivity is attained as a result of the proposed new design and extended field concentration on the tag. The impact of some of the possible interferences on the response of the sensor’s performance was also investigated. Variations in electrolyte concentrations within the test samples have a negligible effect on the response of the sensor unless these variations are supra-physiologically large.
Species composition of the largest shark fin retail-market in mainland China
Authors: Cardeñosa Diego , Fields Andrew T. , Babcock Elizabeth A. , Shea Stanley K. H. , Feldheim Kevin A. , Chapman Demian D.
Published: July 2020

Species-specific monitoring through large shark fin market surveys has been a valuable data source to estimate global catches and international shark fin trade dynamics. Hong Kong and Guangzhou, mainland China, are the largest shark fin markets and consumption centers in the world. We used molecular identification protocols on randomly collected processed fin trimmings (n = 2000) and non-parametric species estimators to investigate the species composition of the Guangzhou retail market and compare the species diversity between the Guangzhou and Hong Kong shark fin retail markets. Species diversity was similar between both trade hubs with a small subset of species dominating the composition. The blue shark (Prionace glauca) was the most common species overall followed by the CITES-listed silky shark (Carcharhinus falciformis), scalloped hammerhead shark (Sphyrna lewini), smooth hammerhead shark (S. zygaena) and shortfin mako shark (Isurus oxyrinchus). Our results support previous indications of high connectivity between the shark fin markets of Hong Kong and mainland China and suggest that systematic studies of other fin trade hubs within Mainland China and stronger law-enforcement protocols and capacity building are needed.
A footprint of plant eco-geographic adaptation on the composition of the barley rhizosphere bacterial microbiota
Authors: Alegria Terrazas Rodrigo , Balbirnie-Cumming Katharin , Morris Jenny , Hedley Pete E. , Russell Joanne , Paterson Eric , Baggs Elizabeth M. , Fridman Eyal , Bulgarelli Davide
Published: July 2020

The microbiota thriving in the rhizosphere, the thin layer of soil surrounding plant roots, plays a critical role in plant’s adaptation to the environment. Domestication and breeding selection have progressively differentiated the microbiota of modern crops from the ones of their wild ancestors. However, the impact of eco-geographical constraints faced by domesticated plants and crop wild relatives on recruitment and maintenance of the rhizosphere microbiota remains to be fully elucidated. Here we performed a comparative 16S rRNA gene survey of the rhizosphere of 4 domesticated and 20 wild barley (Hordeum vulgare) genotypes grown in an agricultural soil under controlled environmental conditions. We demonstrated the enrichment of individual bacteria mirrored the distinct eco-geographical constraints faced by their host plants. Unexpectedly, Elite varieties exerted a stronger genotype effect on the rhizosphere microbiota when compared with wild barley genotypes adapted to desert environments with a preferential enrichment for members of Actinobacteria. Finally, in wild barley genotypes, we discovered a limited, but significant, correlation between microbiota diversity and host genomic diversity. Our results revealed a footprint of the host’s adaptation to the environment on the assembly of the bacteria thriving at the root–soil interface. In the tested conditions, this recruitment cue layered atop of the distinct evolutionary trajectories of wild and domesticated plants and, at least in part, is encoded by the barley genome. This knowledge will be critical to design experimental approaches aimed at elucidating the recruitment cues of the barley microbiota across a range of soil types.
Delay discounting decisions are linked to temporal distance representations of world events across cultures
Authors: Croote Denise E. , Lai Baojun , Hu Jingchu , Baxter Mark G. , Montagrin Alison , Schiller Daniela
Published: July 2020

Delay discounting describes the phenomenon whereby the subjective value of a reward declines as the time until its receipt increases. Individuals differ in the subjective value that they assign to future rewards, yet, the components feeding into this appraisal of value remain unclear. We examined whether temporal psychological distance, i.e. the closeness one feels to the past and future, is one such component. English speakers in the USA and Mandarin speakers in China completed a delay discounting task and organized past and future world events on a canvas according to their representation of the event’s temporal position relative to themselves. Previous work has identified linguistic and cultural differences in time conception between these populations, thus, we hypothesized that this sample would display the variability necessary to probe whether temporal psychological distance plays a role in reward valuation. We found that English speakers employed horizontal, linear representations of world events, while Mandarin speakers used more two-dimensional, circular representations. Across cultures, individuals who represented the future as more distant discounted future rewards more strongly. Distance representations of past events, however, were associated with discounting behaviors selectively in Mandarin speakers. This suggests that temporal psychological distance plays a fundamental role in farsighted decision-making.
Spp24 is associated with endocytic signalling, lipid metabolism, and discrimination of tissue integrity for ‘leaky-gut’ in inflammatory bowel disease
Authors: Wasinger Valerie C. , Lu Kenneth , Yau Yunki Y. , Nash Justin , Lee Jess , Chang Jeff , Paramsothy Sudarshan , Kaakoush Nadeem O. , Mitchell Hazel M. , Leong Rupert W. L.
Published: July 2020

Epithelial barrier injury allows contaminants to cross-over into the blood stream and trigger an inflammatory response, contributing to inflammatory bowel disease (IBD). Currently there is no single test that can reliably diagnose intestinal mucosal barrier function or measure impaired epithelial cell integrity associated with increasing permeability. Here, we assess the association between serum proteins and small intestinal permeability as detected by confocal laser endomicroscopy (CLE); in particular the known IBD marker—secreted phosphoprotein 24 (SPP24) and its binding partners; and use developed monoclonal antibodies to assess the role of SPP24 in mucosal healing. Sera were obtained from 28 IBD patients and non-IBD controls undergoing CLE with scores ranging from low to high permeability, as well as active ulcerative colitis from 53 patients undergoing fecal microbiota transplant therapy (FMT). Higher permeability associated with altered lipid metabolism, heightened innate immune response and junctional protein signalling in UC patients. A correlation between increasing leak and SPP24 peptide was observed. There is a strong indication of the novel role of SPP24 in gut barrier dysfunction particularly in ulcerative colitis. Its correlation to the established CLE for monitoring permeability has the potential to provide a blood based parallel to monitor and guide therapy more readily across a broad spectrum of illnesses for which ‘leak’ dominates the pathology.
Insights into the salivary N-glycome of Lutzomyia longipalpis, vector of visceral leishmaniasis
Authors: Mondragon-Shem Karina , Wongtrakul-Kish Katherine , Kozak Radoslaw P. , Yan Shi , Wilson Iain B. H. , Paschinger Katharina , Rogers Matthew E. , Spencer Daniel I. R. , Acosta-Serrano Alvaro
Published: July 2020

DuringLeishmaniatransmission sand flies inoculate parasites and saliva into the skin of vertebrates. Saliva has anti-haemostatic and anti-inflammatory activities that evolved to facilitate bloodfeeding, but also modulate the host’s immune responses. Sand fly salivary proteins have been extensively studied, but the nature and biological roles of protein-linked glycans remain overlooked. Here, we characterised the profile ofN-glycans from the salivary glycoproteins ofLutzomyia longipalpis, vector of visceral leishmaniasis in the Americas. In silico predictions suggest half ofLu. longipalpissalivary proteins may beN-glycosylated. SDS-PAGE coupled to LC–MS analysis of sand fly saliva, before and after enzymatic deglycosylation, revealed several candidate glycoproteins. To determine the diversity ofN-glycan structures in sand fly saliva, enzymatically released sugars were fluorescently tagged and analysed by HPLC, combined with highly sensitive LC–MS/MS, MALDI-TOF–MS, and exoglycosidase treatments. We found that theN-glycan composition ofLu. longipalpissaliva mostly consists of oligomannose sugars, with Man5GlcNAc2being the most abundant, and a few hybrid-type species. Interestingly, some glycans appear modified with a group of 144 Da, whose identity has yet to be confirmed. Our work presents the first detailed structural analysis of sand fly salivary glycans.
Few-cycle localized plasmon oscillations
Authors: Csete Mária , Szenes András , Vass Dávid , Bánhelyi Balázs , Dombi Péter
Published: July 2020

The generation of few-cycle laser pulses proved to be a key enabling technology in strong-field physics and ultrafast science. The question naturally arises whether one can induce few-cycle localized plasmon oscillations in optical near-fields. Here, we perform a comparative study of different plasmonic nanoresonators illuminated by few-cycle pulses. We analyze the number of cycles (NOC) of the plasmonic field, the near-field enhancement (NFE) as well as the figure of merit NFE/NOC. The pulse length dependence of these quantities is also investigated. Throughout the inspected pulse-length interval silica-gold and silica-silver core–shell monomers have the potential to preserve the NOC of the incoming pulse, silver bow-ties result in the highest NFE, whereas gold core–shell dimers have the highest NFE/NOC. Based on the analysis, silver bow-ties, gold core–shell and silver nanorod dimers proved to be the most suitable for few-cycle near-field amplification.
Vitamin D supplementation effects on the clinical outcomes of patients with coronary artery disease: a systematic review and meta-analysis
Authors: Bahrami Leila Sadat , Ranjbar Golnaz , Norouzy Abdolreza , Arabi Seyyed Mostafa
Published: July 2020

In this systematic review and meta-analysis our aim was to assess the effect of vitamin D supplementation on cardiac outcomes in patients with coronary artery disease (CAD). The search terms were performed from January 2000 to January 2018, only randomized clinical trials (RCT) in human subjects were considered, with no language restrictions. The electronic databases used in this study were: PubMed; Cochran library; Embase; and Scopus. Two independent expert reviewers carried out data extraction according to Cochrane recommendations. Only four RCTs were found in relation to the effects of vitamin D supplementation on the coronary artery disease. In these 299 patients, vitamin D supplementation had significant favorable effects on Diastolic Blood Pressure (DBP) (− 2.96, p = 0.02) and Parathyroid hormone (PTH) (− 4.05, p < 0.001). However, it had no significant effects on hs-CRP mean difference (− 0.04, p = 0.25), total cholesterol (TC) (− 0.46, p = 0.83), triglyceride (TG) (0.68, p = 0.89), low-density lipoproteins (LDL) (2.08, p = 0.56), and high-density lipoproteins (HDL) (− 2.59, p = 0.16). In conclusion, the use of vitamin D was associated with improvements in some cardiac outcomes of CAD patients with vitamin D deficiency. Also, further research is needed to clarify these results.
Dynamical gene regulatory networks are tuned by transcriptional autoregulation with microRNA feedback
Authors: Minchington Thomas G. , Griffiths-Jones Sam , Papalopulu Nancy
Published: July 2020

Concepts from dynamical systems theory, including multi-stability, oscillations, robustness and stochasticity, are critical for understanding gene regulation during cell fate decisions, inflammation and stem cell heterogeneity. However, the prevalence of the structures within gene networks that drive these dynamical behaviours, such as autoregulation or feedback by microRNAs, is unknown. We integrate transcription factor binding site (TFBS) and microRNA target data to generate a gene interaction network across 28 human tissues. This network was analysed for motifs capable of driving dynamical gene expression, including oscillations. Identified autoregulatory motifs involve 56% of transcription factors (TFs) studied. TFs that autoregulate have more interactions with microRNAs than non-autoregulatory genes and 89% of autoregulatory TFs were found in dual feedback motifs with a microRNA. Both autoregulatory and dual feedback motifs were enriched in the network. TFs that autoregulate were highly conserved between tissues. Dual feedback motifs with microRNAs were also conserved between tissues, but less so, and TFs regulate different combinations of microRNAs in a tissue-dependent manner. The study of these motifs highlights ever more genes that have complex regulatory dynamics. These data provide a resource for the identification of TFs which regulate the dynamical properties of human gene expression.
Mutation accumulation and developmental lineages in normal and Down syndrome human fetal haematopoiesis
Authors: Hasaart Karlijn A. L. , Manders Freek , van der Hoorn Marie-Louise , Verheul Mark , Poplonski Tomasz , Kuijk Ewart , de Sousa Lopes Susana M. Chuva , van Boxtel Ruben
Published: July 2020

Children show a higher incidence of leukemia compared to young adolescents, yet their cells have less age-related (oncogenic) somatic mutations. Newborns with Down syndrome have an even higher risk of developing leukemia, which is thought to be driven by mutations that accumulate during fetal development. To characterize mutation accumulation in individual stem and progenitor cells of Down syndrome and karyotypically normal fetuses, we clonally expanded single cells and performed whole-genome sequencing. We found a higher mutation rate in haematopoietic stem and progenitor cells during fetal development compared to the post-infant rate. In fetal trisomy 21 cells the number of somatic mutations is even further increased, which was already apparent during the first cell divisions of embryogenesis before gastrulation. The number and types of mutations in fetal trisomy 21 haematopoietic stem and progenitor cells were similar to those in Down syndrome-associated myeloid preleukemia and could be attributed to mutational processes that were active during normal fetal haematopoiesis. Finally, we found that the contribution of early embryonic cells to human fetal tissues can vary considerably between individuals. The increased mutation rates found in this study, may contribute to the increased risk of leukemia early during life and the higher incidence of leukemia in Down syndrome.
Spatiotemporal characteristics of high-density gas jet and absolute determination of size and density of gas clusters
Authors: Lee Bo Ram , Singh Prashant Kumar , Rhee Yong Joo , Nam Chang Hee
Published: July 2020

Properties of gas clusters such as the size and number density when expanding into the vacuum after passing through a conical nozzle are analyzed for argon at an average density of 1020/cm3. Temporally and spatially resolved size and density distribution were measured from all-optical methods of Rayleigh scattering measurement and Nomarski interferometry using a CW laser. At the gas backing pressure of 80 bar, Ar clusters as large as 100 nm were obtained, which differs significantly from the size estimated by the conventional Hagena scaling law. The two independent methods of cluster characterization presented here would be useful to precisely determine the initial conditions in a variety of intense laser-cluster interaction driven applications such as neutron generation, thermonuclear fusion, efficient x-ray emission, and energetic ion acceleration.
Direct growth of graphene on Ge(100) and Ge(110) via thermal and plasma enhanced CVD
Authors: Bekdüz Bilge , Kaya Umut , Langer Moritz , Mertin Wolfgang , Bacher Gerd
Published: July 2020

The integration of graphene into CMOS compatible Ge technology is in particular attractive for optoelectronic devices in the infrared spectral range. Since graphene transfer from metal substrates has detrimental effects on the electrical properties of the graphene film and moreover, leads to severe contamination issues, direct growth of graphene on Ge is highly desirable. In this work, we present recipes for a direct growth of graphene on Ge via thermal chemical vapor deposition (TCVD) and plasma-enhanced chemical vapor deposition (PECVD). We demonstrate that the growth temperature can be reduced by about 200 °C in PECVD with respect to TCVD, where usually growth occurs close to the melting point of Ge. For both, TCVD and PECVD, hexagonal and elongated morphology is observed on Ge(100) and Ge(110), respectively, indicating the dominant role of substrate orientation on the shape of graphene grains. Interestingly, Raman data indicate a compressive strain of ca. − 0.4% of the graphene film fabricated by TCVD, whereas a tensile strain of up to + 1.2% is determined for graphene synthesized via PECVD, regardless the substrate orientation. Supported by Kelvin probe force measurements, we suggest a mechanism that is responsible for graphene formation on Ge and the resulting strain in TCVD and PECVD.
Publisher Correction: A new viewpoint on antlers reveals the evolutionary history of deer (Cervidae, Mammalia)
Authors: Samejima Yuusuke , Matsuoka Hiroshige
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A comparison of baleen whale density estimates derived from overlapping satellite imagery and a shipborne survey
Authors: Bamford C. C. G. , Kelly N. , Dalla Rosa L. , Cade D. E. , Fretwell P. T. , Trathan P. N. , Cubaynes H. C. , Mesquita A. F. C. , Gerrish L. , Friedlaender A. S. , Jackson J. A.
Published: July 2020

As whales recover from commercial exploitation, they are increasing in abundance in habitats that they have been absent from for decades. However, studying the recovery and habitat use patterns of whales, particularly in remote and inaccessible regions, frequently poses logistical and economic challenges. Here we trial a new approach for measuring whale density in a remote area, using Very-High-Resolution WorldView-3 satellite imagery. This approach has capacity to provide sightings data to complement and assist traditional sightings surveys. We compare at-sea whale density estimates to estimates derived from satellite imagery collected at a similar time, and use suction-cup archival logger data to make an adjustment for surface availability. We demonstrate that satellite imagery can provide useful data on whale occurrence and density. Densities, when unadjusted for surface availability are shown to be considerably lower than those estimated by the ship survey. However, adjusted for surface availability and weather conditions (0.13 whales per km2, CV = 0.38), they fall within an order of magnitude of those derived by traditional line-transect estimates (0.33 whales per km2, CV = 0.09). Satellite surveys represent an exciting development for high-resolution image-based cetacean observation at sea, particularly in inaccessible regions, presenting opportunities for ongoing and future research.
Familiarity with children improves the ability to recognize children’s mental states: an fMRI study using the Reading the Mind in the Eyes Task and the Nencki Children Eyes Test
Authors: Szczypiński Jan , Alińska Anna , Waligóra Marek , Kopera Maciej , Krasowska Aleksandra , Michalska Aneta , Suszek Hubert , Jakubczyk Andrzej , Wypych Marek , Wojnar Marcin , Marchewka Artur
Published: July 2020

Theory of mind plays a fundamental role in human social interactions. People generally better understand the mental states of members of their own race, a predisposition called the own-race bias, which can be significantly reduced by experience. It is unknown whether the ability to understand mental states can be similarly influenced by own-age bias, whether this bias can be reduced by experience and, finally, what the neuronal correlates of this processes are. We evaluate whether adults working with children (WC) have an advantage over adults not working with children (NWC) in understanding the mental states of youngsters. Participants performed fMRI tasks with Adult Mind (AM) and Child Mind (CM) conditions based on the Reading the Mind in the Eyes test and a newly developed Nencki Children Eyes test. WC had better accuracy in the CM condition than NWC. In NWC, own-age bias was associated with higher activation in the posterior superior temporal sulcus (pSTS) in AM than in CM. This effect was not observed in the WC group, which showed higher activation in the pSTS and inferior frontal gyri in CM than in AM. Therefore, activation in these regions is required for the improvement in recognition of children’s mental states caused by experience.
Natural rubber as a renewable carbon source for mesoporous carbon/silica nanocomposites
Authors: Yousatit Satit , Pitayachinchot Hannarong , Wijitrat Apinya , Chaowamalee Supphathee , Nuntang Sakdinun , Soontaranon Siriwat , Rugmai Supagorn , Yokoi Toshiyuki , Ngamcharussrivichai Chawalit
Published: July 2020

This study is the first report on the preparation of mesoporous carbon/silica (MCS) nanocomposites with tunable mesoporosity and hydrophobicity using natural rubber (NR) as a renewable and cheap carbon source. A series of mesoporous nanocomposites based on NR and hexagonal mesoporous silica (HMS) were prepared via an in situ sol–gel process and used as precursors; then, they were converted into MCS materials by controlled carbonization. The NR/HMS precursors exhibited a high dispersion of rubber phase incorporated into the mesostructured silica framework as confirmed by small-angle X-ray scattering and high-resolution transmission electron microscopy. An increase in the carbonization temperature up to 700 °C resulted in MCS nanocomposites with a well-ordered mesostructure and uniform framework-confined wormhole-like channels. The NR/HMS nanocomposites possessed high specific surface area (500–675 m2 g−1) and large pore volume (1.14–1.44 cm3 g−1). The carbon content of MCS (3.0–16.1 wt%) was increased with an increase in the H2SO4 concentration. Raman spectroscopy and X-ray photoelectron spectroscopy revealed the high dispersion of graphene oxide-like carbonaceous moieties in MCS materials; the type and amount of oxygen-containing groups in obtained MCS materials were determined by H2SO4 concentration. The enhanced hydrophobicity of MCS nanocomposites was related to the carbon content and the depletion of surface silanol groups, as confirmed by the water sorption measurement. The study on the controlled release of diclofenac in simulated gastrointestinal environment suggests a potential application of MCS materials as drug carriers.
Evidence of disruption of Si-rich microstructure in engineering-lightweight Al–12.2at.%Si alloy melt above liquidus temperature
Authors: Dong Xixi , Li Peijie , Amirkhanlou Sajjad , Ji Shouxun , Popel Pjotr S. , Dahlborg Ulf , Calvo-Dahlborg Monique
Published: July 2020

The exploration of microstructures in high temperature alloy melts is important for manufacturing of metallic components but extremely challenging. Here, we report experimental evidence of the disruption of Si-rich microstructure in engineering-lightweight Al–12.2at.%Si alloy melt at 1100 °C, via melt-spinning (MS) of Al1−xSix (x = 0.03,0.07,0.122,0.2) alloy melts from different initial melt temperatures, 800 °C and 1100 °C, under the super-high cooling rate of ~ 106 °C/s, in cooperation with the small angle neutron scattering (SANS) measurement. Si particles in 1100 °C MS alloys are abnormally smaller and increased in number at Al–12.2at.%Si, compared with 800 °C MS alloys, which demonstrates the disruption of Si-rich microstructure in Al–12.2at.%Si alloy melt at 1100 °C. SANS experiment verifies that large quantities of small (0–10 nm) Si-rich microstructures and small quantities of large (10–240 nm) Si-rich microstructures exist in Al–12.2at.%Si alloy melt, and the large Si-rich microstructures disrupt into small Si-rich microstructures with increasing of melt temperature from 800 to 1100 °C. Microstructure analysis of the MS alloys indicates that the large Si-rich microstructures in Al–12.2at.%Si alloy melt are probably aggregates comprising multiple small Si-rich microstructures. This work also provides a pathway for the exploration of microstructures in other high temperature alloy melts.
Synergistic drug combinations and machine learning for drug repurposing in chordoma
Authors: Anderson Edward , Havener Tammy M. , Zorn Kimberley M. , Foil Daniel H. , Lane Thomas R. , Capuzzi Stephen J. , Morris Dave , Hickey Anthony J. , Drewry David H. , Ekins Sean
Published: July 2020

Chordoma is a devastating rare cancer that affects one in a million people. With a mean-survival of just 6 years and no approved medicines, the primary treatments are surgery and radiation. In order to speed new medicines to chordoma patients, a drug repurposing strategy represents an attractive approach. Drugs that have already advanced through human clinical safety trials have the potential to be approved more quickly than de novo discovered medicines on new targets. We have taken two strategies to enable this: (1) generated and validated machine learning models of chordoma inhibition and screened compounds of interest in vitro. (2) Tested combinations of approved kinase inhibitors already being individually evaluated for chordoma. Several published studies of compounds screened against chordoma cell lines were used to generate Bayesian Machine learning models which were then used to score compounds selected from the NIH NCATS industry-provided assets. Out of these compounds, the mTOR inhibitor AZD2014, was the most potent against chordoma cell lines (IC50 0.35 µM U-CH1 and 0.61 µM U-CH2). Several studies have shown the importance of the mTOR signaling pathway in chordoma and suggest it as a promising avenue for targeted therapy. Additionally, two currently FDA approved drugs, afatinib and palbociclib (EGFR and CDK4/6 inhibitors, respectively) demonstrated synergy in vitro (CI50 = 0.43) while AZD2014 and afatanib also showed synergy (CI50 = 0.41) against a chordoma cell in vitro. These findings may be of interest clinically, and this in vitro- and in silico approach could also be applied to other rare cancers.
Publisher Correction: Mapping of QTL for Grain Yield Components Based on a DH Population in Maize
Authors: Yang Jiwei , Liu Zonghua , Chen Qiong , Qu Yanzhi , Tang Jihua , Lübberstedt Thomas , Li Haochuan
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.