bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atlas of plasma NMR biomarkers for health and disease in 118,461 individuals from the UK Biobank
Authors: Julkunen Heli , Cichońska Anna , Tiainen Mika , Koskela Harri , Nybo Kristian , Mäkelä Valtteri , Nokso-Koivisto Jussi , Kristiansson Kati , Perola Markus , Salomaa Veikko , Jousilahti Pekka , Lundqvist Annamari , Kangas Antti J. , Soininen Pasi , Barrett Jeffrey C. , Würtz Peter 
Published: February 2023

AbstractBlood lipids and metabolites are markers of current health and future disease risk. Here, we describe plasma nuclear magnetic resonance (NMR) biomarker data for 118,461 participants in the UK Biobank. The biomarkers cover 249 measures of lipoprotein lipids, fatty acids, and small molecules such as amino acids, ketones, and glycolysis metabolites. We provide an atlas of associations of these biomarkers to prevalence, incidence, and mortality of over 700 common diseases (nightingalehealth.com/atlas). The results reveal a plethora of biomarker associations, including susceptibility to infectious diseases and risk of various cancers, joint disorders, and mental health outcomes, indicating that abundant circulating lipids and metabolites are risk markers beyond cardiometabolic diseases. Clustering analyses indicate similar biomarker association patterns across different disease types, suggesting latent systemic connectivity in the susceptibility to a diverse set of diseases. This work highlights the value of NMR based metabolic biomarker profiling in large biobanks for public health research and translation.
Tunable sliding ferroelectricity and magnetoelectric coupling in two-dimensional multiferroic MnSe materials
Authors: Liu Kehan , Ma Xikui , Xu Shuoke , Li Yangyang , Zhao Mingwen 
Published: February 2023

AbstractSliding ferroelectricity (SFE) found in two-dimensional (2D) van der Waals (vdW) materials, such as BN and transition-metal dichalcogenides bilayers, opens an avenue for 2D ferroelectric materials. Multiferroic coupling in 2D SFE materials brings us an alternative concept for spintronic memory devices. In this study, using first-principles calculations, we demonstrate that MnSe multilayers constructed by the recently-synthesized MnSe monolayer have large sliding-driven reversible out-of-plane electric polarization (~10.6 pC m−1) and moderate interlayer sliding barriers superior to the existing 2D SFE materials. Interestingly, the intrinsic electric polarization is accompanied by nonzero net magnetic moments which are also switchable via lateral interlayer sliding. Additionally, both SFE and magnetoelectric coupling can be effectively regulated by external strain and/or hole doping. Our findings suggest the potential of MnSe multilayers in 2D multiferroic and spintronic applications.
Maternal antibodies induced by a live attenuated vaccine protect neonatal mice from cytomegalovirus
Authors: Le-Trilling Vu Thuy Khanh , Jagnjić Andreja , Brizić Ilija , Eilbrecht Mareike , Wohlgemuth Kerstin , Rožmanić Carmen , Herdman Alan , Hoffmann Katja , Westendorf Astrid M. , Hengel Hartmut , Jonjić Stipan , Trilling Mirko 
Published: February 2023

AbstractHuman cytomegalovirus (HCMV) frequently causes congenital infections, resulting in birth defects and developmental disorders. A vaccine is needed, but unavailable. We analyzed the potential of CMV mutants, lacking their STAT2 antagonists to serve as live attenuated vaccine viruses in mice. Infections with attenuated viruses elicited strong ELISA-reactive binding IgG responses and induced neutralizing antibodies as well as antibodies stimulating cellular Fcγ receptors, including the antibody-dependent cellular cytotoxicity (ADCC)-eliciting receptors FcγRIII/CD16 and FcγRIV. Accordingly, vaccinated mice were fully protected against challenge infections. Female mice vaccinated prior to gestation transmitted CMV-specific IgG to their offspring, which protected the progeny from perinatal infections in a mouse model for congenital CMV disease. To define the role of maternal antibodies, female mice either capable or incapable of producing antibodies were vaccinated and subsequently bred to males of the opposite genotype. Challenge infections of the genotypically identical F1 generation revealed the indispensability of maternal antibodies for vaccine-induced protection against cytomegaloviruses.
Disease state associated with chronic toe lesions in hellbenders may alter anti-chytrid skin defenses
Authors: Hardman Rebecca H. , Reinert Laura K. , Irwin Kelly J. , Oziminski Kendall , Rollins-Smith Louise , Miller Debra L. 
Published: February 2023

AbstractHellbenders (Cryptobranchus alleganiensis) are large, aquatic salamanders from the eastern United States. Both subspecies, eastern and Ozark hellbenders, have experienced declines resulting in federal listing of Ozark hellbenders. The globally distributed chytrid fungus,Batrachochytrium dendrobatidis (Bd)has been detected in both subspecies, andBatrachochytrium salamandrivorans(Bsal) poses a new threat if introduced into North America. Ozark hellbenders also suffer a high prevalence of toe lesions of unknown etiology, with changes in host immunocompetence hypothesized to contribute. Antimicrobial peptides (AMPs) secreted from dermal granular glands may play a role in hellbender health. We collected skin secretions from free-ranging hellbenders and enriched them for small cationic peptides used for growth inhibition assays againstBdandBsal. Generalized linear mixed models revealed the presence of active toe lesions as the strongest and only significant predictor of decreasedBdinhibition by skin peptides. We also found skin secretions were more inhibitory ofBsalthanBd. MALDI-TOF mass spectrometry revealed candidate peptides responsible for anti-chytrid activity. Results support the hypothesis that hellbender skin secretions are important for innate immunity against chytrid pathogens, and decreased production or release of skin peptides may be linked to other sub-lethal effects of disease associated with toe lesions.
Self-association of the glycopeptide antibiotic teicoplanin A2 in aqueous solution studied by molecular hydrodynamics
Authors: Chun Taewoo , Pattem Jacob , Gillis Richard B. , Dinu Vlad T. , Yakubov Gleb E. , Corfield Anthony P. , Harding Stephen E. 
Published: February 2023

AbstractThe natural glycopeptide antibiotic teicoplanin is used for the treatment of serious Gram-positive related bacterial infections and can be administered intravenously, intramuscularly, topically (ocular infections), or orally. It has also been considered for targeting viral infection by SARS-CoV-2. The hydrodynamic properties of teicoplanin A2 (M1 = 1880 g/mol) were examined in phosphate chloride buffer (pH 6.8, I = 0.10 M) using sedimentation velocity and sedimentation equilibrium in the analytical ultracentrifuge together with capillary (rolling ball) viscometry. In the concentration range, 0–10 mg/mL teicoplanin A2 was found to self-associate plateauing > 1 mg/mL to give a molar mass of (35,400 ± 1000) g/mol corresponding to ~ (19 ± 1) mers, with a sedimentation coefficient s20, w =  ~ 4.65 S. The intrinsic viscosity [$$\eta$$
η
] was found to be (3.2 ± 0.1) mL/g: both this, the value for s20,w and the hydrodynamic radius from dynamic light scattering are consistent with a globular macromolecular assembly, with a swelling ratio through dynamic hydration processes of ~ 2.
Research on blasting cumulative dynamic damage of surrounding rock in step construction tunnel
Authors: Cui Yaozhong , Wu Bo , Meng Guowang , Xu Shixiang 
Published: February 2023

AbstractIn the process of cyclic blasting during tunnel excavation, the reserved surrounding rock sustains irreparable damage accumulation. For safe tunnel construction, it is imperative to understand the characteristics of blasting dynamic cumulative rock damage. Sonic wave test and numerical simulation methods were applied to the research. The JH-2 model was adopted as the damage model of surrounding rock. Based on the data transfer method between solvers in ABAQUS software, the cumulative damage was calculated. The damage characteristics were obtained by combining the sonic wave test results. According to the research findings, the entire reserved surrounding rock has periodic damage characteristics. Each periodic damage area has a funnel shape along the tunnel’s longitudinal direction, with a length of 160 cm, and 1.07 times the excavation footage. The latter excavation footage's blasting effect on the damaged area of the previous footage rock is 40 cm long, with three cumulative damage patterns. The three cumulative damage patterns more clearly reveal the surrounding rock's additional damage law, the degree of additional damage is greatest with the distance of 5–20 cm from the latter excavation footage. The research can provide appropriate theoretical guidance for the design of the step-blasting construction tunnel's blasting scheme and lining.
Post-GWAS screening of candidate genes for refractive error in mutant zebrafish models
Authors: Quint Wim H. , Tadema Kirke C. D. , Kokke Nina C. C. J. , Meester-Smoor Magda A. , Miller Adam C. , Willemsen Rob , Klaver Caroline C. W. , Iglesias Adriana I. 
Published: February 2023

AbstractGenome-wide association studies (GWAS) have dissected numerous genetic factors underlying refractive errors (RE) such as myopia. Despite significant insights into understanding the genetic architecture of RE, few studies have validated and explored the functional role of candidate genes within these loci. To functionally follow-up on GWAS and characterize the potential role of candidate genes on the development of RE, we prioritized nine genes (TJP2, PDE11A, SHISA6, LAMA2, LRRC4C, KCNQ5, GNB3, RBFOX1, and GRIA4) based on biological and statistical evidence; and used CRISPR/cas9 to generate knock-out zebrafish mutants. These mutant fish were screened for abnormalities in axial length by spectral-domain optical coherence tomography and refractive status by eccentric photorefraction at the juvenile (2 months) and adult (4 months) developmental stage. We found a significantly increased axial length and myopic shift in refractive status in three of our studied mutants, indicating a potential involvement of the human orthologs (LAMA2, LRRC4C, and KCNQ5) in myopia development. Further, in-situ hybridization studies showed that all three genes are expressed throughout the zebrafish retina. Our zebrafish models provide evidence of a functional role of these three genes in refractive error development and offer opportunities to elucidate pathways driving the retina-to-sclera signaling cascade that leads to myopia.
The impact of oxygen supply and erythrocytes during normothermic kidney perfusion
Authors: von Horn Charlotte , Zlatev Hristo , Lüer Bastian , Malkus Laura , Ting Saskia , Minor Thomas 
Published: February 2023

AbstractThe influence of erythrocytes and oxygen concentration on kidneys during long-term normothermic kidney perfusion is under debate. This study compares acellular and erythrocyte-based NMP with focus on oxygen delivery to the tissue as well as the effects of high oxygenation on tissue integrity. Pig kidneys were connected to NMP for six hours. The first group (n = 6; AC500) was perfused without addition of oxygen carriers, arterial perfusate pO2 was maintained at 500 mmHg. In the second group (n = 6; RBC500) washed erythrocytes were added to the perfusate at pO2 of 500 mmHg. Third group (n = 6; RBC200) was perfused with erythrocyte containing perfusate at more physiological pO2 of 200 mmHg. Addition of RBC did not relevantly increase oxygen consumption of the kidneys during perfusion. Likewise, there were no differences in kidney functional and injury parameters between AC500 and RBC500 group. Expression of erythropoietin as indicator of tissue hypoxia was comparable in all three groups. Cell free NMP at supraphysiological oxygen partial pressure seems to be a safe alternative to erythrocyte based perfusion without adverse effect on kidney integrity and provides a less cumbersome application of NMP in clinical practice.
Intrasexual cuticular hydrocarbon dimorphism in a wasp sheds light on hydrocarbon biosynthesis genes in Hymenoptera
Authors: Moris Victoria C. , Podsiadlowski Lars , Martin Sebastian , Oeyen Jan Philip , Donath Alexander , Petersen Malte , Wilbrandt Jeanne , Misof Bernhard , Liedtke Daniel , Thamm Markus , Scheiner Ricarda , Schmitt Thomas , Niehuis Oliver 
Published: February 2023

AbstractCuticular hydrocarbons (CHCs) cover the cuticle of insects and serve as desiccation barrier and as semiochemicals. While the main enzymatic steps of CHC biosynthesis are well understood, few of the underlying genes have been identified. Here we show how exploitation of intrasexual CHC dimorphism in a mason wasp, Odynerus spinipes, in combination with whole-genome sequencing and comparative transcriptomics facilitated identification of such genes. RNAi-mediated knockdown of twelve candidate gene orthologs in the honey bee, Apis mellifera, confirmed nine genes impacting CHC profile composition. Most of them have predicted functions consistent with current knowledge of CHC metabolism. However, we found first-time evidence for a fatty acid amide hydrolase also influencing CHC profile composition. In situ hybridization experiments furthermore suggest trophocytes participating in CHC biosynthesis. Our results set the base for experimental CHC profile manipulation in Hymenoptera and imply that the evolutionary origin of CHC biosynthesis predates the arthropods’ colonization of land.
Three-dimensional mapping in multi-samples with large-scale imaging and multiplexed post staining
Authors: Chen Siqi , Liu Guangcai , Li Anan , Liu Zhixiang , Long Ben , Yang Xiaoquan , Gong Hui , Li Xiangning 
Published: February 2023

AbstractDissection of the anatomical information at the single-cell level is crucial for understanding the organization rule and pathological mechanism of biological tissues. Mapping the whole organ in numerous groups with multiple conditions brings the challenges in imaging and analysis. Here, we describe an approach, named array fluorescent micro-optical sectioning tomography (array-fMOST), to identify the three-dimensional information at single-cell resolution from multi-samples. The pipeline contains array embedding, large-scale imaging, post-imaging staining and data analysis, which could image over 24 mouse brains simultaneously and collect the slices for further analysis. With transgenic mice, we acquired the distribution information of neuropeptide somatostatin neurons during natural aging and compared the changes in the microenvironments by multi-component labeling of serial sections with precise co-registration of serial datasets quantitatively. With viral labeling, we also analyzed the input circuits of the medial prefrontal cortex in the whole brain of Alzheimer’s disease and autism model mice. This pipeline is highly scalable to be applied to anatomical alterations screening and identification. It provides new opportunities for combining multi-sample whole-organ imaging and molecular phenotypes identification analysis together. Such integrated high-dimensional information acquisition method may accelerate our understanding of pathogenesis and progression of disease in situ at multiple levels.
Genome-wide association study reveals BET1L associated with survival time in the 137,693 Japanese individuals
Authors: Akiyama Masato , Sakaue Saori , Takahashi Atsushi , Ishigaki Kazuyoshi , Hirata Makoto , Matsuda Koichi , Momozawa Yukihide , Okada Yukinori , Ninomiya Toshiharu ,   The Biobank Japan project, Koido Masaru , Morisaki Takayuki , Nagai Akiko , Sagiya Yoji , Terao Chikashi , Murakami Yoshinori , Kubo Michiaki , Kamatani Yoichiro 
Published: February 2023

AbstractHuman lifespan is reported to be heritable. Although previous genome-wide association studies (GWASs) have identified several loci, a limited number of studies have assessed the genetic associations with the real survival information on the participants. We conducted a GWAS to identify loci associated with survival time in the Japanese individuals participated in the BioBank Japan Project by carrying out sex-stratified GWASs involving 78,029 males and 59,664 females. Of them, 31,324 (22.7%) died during the mean follow-up period of 7.44 years. We found a novel locus associated with survival (BET1L; P = 5.89 × 10−9). By integrating with eQTL data, we detected a significant overlap with eQTL of BET1L in skeletal muscle. A gene-set enrichment analysis showed that genes related to the BCAR1 protein–protein interaction subnetwork influence survival time (P = 1.54 × 10−7). These findings offer the candidate genes and biological mechanisms associated with human lifespan.
Life on a beach leads to phenotypic divergence despite gene flow for an island lizard
Authors: Brown Richard P. , Jin Yuanting , Thomas Jordan , Meloro Carlo 
Published: February 2023

AbstractLimited spatial separation within small islands suggests that observed population divergence may occur due to habitat differences without interruption to gene flow but strong evidence of this is scarce. The wall lizard Teira dugesii lives in starkly contrasting shingle beach and inland habitats on the island of Madeira. We used a matched pairs sampling design to examine morphological and genomic divergence between four beach and adjacent (<1 km) inland areas. Beach populations are significantly darker than corresponding inland populations. Geometric morphometric analyses reveal divergence in head morphology: beach lizards have generally wider snouts. Genotyping-by-sequencing allows the rejection of the hypothesis that beach populations form a distinct lineage. Bayesian analyses provide strong support for models that incorporate gene flow, relative to those that do not, replicated at all pairs of matched sites. Madeiran lizards show morphological divergence between habitats in the face of gene flow, revealing how divergence may originate within small islands.
On the interplay between lipids and asymmetric dynamics of an NBS degenerate ABC transporter
Authors: Tóth Ágota , Janaszkiewicz Angelika , Crespi Veronica , Di Meo Florent 
Published: February 2023

AbstractMultidrug resistance-associated proteins are ABC C-family exporters. They are crucial in pharmacology as they transport various substrates across membranes. However, the role of the degenerate nucleotide-binding site (NBS) remains unclear likewise the interplay with the surrounding lipid environment. Here, we propose a dynamic and structural overview of MRP1 from ca. 110 μs molecular dynamics simulations. ATP binding to NBS1 is likely maintained along several transport cycles. Asymmetric NBD behaviour is ensured by lower signal transduction from NBD1 to the rest of the protein owing to the absence of ball-and-socket conformation between NBD1 and coupling helices. Even though surrounding lipids play an active role in the allosteric communication between the substrate-binding pocket and NBDs, our results suggest that lipid composition has a limited impact, mostly by affecting transport kinetics. We believe that our work can be extended to other degenerate NBS ABC proteins and provide hints for deciphering mechanistic differences among ABC transporters.
Role of optical rectification in photon-assisted tunneling current
Authors: Février Pierre , Basset Julien , Estève Jérôme , Aprili Marco , Gabelli Julien 
Published: February 2023

AbstractEmission of light and conversely rectification of an optical signal using an all-metallic electronic device is of fundamental and technological importance for nano-optics. However despite recent experimental efforts in the development of electrically-driven plasmonic sources, the interplay between quantum transport and optics is still under debate. Here, we measure the photon-assisted current in a planar tunnel junction under infrared illumination. To address the microscopic mechanism at the origin of the optical rectification, we compare the photon-assisted current and the current-voltage characteristic of the junction measured on a voltage range much greater than $${V}_{0}=\frac{hc}{e\lambda }=0.825\,{{{{{{{\rm{V}}}}}}}}$$

V

0

=

h
c

e
λ

=
0.825

V
, previously unexplored. The experimental results do not agree with the theory based on the existence of a non-thermal distribution function corresponding to the exchange of energy quanta between electrons and photons. We show instead that the illumination power mainly goes into heating and that the rectification results from the tunneling Seebeck effect.
High-entropy grain boundaries
Authors: Luo Jian , Zhou Naixie 
Published: February 2023

AbstractAs high-entropy alloys receive an increasing amount of attention, an interesting scientific question arises: can grain boundaries be “high entropy”? In 2016, we proposed “high-entropy grain boundaries” as the grain boundary counterparts to high-entropy materials. Here, we discuss the underlying interfacial thermodynamics to elaborate relevant concepts. We emphasize that “high-entropy grain boundaries” are neither equivalent to grain boundaries in high-entropy materials nor simply “compositionally complex grain boundaries”, but they should possess specific thermodynamic characters. Using a simplified segregation model, we illustrate that both grain boundary and bulk high-entropy effects can reduce grain boundary energy with increasing temperature for saturated multicomponent alloys, where the effective grain boundary entropy can be positive and increase with the number of components. We show that high-entropy grain boundaries can stabilize nanocrystalline alloys at high temperatures via thermodynamic and kinetic effects. Grain boundary structural disordering and transitions may offer further opportunities to attain higher effective grain boundary entropies.
Projected decrease in trail access in the Arctic
Authors: Ford J. D. , Clark D. G. , Copland L. , Pearce T. ,   IHACC Research Team, Ford James D. , Harper Sherilee , Ford Lea Berrang , Carcamo Cesar , Garcia Patricia , Lwasa Shuaib , Namanya Didacus , New Mark , Zavaleta-Cortijo Carol , Harper S. L. 
Published: February 2023

AbstractTransportation systems in northern Canada are highly sensitive to climate change. We project how access to semi-permanent trails on land, water, and sea ice might change this century in Inuit Nunangat (the Inuit homeland in northern Canada), using CMIP6 projections coupled with trail access models developed with community members. Overall trail access is projected to diminish, with large declines in access for sea ice trails which play a central role for Inuit livelihoods and culture; limits to adaptation in southern regions of Inuit Nunangat within the next 40 years; a lengthening of the period when no trails are accessible; and an unequal distribution of impacts according to the knowledge, skills, equipment, and risk tolerance of trail users. There are opportunities for adaptation through efforts to develop skillsets and confidence in travelling in more marginal environmental conditions, which can considerably extend the envelope of days when trails are accessible and months when this is possible. Such actions could reduce impacts across emissions scenarios but their potential effectiveness declines at higher levels of global warming, and in southern regions only delays when sea ice trails become unusable.