bluuebunny/crossref_metadata_2025 huggingface dataset:
Extravillous trophoblast cell lineage development is associated with active remodeling of the chromatin landscape
Authors: Varberg Kaela M. , Dominguez Esteban M. , Koseva Boryana , Varberg Joseph M. , McNally Ross P. , Moreno-Irusta Ayelen , Wesley Emily R. , Iqbal Khursheed , Cheung Warren A. , Schwendinger-Schreck Carl , Smail Craig , Okae Hiroaki , Arima Takahiro , Lydic Michael , Holoch Kristin , Marsh Courtney , Soares Michael J. , Grundberg Elin
Published: August 2023

The extravillous trophoblast cell lineage is a key feature of placentation and successful pregnancy. Knowledge of transcriptional regulation driving extravillous trophoblast cell development is limited. Here, we map the transcriptome and epigenome landscape as well as chromatin interactions of human trophoblast stem cells and their transition into extravillous trophoblast cells. We show that integrating chromatin accessibility, long-range chromatin interactions, transcriptomic, and transcription factor binding motif enrichment enables identification of transcription factors and regulatory mechanisms critical for extravillous trophoblast cell development. We elucidate functional roles for TFAP2C, SNAI1, and EPAS1 in the regulation of extravillous trophoblast cell development. EPAS1 is identified as an upstream regulator of key extravillous trophoblast cell transcription factors, including ASCL2 and SNAI1 and together with its target genes, is linked to pregnancy loss and birth weight. Collectively, we reveal activation of a dynamic regulatory network and provide a framework for understanding extravillous trophoblast cell specification in trophoblast cell lineage development and human placentation.
Indian Ocean glacial deoxygenation and respired carbon accumulation during mid-late Quaternary ice ages
Authors: Chang Liao , Hoogakker Babette A. A. , Heslop David , Zhao Xiang , Roberts Andrew P. , De Deckker Patrick , Xue Pengfei , Pei Zhaowen , Zeng Fan , Huang Rong , Huang Baoqi , Wang Shishun , Berndt Thomas A. , Leng Melanie , Stuut Jan-Berend W. , Harrison Richard J.
Published: August 2023

Reconstructions of ocean oxygenation are critical for understanding the role of respired carbon storage in regulating atmospheric CO2. Independent sediment redox proxies are essential to assess such reconstructions. Here, we present a long magnetofossil record from the eastern Indian Ocean in which we observe coeval magnetic hardening and enrichment of larger, more elongated, and less oxidized magnetofossils during glacials compared to interglacials over the last ~900 ka. Our multi-proxy records of redox-sensitive magnetofossils, trace element concentrations, and benthic foraminiferal Δδ13C consistently suggest a recurrence of lower O2 in the glacial Indian Ocean over the last 21 marine isotope stages, as has been reported for the Atlantic and Pacific across the last glaciation. Consistent multi-proxy documentation of this repeated oxygen decline strongly supports the hypothesis that increased Indian Ocean glacial carbon storage played a significant role in atmospheric CO2 cycling and climate change over recent glacial/interglacial timescales.
Applied machine learning as a driver for polymeric biomaterials design
Authors: McDonald Samantha M. , Augustine Emily K. , Lanners Quinn , Rudin Cynthia , Catherine Brinson L. , Becker Matthew L.
Published: August 2023

Polymers are ubiquitous to almost every aspect of modern society and their use in medical products is similarly pervasive. Despite this, the diversity in commercial polymers used in medicine is stunningly low. Considerable time and resources have been extended over the years towards the development of new polymeric biomaterials which address unmet needs left by the current generation of medical-grade polymers. Machine learning (ML) presents an unprecedented opportunity in this field to bypass the need for trial-and-error synthesis, thus reducing the time and resources invested into new discoveries critical for advancing medical treatments. Current efforts pioneering applied ML in polymer design have employed combinatorial and high throughput experimental design to address data availability concerns. However, the lack of available and standardized characterization of parameters relevant to medicine, including degradation time and biocompatibility, represents a nearly insurmountable obstacle to ML-aided design of biomaterials. Herein, we identify a gap at the intersection of applied ML and biomedical polymer design, highlight current works at this junction more broadly and provide an outlook on challenges and future directions.
Photoredox cobalt-catalyzed regio-, diastereo- and enantioselective propargylation of aldehydes via propargyl radicals
Authors: Wang Lei , Lin Chuiyi , Chong Qinglei , Zhang Zhihan , Meng Fanke
Published: August 2023

Catalytic enantioselective introduction of a propargyl group constitutes one of the most important carbon–carbon forming reactions, as it is versatile to be transformed into diverse functional groups and frequently used in the synthesis of natural products and biologically active molecules. Stereoconvergent transformations of racemic propargyl precursors to a single enantiomer of products via propargyl radicals represent a powerful strategy and provide new reactivity. However, only few Cu- or Ni-catalyzed protocols have been developed with limited reaction modes. Herein, a photoredox/cobalt-catalyzed regio-, diastereo- and enantioselective propargyl addition to aldehydes via propargyl radicals is presented, enabling construction of a broad scope of homopropargyl alcohols that are otherwise difficult to access in high efficiency and stereoselectivity from racemic propargyl carbonates. Mechanistic studies and DFT calculations provided evidence for the involvement of propargyl radicals, the origin of the stereoconvergent process and the stereochemical models.
Machine learning assisted quantum super-resolution microscopy
Authors: Kudyshev Zhaxylyk A. , Sychev Demid , Martin Zachariah , Yesilyurt Omer , Bogdanov Simeon I. , Xu Xiaohui , Chen Pei-Gang , Kildishev Alexander V. , Boltasseva Alexandra , Shalaev Vladimir M.
Published: August 2023

One of the main characteristics of optical imaging systems is spatial resolution, which is restricted by the diffraction limit to approximately half the wavelength of the incident light. Along with the recently developed classical super-resolution techniques, which aim at breaking the diffraction limit in classical systems, there is a class of quantum super-resolution techniques which leverage the non-classical nature of the optical signals radiated by quantum emitters, the so-called antibunching super-resolution microscopy. This approach can ensure a factor of $$\sqrt{n}$$

n

improvement in the spatial resolution by measuring the n -th order autocorrelation function. The main bottleneck of the antibunching super-resolution microscopy is the time-consuming acquisition of multi-photon event histograms. We present a machine learning-assisted approach for the realization of rapid antibunching super-resolution imaging and demonstrate 12 times speed-up compared to conventional, fitting-based autocorrelation measurements. The developed framework paves the way to the practical realization of scalable quantum super-resolution imaging devices that can be compatible with various types of quantum emitters.
Genomic epidemiology offers high resolution estimates of serial intervals for COVID-19
Authors: Stockdale Jessica E. , Susvitasari Kurnia , Tupper Paul , Sobkowiak Benjamin , Mulberry Nicola , Gonçalves da Silva Anders , Watt Anne E. , Sherry Norelle L. , Minko Corinna , Howden Benjamin P. , Lane Courtney R. , Colijn Caroline
Published: August 2023

Serial intervals – the time between symptom onset in infector and infectee – are a fundamental quantity in infectious disease control. However, their estimation requires knowledge of individuals’ exposures, typically obtained through resource-intensive contact tracing efforts. We introduce an alternate framework using virus sequences to inform who infected whom and thereby estimate serial intervals. We apply our technique to SARS-CoV-2 sequences from case clusters in the first two COVID-19 waves in Victoria, Australia. We find that our approach offers high resolution, cluster-specific serial interval estimates that are comparable with those obtained from contact data, despite requiring no knowledge of who infected whom and relying on incompletely-sampled data. Compared to a published serial interval, cluster-specific serial intervals can vary estimates of the effective reproduction number by a factor of 2–3. We find that serial interval estimates in settings such as schools and meat processing/packing plants are shorter than those in healthcare facilities.
Concerning the stability of seawater electrolysis: a corrosion mechanism study of halide on Ni-based anode
Authors: Zhang Sixie , Wang Yunan , Li Shuyu , Wang Zhongfeng , Chen Haocheng , Yi Li , Chen Xu , Yang Qihao , Xu Wenwen , Wang Aiying , Lu Zhiyi
Published: August 2023

The corrosive anions (e.g., Cl−) have been recognized as the origins to cause severe corrosion of anode during seawater electrolysis, while in experiments it is found that natural seawater (~0.41 M Cl−) is usually more corrosive than simulated seawater (~0.5 M Cl−). Here we elucidate that besides Cl−, Br− in seawater is even more harmful to Ni-based anodes because of the inferior corrosion resistance and faster corrosion kinetics in bromide than in chloride. Experimental and simulated results reveal that Cl− corrodes locally to form narrow-deep pits while Br− etches extensively to generate shallow-wide pits, which can be attributed to the fast diffusion kinetics of Cl− and the lower reaction energy of Br− in the passivation layer. Additionally, for the Ni-based electrodes with catalysts (e.g., NiFe-LDH) loading on the surface, Br− causes extensive spalling of the catalyst layer, resulting in rapid performance degradation. This work clearly points out that, in addition to anti-Cl− corrosion, designing anti-Br− corrosion anodes is even more crucial for future application of seawater electrolysis.
Polyelectrolyte elastomer-based ionotronic sensors with multi-mode sensing capabilities via multi-material 3D printing
Authors: Li Caicong , Cheng Jianxiang , He Yunfeng , He Xiangnan , Xu Ziyi , Ge Qi , Yang Canhui
Published: August 2023

Stretchable ionotronics have drawn increasing attention during the past decade, enabling myriad applications in engineering and biomedicine. However, existing ionotronic sensors suffer from limited sensing capabilities due to simple device structures and poor stability due to the leakage of ingredients. In this study, we rationally design and fabricate a plethora of architected leakage-free ionotronic sensors with multi-mode sensing capabilities, using DLP-based 3D printing and a polyelectrolyte elastomer. We synthesize a photo-polymerizable ionic monomer for the polyelectrolyte elastomer, which is stretchable, transparent, ionically conductive, thermally stable, and leakage-resistant. The printed sensors possess robust interfaces and extraordinary long-term stability. The multi-material 3D printing allows high flexibility in structural design, enabling the sensing of tension, compression, shear, and torsion, with on-demand tailorable sensitivities through elaborate programming of device architectures. Furthermore, we fabricate integrated ionotronic sensors that can perceive different mechanical stimuli simultaneously without mutual signal interferences. We demonstrate a sensing kit consisting of four shear sensors and one compressive sensor, and connect it to a remote-control system that is programmed to wirelessly control the flight of a drone. Multi-material 3D printing of leakage-free polyelectrolyte elastomers paves new avenues for manufacturing stretchable ionotronics by resolving the deficiencies of stability and functionalities simultaneously.
Direct sulfuric acid formation from the gas-phase oxidation of reduced-sulfur compounds
Authors: Berndt Torsten , Hoffmann Erik H. , Tilgner Andreas , Stratmann Frank , Herrmann Hartmut
Published: August 2023

Sulfuric acid represents a fundamental precursor for new nanometre-sized atmospheric aerosol particles. These particles, after subsequent growth, may influence Earth´s radiative forcing directly, or indirectly through affecting the microphysical and radiative properties of clouds. Currently considered formation routes yielding sulfuric acid in the atmosphere are the gas-phase oxidation of SO2 initiated by OH radicals and by Criegee intermediates, the latter being of little relevance. Here we report the observation of immediate sulfuric acid production from the OH reaction of emitted organic reduced-sulfur compounds, which was speculated about in the literature for decades. Key intermediates are the methylsulfonyl radical, CH3SO2, and, even more interestingly, its corresponding peroxy compound, CH3SO2OO. Results of modelling for pristine marine conditions show that oxidation of reduced-sulfur compounds could be responsible for up to ∼50% of formed gas-phase sulfuric acid in these areas. Our findings provide a more complete understanding of the atmospheric reduced-sulfur oxidation.
Universal radiation tolerant semiconductor
Authors: Azarov Alexander , Fernández Javier García , Zhao Junlei , Djurabekova Flyura , He Huan , He Ru , Prytz Øystein , Vines Lasse , Bektas Umutcan , Chekhonin Paul , Klingner Nico , Hlawacek Gregor , Kuznetsov Andrej
Published: August 2023

Radiation tolerance is determined as the ability of crystalline materials to withstand the accumulation of the radiation induced disorder. Nevertheless, for sufficiently high fluences, in all by far known semiconductors it ends up with either very high disorder levels or amorphization. Here we show that gamma/beta (γ/β) double polymorph Ga2O3 structures exhibit remarkably high radiation tolerance. Specifically, for room temperature experiments, they tolerate a disorder equivalent to hundreds of displacements per atom, without severe degradations of crystallinity; in comparison with, e.g., Si amorphizable already with the lattice atoms displaced just once. We explain this behavior by an interesting combination of the Ga- and O- sublattice properties in γ-Ga2O3. In particular, O-sublattice exhibits a strong recrystallization trend to recover the face-centered-cubic stacking despite the stronger displacement of O atoms compared to Ga during the active periods of cascades. Notably, we also explained the origin of the β-to-γ Ga2O3 transformation, as a function of the increased disorder in β-Ga2O3 and studied the phenomena as a function of the chemical nature of the implanted atoms. As a result, we conclude that γ/β double polymorph Ga2O3 structures, in terms of their radiation tolerance properties, benchmark a class of universal radiation tolerant semiconductors.
Imaging the dynamic influence of functional groups on metal-organic frameworks
Authors: Liu Boyang , Chen Xiao , Huang Ning , Liu Shaoxiong , Wang Yu , Lan Xiaocheng , Wei Fei , Wang Tiefeng
Published: August 2023

Metal-organic frameworks (MOFs) with different functional groups have wide applications, while the understanding of functionalization influences remains insufficient. Previous researches focused on the static changes in electronic structure or chemical environment, while it is unclear in the aspect of dynamic influence, especially in the direct imaging of dynamic changes after functionalization. Here we use integrated differential phase contrast scanning transmission electron microscopy (iDPC-STEM) to directly ‘see’ the rotation properties of benzene rings in the linkers of UiO-66, and observe the high correlation between local rigidity and the functional groups on the organic linkers. The rigidity is then correlated to the macroscopic properties of CO2 uptake, indicating that functionalization can change the capability through not only static electronic effects, but also dynamic rotation properties. To the best of our knowledge this is the first example of a technique to directly image the rotation properties of linkers in MOFs, which provides an approach to study the local flexibility and paves the way for potential applications in capturing, separation and molecular machine.
Revealing low-loss dielectric near-field modes of hexagonal boron nitride by photoemission electron microscopy
Authors: Li Yaolong , Jiang Pengzuo , Lyu Xiaying , Li Xiaofang , Qi Huixin , Tang Jinglin , Xue Zhaohang , Yang Hong , Lu Guowei , Sun Quan , Hu Xiaoyong , Gao Yunan , Gong Qihuang
Published: August 2023

Low-loss dielectric modes are important features and functional bases of fundamental optical components in on-chip optical devices. However, dielectric near-field modes are challenging to reveal with high spatiotemporal resolution and fast direct imaging. Herein, we present a method to address this issue by applying time-resolved photoemission electron microscopy to a low-dimensional wide-bandgap semiconductor, hexagonal boron nitride (hBN). Taking a low-loss dielectric planar waveguide as a fundamental structure, static vector near-field vortices with different topological charges and the spatiotemporal evolution of waveguide modes are directly revealed. With the lowest-order vortex structure, strong nanofocusing in real space is realized, while near-vertical photoemission in momentum space and narrow spread in energy space are simultaneously observed due to the atomically flat surface of hBN and the small photoemission horizon set by the limited photon energies. Our approach provides a strategy for the realization of flat photoemission emitters.
Access to unsaturated bicyclic lactones by overriding conventional C(sp3)–H site selectivity
Authors: Das Jayabrata , Ali Wajid , Ghosh Animesh , Pal Tanay , Mandal Astam , Teja Chitrala , Dutta Suparna , Pothikumar Rajagopal , Ge Haibo , Zhang Xinglong , Maiti Debabrata
Published: August 2023

Transition metal catalysis plays a pivotal role in transforming unreactive C–H bonds. However, regioselective activation of distal aliphatic C–H bonds poses a tremendous challenge, particularly in the absence of directing templates. Activation of a methylene C–H bond in the presence of methyl C–H is underexplored. Here we show activation of a methylene C–H bond in the presence of methyl C–H bonds to form unsaturated bicyclic lactones. The protocol allows the reversal of the general selectivity in aliphatic C–H bond activation. Computational studies suggest that reversible C–H activation is followed by β-hydride elimination to generate the Pd-coordinated cycloalkene that undergoes stereoselective C–O cyclization, and subsequent β-hydride elimination to provide bicyclic unsaturated lactones. The broad generality of this reaction has been highlighted via dehydrogenative lactonization of mid to macro ring containing acids along with the C–H olefination reaction with olefin and allyl alcohol. The method substantially simplifies the synthesis of important bicyclic lactones that are important features of natural products as well as pharmacoactive molecules.
Geometrical digital twins of the as-built microstructure of three-leaf stone masonry walls with laser scanning
Authors: Saloustros Savvas , Settimi Andrea , Ascencio Andrea Cabriada , Gamerro Julien , Weinand Yves , Beyer Katrin
Published: August 2023

Research on irregular stone masonry walls is hampered by the lack of detailed geometrical models of their internal micro-structure, i.e. the shape and size of each stone and its position within the wall. Without such a geometric digital twin of walls tested in the laboratory, it is difficult to evaluate the accuracy of existing numerical simulation techniques. Here, we describe the generation of geometrical digital twins of three irregular stone masonry walls built in the laboratory. We labelled each stone manually and then obtained the geometry of the individual stones using a portable laser scanning device. With the same device we scanned the wall after the construction of each layer. We then registered the position of each stone in the layer. This paper outlines the methodology for the data acquisition and digital reconstruction and presents the datasets for the walls. The developed geometrical digital twins provide unique information regarding the micro-structure of constructed walls that is key for the development and validation of numerical simulation techniques for stone masonry.
Unraveling the whole genome DNA methylation profile of zebrafish kidney marrow by Oxford Nanopore sequencing
Authors: Liu Xudong , Ni Ying , Wang Dandan , Ye Silin , Yang Mengsu , Sun Xuan , Leung Anskar Yu Hung , Li Runsheng
Published: August 2023

Zebrafish is a widely used model organism for investigating human diseases, including hematopoietic disorders. However, a comprehensive methylation baseline for zebrafish primary hematopoietic organ, the kidney marrow (KM), is still lacking. We employed Oxford Nanopore Technologies (ONT) sequencing to profile DNA methylation in zebrafish KM by generating four KM datasets, with two groups based on the presence or absence of red blood cells. Our findings revealed that blood contamination in the KM samples reduced read quality and altered methylation patterns. Compared with whole-genome bisulfite sequencing (WGBS), the ONT-based methylation profiling can cover more CpG sites (92.4% vs 70%–80%), and exhibit less GC bias with more even genomic coverage. And the ONT methylation calling results showed a high correlation with WGBS results when using shared sites. This study establishes a comprehensive methylation profile for zebrafish KM, paving the way for further investigations into epigenetic regulation and the development of targeted therapies for hematopoietic disorders.
High-quality wild barley genome assemblies and annotation with Nanopore long reads and Hi-C sequencing data
Authors: Pan Rui , Hu Haifei , Xiao Yuhui , Xu Le , Xu Yanhao , Ouyang Kai , Li Chengdao , He Tianhua , Zhang Wenying
Published: August 2023

Wild barley, from “Evolution Canyon (EC)” in Mount Carmel, Israel, are ideal models for cereal chromosome evolution studies. Here, the wild barley EC_S1 is from the south slope with higher daily temperatures and drought, while EC_N1 is from the north slope with a cooler climate and higher relative humidity, which results in a differentiated selection due to contrasting environments. We assembled a 5.03 Gb genome with contig N50 of 3.53 Mb for wild barley EC_S1 and a 5.05 Gb genome with contig N50 of 3.45 Mb for EC_N1 using 145 Gb and 160.0 Gb Illumina sequencing data, 295.6 Gb and 285.35 Gb Nanopore sequencing data and 555.1 Gb and 514.5 Gb Hi-C sequencing data, respectively. BUSCOs and CEGMA evaluation suggested highly complete assemblies. Using full-length transcriptome data, we predicted 39,179 and 38,373 high-confidence genes in EC_S1 and EC_N1, in which 93.6% and 95.2% were functionally annotated, respectively. We annotated repetitive elements and non-coding RNAs. These two wild barley genome assemblies will provide a rich gene pool for domesticated barley.
An improved PBFT consensus algorithm based on grouping and credit grading
Authors: Liu Shannan , Zhang Ronghua , Liu Changzheng , Xu Chenxi , Wang Jiaojiao
Published: August 2023

To improve the blockchain consensus algorithm practical Byzantine fault tolerance (PBFT) with random master node selection, which has high communication overhead and a small supported network size, this paper proposes a Byzantine fault tolerant consensus algorithm based on credit (CBFT) enhanced with a grouping and credit model. The CBFT algorithm divides the network nodes according to the speed of their response to the management nodes, resulting in different consensus sets, and achieves consensus within and outside the group separately to reduce communication overhead and increase system security. Second, the nodes are divided into different types according to the credit model, each with different responsibilities to reduce the probability that the master node is a malicious node. Experimental results show that the throughput of the CBFT algorithm is 3.1 times that of PBFT and 1.5 times that of GPBFT when the number of nodes is 52. Our scheme has latency that is 7.4% that of PBFT and 38.8% that of GPBFT; CBFT has communication overhead that is 6.4% that of PBFT and 87.3% that of GPBFT. The number of nodes is 300, and the Byzantine fault tolerance is improved by 59.3%. These improvements are clearer with the increase in the number of nodes.
Development of a spore-based mucosal vaccine against the bovine respiratory pathogen Mannheimia haemolytica
Authors: Uddin Muhammed Salah , Guluarte Jose Ortiz , Abbott D. Wade , Inglis G. Douglas , Guan Le Luo , Alexander Trevor W.
Published: August 2023

Bovine respiratory disease (BRD) is a significant health issue in the North American feedlot industry, causing substantial financial losses due to morbidity and mortality. A lack of effective vaccines against BRD pathogens has resulted in antibiotics primarily being used for BRD prevention. The aim of this study was to develop a mucosal vaccine against the BRD pathogen, Mannheimia haemolytica, using Bacillus subtilis spores as an adjuvant. A chimeric protein (MhCP) containing a tandem repeat of neutralizing epitopes from M. haemolytica leukotoxin A (NLKT) and outer membrane protein PlpE was expressed to produce antigen for adsorption to B. subtilis spores. Adsorption was optimized by comparing varying amounts of antigen and spores, as well as different buffer pH and reaction temperatures. Using the optimal adsorption parameters, spore-bound antigen (Spore-MhCP) was prepared and administered to mice via two mucosal routes (intranasal and intragastric), while intramuscular administration of free MhCP and unvaccinated mice were used as positive and negative control treatments, respectively. Intramuscular administration of MhCP elicited the strongest serum IgG response. However, intranasal immunization of Spore-MhCP generated the best secretory IgA-specific response against both PlpE and NLKT in all samples evaluated (bronchoalveolar lavage, saliva, and feces). Since proliferation of M. haemolytica in the respiratory tract is a prerequisite to lung infection, this spore-based vaccine may offer protection in cattle by limiting colonization and subsequent infection, and Spore-MhCP warrants further evaluation in cattle as a mucosal vaccine against M. haemolytica.
Efficacy of microbicidal actives and formulations for inactivation of Lassa virus in suspension
Authors: Cutts Todd A. , Nims Raymond W. , Rubino Joseph R. , McKinney Julie , Kuhn Jens H. , Ijaz M. Khalid
Published: August 2023

The World Health Organization’s R&D Blueprint list of priority diseases for 2022 includes Lassa fever, signifying the need for research and development in emergency contexts. This disease is caused by the arenavirus Lassa virus (LASV). Being an enveloped virus, LASV should be susceptible to a variety of microbicidal actives, although empirical data to support this expectation are needed. We evaluated the virucidal efficacy of sodium hypochlorite, ethanol, a formulated dual quaternary ammonium compound, an accelerated hydrogen peroxide formulation, and a p-chloro-m-xylenol formulation, per ASTM E1052-20, against LASV engineered to express green fluorescent protein (GFP). A 10-μL volume of virus in tripartite soil (bovine serum albumin, tryptone, and mucin) was combined with 50 μL of disinfectant in suspension for 0.5, 1, 5, or 10 min at 20–25 °C. Neutralized test mixtures were quantified by GFP expression to determine log10 reduction. Remaining material was passaged on Vero cells to confirm absence of residual infectious virus. Input virus titers of 6.6–8.0 log10 per assay were completely inactivated by each disinfectant within 1–5 min contact time. The rapid and substantial inactivation of LASV suggests the utility of these microbicides for mitigating spread of infectious virus during Lassa fever outbreaks.
Mapping robust multiscale communities in chromosome contact networks
Authors: Holmgren Anton , Bernenko Dolores , Lizana Ludvig
Published: August 2023

To better understand DNA’s 3D folding in cell nuclei, researchers developed chromosome capture methods such as Hi-C that measure the contact frequencies between all DNA segment pairs across the genome. As Hi-C data sets often are massive, it is common to use bioinformatics methods to group DNA segments into 3D regions with correlated contact patterns, such as Topologically associated domains and A/B compartments. Recently, another research direction emerged that treats the Hi-C data as a network of 3D contacts. In this representation, one can use community detection algorithms from complex network theory that group nodes into tightly connected mesoscale communities. However, because Hi-C networks are so densely connected, several node partitions may represent feasible solutions to the community detection problem but are indistinguishable unless including other data. Because this limitation is a fundamental property of the network, this problem persists regardless of the community-finding or data-clustering method. To help remedy this problem, we developed a method that charts the solution landscape of network partitions in Hi-C data from human cells. Our approach allows us to scan seamlessly through the scales of the network and determine regimes where we can expect reliable community structures. We find that some scales are more robust than others and that strong clusters may differ significantly. Our work highlights that finding a robust community structure hinges on thoughtful algorithm design or method cross-evaluation.
Perceived control, loneliness, early-life stress, and parents’ perceptions of stress
Authors: Smith Karen E. , Graf Eileen , Faig Kelly E. , Dimitroff Stephanie J. , Rockwood Frederica , Hernandez Marc W. , Norman Greg J.
Published: August 2023

The COVID-19 pandemic has highlighted the importance of understanding what contributes to individual variability in experiences of stress. Increases in stress related to the pandemic have been especially pronounced in parents, indicating a need for research examining what factors contribute to parents’ perceptions of stress. Here, we assessed the relationship between parents’ perceptions of stress, control, loneliness, and experiences of childhood trauma in two populations of caregivers. In Study 1, we examined the relationship between perceptions of stress, control, loneliness, and history of early stress, along with indices of socioeconomic risk and resting parasympathetic nervous systema activity, which has been linked to variability in perceptions of stress, in caregivers of young children. Perceived control, loneliness, childhood stress, and resting parasympathetic nervous system activity predicted caregivers’ stress. In Study 2, we replicated these initial findings in a second sample of caregivers. Additionally, we examined how these processes change over time. Caregivers demonstrated significant changes in perceptions of control, loneliness, and stress, and changes in control and childhood trauma history were associated with changes in perceptions of stress. Together these results indicate the importance of assessing how caregivers perceive their environment when examining what contributes to increased risk for stress. Additionally, they suggest that caregivers’ stress-related processes are malleable and provide insight into potential targets for interventions aimed at reducing parents’ stress.
Observing Etna volcano dynamics through seismic and deformation patterns
Authors: Scarfì L. , Aloisi M. , Barberi G. , Langer H.
Published: August 2023

Geophysical data provide the chance to investigate a volcano’s dynamics; considerable information can especially be gleaned on the stress and strain patterns accompanying the internal processes and the effect of magma ascent on the main structures triggering earthquakes. Here, we analysed in detail the seismicity recorded over the last two decades on Etna volcano (southern Italy), focusing on earthquakes distribution and focal mechanism clustering; the ground deformation pattern affecting the volcanic edifice with the inflation and deflation phases was also examined. Analysed data were compared in order to shed light on possible relationships with the volcanic activity and to better understand the internal dynamics of the volcano over time. Significant steps during or shortly before major eruptions in the seismic strain release and ground deformation temporal series highlight a straightforward relationship between seismicity occurring at shallow level, inflation/deflation and volcanism. Furthermore, at depths greater than 5–7 km, down to about 20 km, the orientation of the P- and T-axes clearly indicate the existence of a pressure source in the central part of the volcano. All the results underline that the stress field related to the volcano plumbing system interferes with the regional field, partly overriding it.
Streamlined identification of strain engineering targets for bioprocess improvement using metabolic pathway enrichment analysis
Authors: Cortada-Garcia Joan , Daly Rónán , Arnold S. Alison , Burgess Karl
Published: August 2023

Metabolomics is a powerful tool for the identification of genetic targets for bioprocess optimisation. However, in most cases, only the biosynthetic pathway directed to product formation is analysed, limiting the identification of these targets. Some studies have used untargeted metabolomics, allowing a more unbiased approach, but data interpretation using multivariate analysis is usually not straightforward and requires time and effort. Here we show, for the first time, the application of metabolic pathway enrichment analysis using untargeted and targeted metabolomics data to identify genetic targets for bioprocess improvement in a more streamlined way. The analysis of an Escherichia coli succinate production bioprocess with this methodology revealed three significantly modulated pathways during the product formation phase: the pentose phosphate pathway, pantothenate and CoA biosynthesis and ascorbate and aldarate metabolism. From these, the two former pathways are consistent with previous efforts to improve succinate production in Escherichia coli. Furthermore, to the best of our knowledge, ascorbate and aldarate metabolism is a newly identified target that has so far never been explored for improving succinate production in this microorganism. This methodology therefore represents a powerful tool for the streamlined identification of strain engineering targets that can accelerate bioprocess optimisation.
Ultra-deep sequencing of 45S rDNA to discern intragenomic diversity in three Chrysodeixis species for molecular identification
Authors: Zink Frida A. , Tembrock Luke R. , Timm Alicia E. , Gilligan Todd M.
Published: August 2023

Species identification is necessary to prevent introductions of exotic plant pests through global trade. Many of these pests are understudied and lack publicly available DNA sequence data on which rapid molecular identification methods can be based. One such lineage is the genus Chrysodeixis, which includes three species of potential concern for United States trade initiatives: C. includens, C. chalcites, and C. eriosoma. Here we describe a method to generate robust 45S rDNA profiles using long read sequencing in order to clarify evolutionary relationships and develop a real-time PCR identification technique. Such an identification tool will be useful in rapidly differentiating between Chrysodeixis species of quarantine concern where traditional morphological identification methods are insufficient. Molecular methods such as this greatly reduce the time spent identifying each specimen, allow for detection of eDNA, vastly increase throughput, and increase the probability of detection. The methods presented here will be generally adaptable to any understudied lepidopteran taxa that necessitates a molecular diagnostic assay and, with adjustment or testing of the primers, could be applied to any group for which development of rDNA profiles in a benchtop setting would prove useful.
A randomised study of nurse collected venous blood and self-collected dried blood spots for the assessment of cardiovascular risk factors in the Understanding Society Innovation Panel
Authors: Kumari Meena , Andrayas Alexandria , Al Baghal Tarek , Burton Jonathan , Crossley Thomas F. , Jones Kerry S. , Parkington Damon A. , Koulman Albert , Benzeval Michaela
Published: August 2023

Dried blood spot (DBS) sample collection has been suggested as a less invasive, cheaper and more convenient alternative to venepuncture, which requires trained personnel, making it a potentially viable approach for self-collection of blood on a large scale. We examine whether participants in a longitudinal survey were willing to provide a DBS sample in different interview settings, and how resulting cardiovascular risk biomarkers compared with those from venous blood to calculate clinical risk. Participants of the Understanding Society Innovation Panel, a representative sample of UK households, were randomly assigned to three modes of interview. Most participants (84%) were interviewed in their allocated mode. Participants (n = 2162) were interviewed by a nurse who collected both a blood sample by venepuncture and a DBS card (‘nurse collection’) or participants were seen by an interviewer or took part in the survey online to self-collect a DBS card (‘self-collection’). All DBS cards were returned in the post after the sample had dried. Lipids (total cholesterol, HDL-cholesterol, triglycerides), HbA1c and C-reactive protein were measured in venous and DBS samples and equivalence was calculated. The resultant values were used to confirm equivalent prevalence of risk of cardiovascular disease in each type of blood sample by mode of participation. Of participants interviewed by a nurse 69% consented to venous blood sample and 74% to a DBS sample, while in the self-collection modes, 35% consented to DBS collection. Demographic characteristics of participants in self-collection mode was not different to those in nurse collection mode. The percentage of participants with clinically raised biomarkers did not significantly differ between type of blood collection (for example, 62% had high cholesterol (> 5 mmol/l) measured by venepuncture and 67% had high cholesterol within the self-collected DBS sample (p = 0.13)). While self-collected DBS sampling had a lower response rate to DBS collected by a nurse, participation did not vary by key demographic characteristics. This study demonstrates that DBS collection is a feasible method of sample collection that can provide acceptable measures of clinically relevant biomarkers, enabling the calculation of population levels of cardiovascular disease risk.
Upwelling intensity and source water properties drive high interannual variability of corrosive events in the California Current
Authors: Cheresh Julia , Kroeker Kristy J. , Fiechter Jerome
Published: August 2023

Ocean acidification is progressing rapidly in the California Current System (CCS), a region already susceptible to reduced aragonite saturation state due to seasonal coastal upwelling. Results from a high-resolution (~ 3 km), coupled physical-biogeochemical model highlight that the intensity, duration, and severity of undersaturation events exhibit high interannual variability along the central CCS shelfbreak. Variability in dissolved inorganic carbon (DIC) along the bottom of the 100-m isobath explains 70–90% of event severity variance over the range of latitudes where most severe conditions occur. An empirical orthogonal function (EOF) analysis further reveals that interannual event variability is explained by a combination coastal upwelling intensity and DIC content in upwelled source waters. Simulated regional DIC exhibits low frequency temporal variability resembling that of the Pacific Decadal Oscillation, and is explained by changes to water mass composition in the CCS. While regional DIC concentrations and upwelling intensity individually explain 9 and 43% of year-to-year variability in undersaturation event severity, their combined influence accounts for 66% of the variance. The mechanistic description of exposure to undersaturated conditions presented here provides important context for monitoring the progression of ocean acidification in the CCS and identifies conditions leading to increased vulnerability for ecologically and commercially important species.
Sociodemographic and work-related differences in teachers’ attitude towards and perceived stress from emergency remote teaching during the COVID-19 pandemic
Authors: Kalo Kristin , Koestner Clemens , Dicks Theresa , Eggert Viktoria , Beutel Till , Zähme Carolina , Letzel Stephan , Dietz Pavel
Published: August 2023

The aim was to investigate the attitude towards and perceived stress from emergency remote teaching (ERT) among teachers during the COVID-19 pandemic. A Germany-wide online survey was conducted among teachers from all school types in March 2021. Data from 31,089 teachers entered analysis. ANOVAs or Welch’s t-tests with post-hoc analyses were performed to determine sociodemographic and work-related group differences in teachers’ attitude towards and perceived stress from ERT. The mean attitude towards ERT was 3.47 (± .84) out of 5 and the mean perceived stress was 5.03 (± .62) out of 6. Regarding the attitude towards ERT, we revealed significant differences for gender, age groups, number of children, occupational group, school management membership, and employment status (p < .05). Regarding perceived stress, significant differences were obtained for gender, age groups, and employment status (p < .05). A more positive attitude towards ERT seems to be associated with lower stress levels. Being female, a higher age, a higher number of children living in the own household as well as working full-time might hinder an effective implementation of remote teaching in school settings in Germany. Policy-makers and schools should think of strategies to improve the attitude towards and decrease perceived stress from remote teaching. This could include subgroup-specific training on the use of digital media, adapted to the work environment.
Crystallinity assessment of anthropogenic calcites using Raman micro-spectroscopy
Authors: Toffolo Michael B. , Pinkas Iddo , Gallo Ana Álvaro , Boaretto Elisabetta
Published: August 2023

Anthropogenic calcite is a form of calcium carbonate produced through pyrotechnological activities, and it is the main component of materials such as lime binders and wood ash. This type of calcite is characterized by a significantly lower degree of crystallinity compared with its geogenic counterparts, as a result of different formation processes. The crystallinity of calcite can be determined using infrared spectroscopy in transmission mode, which allows decoupling particle size effect from atomic order and thus effectively distinguish anthropogenic and geogenic calcites. On the contrary, Raman micro-spectroscopy is still in the process of developing a reference framework for the assessment of crystallinity in calcite. Band broadening has been identified as one of the proxies for crystallinity in the Raman spectra of geogenic and anthropogenic calcites. Here we analyze the full width at half maximum of calcite bands in various geogenic and anthropogenic materials, backed against an independent crystallinity reference based on infrared spectroscopy. Results are then used to assess the crystallinity of anthropogenic calcite in archaeological lime binders characterized by different states of preservation, including samples affected by the formation of secondary calcite, and tested on micromorphology thin sections in which lime binders are embedded in sediments.
Expression quantitative trait methylation analysis elucidates gene regulatory effects of DNA methylation: the Framingham Heart Study
Authors: Keshawarz Amena , Bui Helena , Joehanes Roby , Ma Jiantao , Liu Chunyu , Huan Tianxiao , Hwang Shih-Jen , Tejada Brandon , Sooda Meera , Courchesne Paul , Munson Peter J. , Demirkale Cumhur Y. , Yao Chen , Heard-Costa Nancy L. , Pitsillides Achilleas N. , Lin Honghuang , Liu Ching-Ti , Wang Yuxuan , Peloso Gina M. , Lundin Jessica , Haessler Jeffrey , Du Zhaohui , Cho Michael , Hersh Craig P. , Castaldi Peter , Raffield Laura M. , Wen Jia , Li Yun , Reiner Alexander P. , Feolo Mike , Sharopova Nataliya , Vasan Ramachandran S. , DeMeo Dawn L. , Carson April P. , Kooperberg Charles , Levy Daniel
Published: August 2023

Expression quantitative trait methylation (eQTM) analysis identifies DNA CpG sites at which methylation is associated with gene expression. The present study describes an eQTM resource of CpG-transcript pairs derived from whole blood DNA methylation and RNA sequencing gene expression data in 2115 Framingham Heart Study participants. We identified 70,047 significant cis CpG-transcript pairs at p < 1E−7 where the top most significant eGenes (i.e., gene transcripts associated with a CpG) were enriched in biological pathways related to cell signaling, and for 1208 clinical traits (enrichment false discovery rate [FDR] ≤ 0.05). We also identified 246,667 significant trans CpG-transcript pairs at p < 1E−14 where the top most significant eGenes were enriched in biological pathways related to activation of the immune response, and for 1191 clinical traits (enrichment FDR ≤ 0.05). Independent and external replication of the top 1000 significant cis and trans CpG-transcript pairs was completed in the Women’s Health Initiative and Jackson Heart Study cohorts. Using significant cis CpG-transcript pairs, we identified significant mediation of the association between CpG sites and cardiometabolic traits through gene expression and identified shared genetic regulation between CpGs and transcripts associated with cardiometabolic traits. In conclusion, we developed a robust and powerful resource of whole blood eQTM CpG-transcript pairs that can help inform future functional studies that seek to understand the molecular basis of disease.
Sarcomeric network analysis of ex vivo cultivated human atrial appendage tissue using super-resolution microscopy
Authors: Chabanovska Oleksandra , Lemcke Heiko , Lang Hermann , Vollmar Brigitte , Dohmen Pascal M. , David Robert , Etz Christian , Neßelmann Catharina
Published: August 2023

Investigating native human cardiac tissue with preserved 3D macro- and microarchitecture is fundamental for clinical and basic research. Unfortunately, the low accessibility of the human myocardium continues to limit scientific progress. To overcome this issue, utilizing atrial appendages of the human heart may become highly beneficial. Atrial appendages are often removed during open-heart surgery and can be preserved ex vivo as living tissue with varying durability depending on the culture method. In this study, we prepared living thin myocardial slices from left atrial appendages that were cultured using an air-liquid interface system for overall 10 days. Metabolic activity of the cultured slices was assessed using a conventional methyl thiazolyl tetrazolium (MTT) assay. To monitor the structural integrity of cardiomyocytes within the tissue, we implemented our recently described super-resolution microscopy approach that allows both qualitative and quantitative in-depth evaluation of sarcomere network based on parameters such as overall sarcomere content, filament size and orientation. Additionally, expression of mRNAs coding for key structural and functional proteins was analyzed by real-time reverse transcription polymerase chain reaction (qRT-PCR). Our findings demonstrate highly significant disassembly of contractile apparatus represented by degradation of $$\alpha $$
α
-actinin filaments detected after three days in culture, while metabolic activity was constantly rising and remained high for up to seven days. However, gene expression of crucial cardiac markers strongly decreased after the first day in culture indicating an early destructive response to ex vivo conditions. Therefore, we suggest static cultivation of living myocardial slices derived from left atrial appendage and prepared according to our protocol only for short-termed experiments (e.g. medicinal drug testing), while introduction of electro-mechanical stimulation protocols may offer the possibility for long-term integrity of such constructs.