bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing a health promoting university in Trinity College Dublin—overview and outline process evaluation
Authors: Darker Catherine D , Mullin Martina , Doyle Louise , Tanner Michelle , McGrath David , Doherty Lena , Dreyer-Gibney Katrin , Barrett Emer M , Flynn Deirdre , Murphy Patricia , Ivers Jo-Hanna H , Burke Eilish , Ryan Michele , McCarron Mary , Murphy Paula , Sheils Orla , Hevey David , Leen Aisling , Keogh Leah , Walls Breda , Bennett Annemarie E , Petersen Freja , Nolan Ann , Barry Joe M
Published: October 2021

Higher Education Institutions (HEIs) have the potential to impact positively on the health and wellbeing of their staff and students. Using and expanding on the ‘health promoting university’ (HPU) platform within HEIs, this article provides a description of ‘Healthy Trinity’, which is an initiative underway in Trinity College Dublin, the University of Dublin. First, Healthy Trinity is contextualized in background literature including international and national policy and practice. Second, an overview of Healthy Trinity is provided including its vision and goals. Third, the article describes the steps taken relating to the identification of stakeholders and use of a network and a co-lead model. Within this approach, the article describes a partnership approach whereby responsibilities regarding health and wellbeing are shared by individuals and the institution. Fourth, the design and implementation of Healthy Trinity is discussed by taking a ‘settings approach’, in which the emphasis for change is placed on individual behaviours, environment, policy and organizational culture. Consideration is given to the interplay between intervention, implementation strategy and context for successful systemic implementation. The fifth element presented is the early-stage challenges encountered during implementation, such as the need to secure recurrent funding and the importance of having a direct input to the governance of the University to enable systemic change. The sixth and final component of the article is an outline of Healthy Trinity’s intention to utilize a process evaluation of the early implementation phases of this complex intervention within a settings approach. Potential deliverables and impacts of this HPU initiative are presented and discussed.
Formation of keto-type ceramides in palmoplantar keratoderma based on biallelic KDSR mutations in patients
Authors: Pilz Robert , Opálka Lukáš , Majcher Adam , Grimm Elisabeth , Van Maldergem Lionel , Mihalceanu Silvia , Schäkel Knut , Enk Alexander , Aubin François , Bursztejn Anne-Claire , Brischoux-Boucher Elise , Fischer Judith , Sandhoff Roger
Published: October 2021

Functional skin barrier requires sphingolipid homeostasis; 3-ketodihydrosphingosine reductase or KDSR is a key enzyme of sphingolipid anabolism catalyzing the reduction of 3-ketodihydrosphingosine to sphinganine. Biallelic mutations in the KDSR gene may cause erythrokeratoderma variabilis et progressive-4, later specified as PERIOPTER syndrome, emphasizing a characteristic periorifical and ptychotropic erythrokeratoderma. We report another patient with compound heterozygous mutations in KDSR, born with generalized harlequin ichthyosis, which progressed into palmoplantar keratoderma. To determine whether patient-associated KDSR mutations lead to KDSR substrate accumulation and/or unrecognized sphingolipid downstream products in stratum corneum (SC), we analyzed lipids of this and previously published patients with non-identical biallelic mutations in KDSR. In SC of both patients, we identified ‘hitherto’ unobserved skin ceramides with an unusual keto-type sphingoid base in lesional and non-lesional areas, which accounted for up to 10% of the measured ceramide species. Furthermore, an overall shorter mean chain length of free and bound sphingoid bases was observed—shorter mean chain length of free sphingoid bases was also observed in lesional psoriasis vulgaris SC, but not generally in lesional atopic dermatitis SC. Formation of keto-type ceramides is probably due to a bottle neck in metabolic flux through KDSR and a bypass by ceramide synthases, which highlights the importance of tight intermediate regulation during sphingolipid anabolism and reveals substrate deprivation as potential therapy.
Crk and Crkl have shared functions in neural crest cells for cardiac outflow tract septation and vascular smooth muscle differentiation
Authors: Shi Lijie , Racedo Silvia E , Diacou Alexander , Park Taeju , Zhou Bin , Morrow Bernice E
Published: October 2021

CRK and CRKL encode cytoplasmic adaptors that contribute to the etiology of congenital heart disease. Neural crest cells (NCCs) are required for cardiac outflow tract (OFT) septation and aortic arch formation. The roles of Crk/Crkl in NCCs during mouse cardiovascular development remain unknown. To test this, we inactivated Crk and/or Crkl in NCCs. We found that the loss of Crk, rather than Crkl, in NCCs resulted in double outlet right ventricle, while loss of both Crk/Crkl in NCCs resulted in severe defects with earlier lethality due to failed OFT septation and severe dilation of the pharyngeal arch arteries (PAAs). We found that these defects are due to altered cell morphology resulting in reduced localization of NCCs to the OFT and failed integrity of the PAAs, along with reduced expression of Integrin signaling genes. Further, molecular studies identified reduced differentiation of vascular smooth muscle cells that may in part be due to altered Notch signaling. Additionally, there is increased cellular stress that leads to modest increase in apoptosis. Overall, this explains the mechanism for the Crk/Crkl phenotype.
Hybrid stochastic differential systems in pharmacokinetics
Authors: Baili Hana
Published: October 2021

Modelling patient medication poor compliance combined with the inherent uncertainty in a bioavailability trial leads recognizably to the fact that plasma concentration-time curve must be treated as a random process. We suggest for modelling a general class of hybrid stochastic differential systems (HSDS). Roughly speaking, a HSDS is a piecewise diffusion process with jumps of two types: spontaneous and predictable. The essential tasks for us afterwards are to identify the model ingredients and to derive its bearings; of interest are a couple of operators associated to every Markov process: the generating operator and the Fokker–Planck operator. The model induces a Fokker–Planck–Kolmogorov equation along with moment equations, and computations based on direct solutions of the latter make it possible to study the variability of the concentration around its mean as compared to the full compliance case and to assess the effect of some parameters such as the intake and elimination rates.
Phenotypic and genomic analysis reveals Riemerella anatipestifer as the potential reservoir of tet(X) variants
Authors: Li Ruichao , Jiang Yongjia , Peng Kai , Wang Yanhong , Wang Mianzhi , Liu Yuan , Wang Zhiqiang
Published: October 2021

Background

Tigecycline is regarded as one of the last-resort antimicrobials clinically. Emergence of plasmid-mediated tet(X) undermines such an important drug. However, the origins of tet(X) remain largely unexplored.

Methods

Riemerella anatipestifer strains were characterized by PCR, antimicrobial susceptibility testing, WGS and bioinformatics analysis. Functional analysis of tet(X) was verified by cloning experiments. Genomic structures of chromosome- and plasmid-mediated tet(X) were analysed.

Results

Thirty-eight R. anatipestifer strains were collected and found to be positive for tet(X). These strains were resistant to multiple antimicrobials; 55.3% (21/38) of the strains were resistant to tigecycline and all of the strains demonstrated resistance to tetracycline. The complete genome sequences of 18 representative strains were obtained. WGS analysis of 38 genomes identified 13 tet(X) variants located on chromosomes, which increased MICs of tigecycline (16–256-fold) for Escherichia coli, although most of them could not confer high-level resistance to tigecycline in the original R. anatipestifer hosts. Genomic environment analysis indicated that the occurrence of multiple tet(X) variants is common and other resistance genes, such as catB, tet(Q), floR, blaOXA, ereD and ermF, could be located in the same chromosomal regions. Two types of tet(X)-bearing segments were identified, one of which was floR-ISCR2-tet(X). This indicates that tet(X) variants were not conserved in chromosomal structures, but in regions with potential transferability. Furthermore, an MDR plasmid carrying tet(X18) was found in R. anatipestifer 20190305E2-2, different from the chromosomal tet(X21).

Conclusions

This study confirmed that tet(X) is highly prevalent in R. anatipestifer. The transfer risk of tet(X) across R. anatipestifer to other clinical pathogens warrants further investigations.
Establishing a research informatics program in a public healthcare system: a case report with model documents
Authors: Meeker Daniella , Fu Paul , Garcia Gary , Dyer Irene E , Yadav Kabir , Fleishman Ross , Yee Hal F
Published: October 2021

While much is known about governance models for research informatics programs in academic medical centers and similarly situated cancer centers, community and public health systems have been less well-characterized. As part of implementing an enterprise research governance framework, leaders in the Los Angeles County Department of Health Services established a research informatics program, including research data warehousing. The strategy is focused on high-priority, patient-centered research that leverages the investment in health IT and an efficient, sustained contribution from 2 affiliated Clinical Translational Sciences Institutes. This case study describes the foundational governance framework and policies that were developed. We share the results of several years of planning, implementation, and operations of an academically funded research informatics service core embedded in a large, multicenter county health system. We include herein a Supplementary Appendix of governance documents that may serve as pragmatic models for similar initiatives.
FeedingSaccharomyces cerevisiaefermentation products lessens the severity of a viral–bacterial coinfection in preweaned calves
Authors: McDonald Paiton O , Schill Courtney , Maina Teresia W , Samuel Beulah , Porter Madison , Yoon Ilkyu , McGill Jodi L
Published: October 2021

We have previously reported that supplementation with Saccharomyces cerevisiae fermentation products (SCFP) ameliorates clinical signs and lung pathology following experimental bovine respiratory syncytial virus (BRSV) infection in preweaned dairy calves. The objectives of this study were to determine the effect of SCFP supplementation on the metabolic and endocrine responses, and disease outcome of a viral–bacterial coinfection in preweaned calves. Twenty-seven, 1- to 2-d-old Holstein-Angus cross calves were enrolled in the study; one SCFP calf was removed from the trial during the pre-challenge phase due to complications from nephritis. Calves were assigned to two treatment groups: control or SCFP-treated, base milk replacer with 1 g/d SCFP (Smartcare, soluble formula) and calf starter top dressed with 5 g/d SCFP (NutriTek, insoluble formula). Calves were infected with BRSV on day 21, followed 6 d later by intratracheal inoculation with Pasteurella multocida (PM). Calves were euthanized on day 10 post-viral infection. Calves receiving SCFP had reduced thoracic ultrasonography scores on day 7 post-viral infection (P = 0.03) and a tendency toward reduced scores on day 10 post-viral infection (P = 0.09). Calves receiving SCFP also had less severe lung pathology scores at necropsy (P = 0.06). No differences between treatments were observed in lung viral loads (P = 0.48) or bacterial lung recovery (P = 0.34); however, there was a distinction in the lung location for PM recovery, with PM isolated more frequently from the cranial lobes in SCFP-treated calves, but more frequently from the caudal lobes of control calves. Calves treated with SCFP tended (P = 0.07) to have higher serum IL-6 concentrations following the coinfection. Calves treated with SCFP had lower concentrations of serum nonesterified fatty acids and beta-hydroxybutyric acid compared with controls following experimental challenge (P = 0.03 and P = 0.08, respectively), suggesting metabolic changes favoring growth and development. There were no differences between groups in gene expression of insulin receptor, insulin-like growth factor 1 (IGF-1), IGF-1 receptor (IGF-1R), growth hormone receptor, or haptoglobin in the liver. Results from this study suggest that supplementing with SCFP may moderate the impact of a respiratory viral–bacterial coinfection on preweaned calves through metabolic and immune modifications.
Mitochondria as environments for the nuclear genome in Drosophila: mitonuclear G×G×E
Authors: Rand David M , Mossman James A , Spierer Adam N , Santiago John A
Published: October 2021

Mitochondria evolved from a union of microbial cells belonging to distinct lineages that were likely anaerobic. The evolution of eukaryotes required a massive reorganization of the 2 genomes and eventual adaptation to aerobic environments. The nutrients and oxygen that sustain eukaryotic metabolism today are processed in mitochondria through coordinated expression of 37 mitochondrial genes and over 1000 nuclear genes. This puts mitochondria at the nexus of gene-by-gene (G×G) and gene-by-environment (G×E) interactions that sustain life. Here we use a Drosophila model of mitonuclear genetic interactions to explore the notion that mitochondria are environments for the nuclear genome, and vice versa. We construct factorial combinations of mtDNA and nuclear chromosomes to test for epistatic interactions (G×G), and expose these mitonuclear genotypes to altered dietary environments to examine G×E interactions. We use development time and genome-wide RNAseq analyses to assess the relative contributions of mtDNA, nuclear chromosomes, and environmental effects on these traits (mitonuclear G×G×E). We show that the nuclear transcriptional response to alternative mitochondrial “environments” (G×G) has significant overlap with the transcriptional response of mitonuclear genotypes to altered dietary environments. These analyses point to specific transcription factors (e.g., giant) that mediated these interactions, and identified coexpressed modules of genes that may account for the overlap in differentially expressed genes. Roughly 20% of the transcriptome includes G×G genes that are concordant with G×E genes, suggesting that mitonuclear interactions are part of an organism’s environment.
Cancer among children, adolescents and young adults in the Hokushin region, Japan, between 2010 and 2015
Authors: Okura Eri , Nishino Yoshikazu , Sakashita Kazuo , Tanimoto Azusa , Hayashi Ryuji , Yoshida Yoshio , Nakada Mitsutoshi , Koizumi Tomonobu , Yano Seiji , Nakazawa Yozo
Published: October 2021

Adolescents and young adults with cancer encounter age-related challenges. Cancer treatment and support are not always tailored to the needs of each patient due to difficulty in the collection of accurate data. The present study aimed to investigate cancer among children and adolescents and young adults in the four adjacent prefectures of Japan (Toyama, Ishikawa, Fukui and Nagano) by analyzing data from a unique regional cancer database. We retrieved and analyzed the data of pediatric and adolescent and young adult patients aged between 0 and 39 years at cancer diagnosis (including carcinoma in situ), which was registered in the Hokushin Ganpro database between 2010 and 2015. A total of 5718 cases (1571 males and 4147 females) were identified during this period. The overall male-to-female ratio was 1:2.6. There was no distinct difference in the number of cancer cases per 100 000 population between males and females until 19 years of age. The difference became more pronounced after 20 years of age. The number of cancer cases (per 100 000 population) in the 0–14-, 15–19-, 20–29- and 30–39-year age groups was estimated to be 13.4, 14.5, 44.0 and 101.5, respectively. Carcinomas were the most common type of cancer in the adolescents and young adults (15–39 years) population (74%), whereas they were not the predominant cancer type in the pediatric (0–14 years) population. Although further research is needed to understand the needs of adolescents and young adults with cancer, we believe that our findings will help guide efforts to improve the management strategy for adolescents and young adults with cancer.
State Responsibility for the Conduct of Rebels in Situations of Unsuccessful Civil Wars: A Critical Analysis of the Cengiz v Libya Case
Authors: Dumberry Patrick
Published: October 2021

Based on an analysis of State practice and case law, this article examines one basic principle embodied in Article 10 of the International Law Commission Articles (ILC) on State responsibility: the wrongful acts committed by rebels during an insurrection or a civil war are not attributable to the State once the government defeats the insurgency. The article examines how investment tribunals can use Article 10 in the context of investor–State arbitration proceedings involving rebellions and civil wars. I will critically analyse the recent Cengiz v. Libya award rendered in the context of Libya’s civil war. I will show that the Tribunal failed to correctly applied Articles 4 and 10 of the ILC Articles. I will explain how the Tribunal could have made better use of the principles embodied in Article 10 to solve matters of State responsibility and attribution it was facing.
Action mechanisms of small microbial volatile compounds in plants
Authors: Gámez-Arcas Samuel , Baroja-Fernández Edurne , García-Gómez Pablo , Muñoz Francisco José , Almagro Goizeder , Bahaji Abdellatif , Sánchez-López Ángela María , Pozueta-Romero Javier
Published: October 2021

Microorganisms communicate with plants by exchanging chemical signals throughout the phytosphere. Before direct contact with plants occurs, beneficial microorganisms emit a plethora of volatile compounds that promote plant growth and photosynthesis as well as developmental, metabolic, transcriptional, and proteomic changes in plants. These compounds can also induce systemic drought tolerance and improve water and nutrient acquisition. Recent studies have shown that this capacity is not restricted to beneficial microbes; it also extends to phytopathogens. Plant responses to microbial volatile compounds have frequently been associated with volatile organic compounds with molecular masses ranging between ~ 45Da and 300Da. However, microorganisms also release a limited number of volatile compounds with molecular masses of less than ~45Da that react with proteins and/or act as signaling molecules. Some of these compounds promote photosynthesis and growth when exogenously applied in low concentrations. Recently, evidence has shown that small volatile compounds are important determinants of plant responses to microbial volatile emissions. However, the regulatory mechanisms involved in these responses remain poorly understood. This review summarizes current knowledge of biochemical and molecular mechanisms involved in plant growth, development, and metabolic responses to small microbial volatile compounds.
Belowground plant–microbe communications via volatile compounds
Authors: Sharifi Rouhallah , Jeon Je-Seung , Ryu Choong-Min
Published: October 2021

Volatile compounds play important roles in rhizosphere biological communications and interactions. The emission of plant and microbial volatiles is a dynamic phenomenon that is affected by several endogenous and exogenous signals. Diffusion of volatiles can be limited by their adsorption, degradation, and dissolution under specific environmental conditions. Therefore, rhizosphere volatiles need to be investigated on a micro and spatiotemporal scale. Plant and microbial volatiles can expand and specialize the rhizobacterial niche not only by improving the root system architecture such that it serves as a nutrient-rich shelter, but also by inhibiting or promoting the growth, chemotaxis, survival, and robustness of neighboring organisms. Root volatiles play an important role in engineering the belowground microbiome by shaping the microbial community structure and recruiting beneficial microbes. Microbial volatiles are appropriate candidates for improving plant growth and health during environmental challenges and climate change. However, some technical and experimental challenges limit the non-destructive monitoring of volatile emissions in the rhizosphere in real-time. In this review, we attempt to clarify the volatile-mediated intra- and inter-kingdom communications in the rhizosphere, and propose improvements in experimental design for future research.
Dual functionality of natural mixtures of bacterial volatile compounds on plant growth
Authors: Song Geun Cheol , Jeon Je-Seung , Sim Hee-Jung , Lee Soohyun , Jung Jihye , Kim Sang-Gyu , Moon Sun Young , Ryu Choong-Min
Published: October 2021

Bacteria emit volatile compounds that modulate plant growth. Previous studies reported the impacts of bacterial volatile compounds on plant growth; however, the results varied depending on bacterial nutrient availability. We investigated whether the effects of plant growth–inhibiting volatiles (PGIVs) and plant growth–promoting volatiles (PGPVs) depended on the perceived dose by evaluating the growth of Arabidopsis thaliana seedlings placed at 7, 14, and 21 cm away from Bacillus amyloliquefaciens GB03 colonies growing in rich medium. A large bacterial colony (500 μl inoculum) inhibited plant growth at 7 cm and promoted growth at 21 cm, whereas a small bacterial colony (100 μl inoculum) induced the opposite pattern of response. We identified pyrazine and 2,5-dimethylpyrazine as candidate PGIVs that significantly reduced plant growth at a distance of 7 cm. PGIV effects were validated by exposing plants to synthetic 2,5-dimethylpyrazine and bacteria emitting PGPVs, which showed that PGIVs overwhelm PGPVs to rapidly increase salicylic acid content and related gene expression. This is referred to as the defence-growth trade-off. Our results indicate that high PGIV concentrations suppress plant growth and promote immunity, whereas low PGPV concentrations promote growth. This study provides novel insights into the complex effects of bacterial volatile mixtures and fine-tuning of bacteria-plant interactions.
Pneumocystis jirovecii genetic diversity in a Spanish tertiary hospital
Authors: Goterris Lidia , Pasic Lana , Guerrero Murillo Mercedes , Kan Alex , Anton Andres , Aguilar Company Juan , Ruiz-Camps Isabel , Meyer Wieland , Martin-Gomez María Teresa
Published: October 2021

Pneumocystis jirovecii is associated with non-noxious colonization or severe pneumonia in immunocompromised hosts. Epidemiological investigations have been hampered by the lack of a standardized typing scheme. Thus, only partial molecular data on Spanish P. jirovecii cases are available. Recently, a new ISHAM consensus multilocus sequence typing scheme (MLST) targeting β-TUB, mt26S, CYB, and SOD with a publicly accessible database has been launched to overcome this problem.

 The molecular epidemiology of P. jirovecii from immunocompromised patients either colonized (n = 50) or having pneumonia (n = 36) seen between 2014 and 2018 at a single center in Barcelona, Spain, was studied. The new ISHAM consensus MSLT scheme was used to investigate the local epidemiology and identify possible unnoticed outbreaks. Mutations in the DHPS gene, not included in the scheme but giving information about potential sulfa treatment failure, were also studied. The study assigned 32 sequence types (ST) to 72.2% pneumonia and 56% colonization cases. The most frequent STs were ST21 (18.5%), ST22 (14.8%), and ST37(14.8%). For non-unique STs, ST3, ST30 and ST31 were found only in pneumonia cases, whereas ST27 was associated exclusively to colonizations. Despite 38 patients sharing similar STs, only two were involved in a potential cross transmission event. No DHPS mutations were identified. The new consensus typing scheme was useful to ascertain the molecular epidemiology of P. jirovecii in our center revealing a high genetic diversity and the potential association of specific STs to colonization and pneumonia cases.

Lay Summary

A newly described MLST scheme aims at providing a standardized tool to study and compare Pneumocystis jirovecii epidemiology. A high diversity among P. jirovecii isolates from patients in Barcelona, Spain, and a potential association between specific STs and infection/colonization were identified.
Indicator power spectra: surgical excision of non-linearities and covariance matrices for counts in cells
Authors: Repp Andrew , Szapudi István
Published: October 2021

We here introduce indicator functions, which identify regions of a given density in order to characterize the density dependence of clustering. After a general introduction to this tool, we show that indicator-function power spectra are biased versions of the linear spectrum on large scales. We provide a calculation from first principles for this bias, we show that it reproduces simulation results, and we provide a simple functional form for the translinear portion of the indicator-function spectra. We also outline two applications: First, these spectra facilitate surgical excision of non-linearity, and thus, significantly increase the reach of linear theory. Second, indicator-function spectra permit calculation of theoretical covariance matrices for counts-in-cells (CIC), facilitating parameter estimation with complementary CIC methods.
Convolutional deep denoising autoencoders for radio astronomical images
Authors: Gheller C , Vazza F
Published: October 2021

We apply a Machine Learning technique known as Convolutional Denoising Autoencoder to denoise synthetic images of state-of-the-art radio telescopes, with the goal of detecting the faint, diffused radio sources predicted to characterize the radio cosmic web. In our application, denoising is intended to address both the reduction of random instrumental noise and the minimization of additional spurious artefacts like the sidelobes, resulting from the aperture synthesis technique. The effectiveness and the accuracy of the method are analysed for different kinds of corrupted input images, together with its computational performance. Specific attention has been devoted to create realistic mock observations for the training, exploiting the outcomes of cosmological numerical simulations, to generate images corresponding to LOFAR HBA 8 h observations at 150 MHz. Our autoencoder can effectively denoise complex images identifying and extracting faint objects at the limits of the instrumental sensitivity. The method can efficiently scale on large data sets, exploiting high-performance computing solutions, in a fully automated way (i.e. no human supervision is required after training). It can accurately perform image segmentation, identifying low brightness outskirts of diffused sources, proving to be a viable solution for detecting challenging extended objects hidden in noisy radio observations.
Probabilistic orbits and dynamical masses of emission-line binaries
Authors: Grant David , Blundell Katherine
Published: October 2021

The observed orbits of emission-line stars may be affected by systematics owing to their broad emission lines being formed in complex and extended environments. This is problematic when orbital parameter probability distributions are estimated assuming radial-velocity data are solely comprised of Keplerian motion plus Gaussian white noise, leading to overconfident and inaccurate orbital solutions, with implications for the inferred dynamical masses and hence evolutionary models. We present a framework in which these systems can be meaningfully analysed. We synthesize benchmark data sets, each with a different and challenging noise formulation, for testing the performance of different algorithms. We make these data sets freely available with the aim of making model validation an easy and standardized practice in this field. Next, we develop an application of Gaussian processes to model the radial-velocity systematics of emission-line binaries, named marginalized $\mathcal {GP}$. We benchmark this algorithm, along with current standardized algorithms, on the synthetic data sets and find our marginalized $\mathcal {GP}$ algorithm performs significantly better than the standard algorithms for data contaminated by systematics. Finally, we apply the marginalized $\mathcal {GP}$ algorithm to four prototypical emission-line binaries: Eta Carinae, GG Carinae, WR 140, and WR 133. We find systematics to be present in several of these case studies; and consequently, the predicted orbital parameter distributions, and dynamical masses, are modified from those previously determined.
The spatial distribution deviation and the power suppression of baryons from dark matter
Authors: Yang Hua-Yu , Wang Yun , He Ping , Zhu Weishan , Feng Long-Long
Published: October 2021

The spatial distribution between dark matter and baryonic matter of the Universe is biased or deviates from each other. In this work, by comparing the results derived from IllustrisTNG and WIGEON simulations, we find that many results obtained from TNG are similar to those from WIGEON data, but differences between the two simulations do exist. For the ratio of density power spectrum between dark matter and baryonic matter, as scales become smaller and smaller, the power spectra for baryons are increasingly suppressed for WIGEON simulations; while for TNG simulations, the suppression stops at $k=15-20\, {h {\rm Mpc}^{-1}}$, and the power spectrum ratios increase when $k\gt 20\, {h {\rm Mpc}^{-1}}$. The suppression of power ratio for WIGEON is also redshift-dependent. From z = 1 to z = 0, the power ratio decreases from about 70 per cent to less than 50 per cent at $k=8\, {h {\rm Mpc}^{-1}}$. For TNG simulation, the suppression of power ratio is enhanced with decreasing redshifts in the scale range $k\gt 4\, {h {\rm Mpc}^{-1}}$, but is nearly unchanged with redshifts in $k\lt 4\, {h {\rm Mpc}^{-1}}$. These results indicate that turbulent heating can also have the consequence to suppress the power ratio between baryons and dark matter. Regarding the power suppression for TNG simulations as the norm, the power suppression by turbulence for WIGEON simulations is roughly estimated to be 45 per cent at $k=2\, {h {\rm Mpc}^{-1}}$, and gradually increases to 69 per cent at $k=8\, {h {\rm Mpc}^{-1}}$, indicating the impact of turbulence on the cosmic baryons are more significant on small scales.
SKAO H i intensity mapping: blind foreground subtraction challenge
Authors: Spinelli Marta , Carucci Isabella P , Cunnington Steven , Harper Stuart E , Irfan Melis O , Fonseca José , Pourtsidou Alkistis , Wolz Laura
Published: October 2021

Neutral Hydrogen Intensity Mapping (H i IM) surveys will be a powerful new probe of cosmology. However, strong astrophysical foregrounds contaminate the signal and their coupling with instrumental systematics further increases the data cleaning complexity. In this work, we simulate a realistic single-dish H i IM survey of a 5000 deg2 patch in the 950–1400 MHz range, with both the MID telescope of the SKA Observatory (SKAO) and MeerKAT, its precursor. We include a state-of-the-art H i simulation and explore different foreground models and instrumental effects such as non-homogeneous thermal noise and beam side lobes. We perform the first Blind Foreground Subtraction Challenge for H i IM on these synthetic data cubes, aiming to characterize the performance of available foreground cleaning methods with no prior knowledge of the sky components and noise level. Nine foreground cleaning pipelines joined the challenge, based on statistical source separation algorithms, blind polynomial fitting, and an astrophysical-informed parametric fit to foregrounds. We devise metrics to compare the pipeline performances quantitatively. In general, they can recover the input maps’ two-point statistics within 20 per cent in the range of scales least affected by the telescope beam. However, spurious artefacts appear in the cleaned maps due to interactions between the foreground structure and the beam side lobes. We conclude that it is fundamental to develop accurate beam deconvolution algorithms and test data post-processing steps carefully before cleaning. This study was performed as part of SKAO preparatory work by the H i IM Focus Group of the SKA Cosmology Science Working Group.
Redshift-space effects in voids and their impact on cosmological tests – II. The void-galaxy cross-correlation function
Authors: Correa Carlos M , Paz Dante J , Padilla Nelson D , Sánchez Ariel G , Ruiz Andrés N , Angulo Raúl E
Published: October 2021

This is the second part of a thorough investigation of the redshift-space effects that affect void properties and the impact they have on cosmological tests. Here, we focus on the void-galaxy cross-correlation function, specifically, on the projected versions that we developed in a previous work. The pillar of the analysis is the one-to-one relationship between real and redshift-space voids above the shot-noise level identified with a spherical void finder. Under this mapping, void properties are affected by three effects: (i) a systematic expansion as a consequence of the distortions induced by galaxy dynamics, (ii) the Alcock–Paczynski volume effect, which manifests as an overall expansion or contraction depending on the fiducial cosmology, and (iii) a systematic off-centring along the line of sight as a consequence of the distortions induced by void dynamics. We found that correlations are also affected by an additional source of distortions: the ellipticity of voids. This is the first time that distortions due to the off-centring and ellipticity effects are detected and quantified. With a simplified test, we verified that the Gaussian streaming model is still robust provided all these effects are taken into account, laying the foundations for improvements in current models in order to obtain unbiased cosmological constraints from spectroscopic surveys. Besides this practical importance, this analysis also encodes key information about the structure and dynamics of the Universe at the largest scales. Furthermore, some of the effects constitute cosmological probes by themselves, as is the case of the void ellipticity.
Simulating the complexity of the dark matter sheet – II. Halo and subhalo mass functions for non-cold dark matter models
Authors: Stücker Jens , Angulo Raul E , Hahn Oliver , White Simon D M
Published: October 2021

We present ‘sheet + release’ simulations that reliably follow the evolution of dark matter structure at and below the dark matter free-streaming scale, where instabilities in traditional N-body simulations create a large population of spurious artificial haloes. Our simulations sample a large range of power-spectrum cutoff functions, parameterized through the half-mode scale khm and a slope parameter β. This parameter space can represent many non-cold dark matter (NCDM) models, including thermal relic warm dark matter, sterile-neutrinos, fuzzy dark matter, and a significant fraction of ETHOS models. Combining these simulations with additional N-body simulations, we find the following results. (1) Even after eliminating spurious haloes, the halo mass function in the strongly suppressed regime ($n_{\rm {X}}/n_{\rm {CDM}} \lt 5 \ \mathrm{ per \, cent}$) remains uncertain because it depends strongly on the definition of a halo. At these mass scales traditional halo finders primarily identify overdensities that are unbound, highly elongated, dominated by tidal fields, or far from virialized. (2) The regime where the suppression is smaller than a factor of 20 is quite robust to these uncertainties, however, and can be inferred reliably from suitable N-body simulations. (3) Parameterizing the suppression in the halo- and subhalo mass functions through the scales where the suppression reaches $20 \ \mathrm{ per \, cent}$, 50 per cent, and $80 \ \mathrm{ per \, cent}$, we provide simple formulae which enable predictions for many NCDM models. (4) The halo mass–concentration relations in our sheet + release simulations agree well with previous results based on N-body simulations. (5) In general, we confirm the validity of previous N-body studies of warm dark matter models, largely eliminating concerns about the effects of artificial haloes.
The 2D metallicity distribution and mixing scales of nearby galaxies
Authors: Williams Thomas G , Kreckel Kathryn , Belfiore Francesco , Groves Brent , Sandstrom Karin , Santoro Francesco , Blanc Guillermo A , Bigiel Frank , Boquien Médéric , Chevance Mélanie , Congiu Enrico , Emsellem Eric , Glover Simon C O , Grasha Kathryn , Klessen Ralf S , Koch Eric , Kruijssen J M Diederik , Leroy Adam K , Liu Daizhong , Meidt Sharon , Pan Hsi-An , Querejeta Miguel , Rosolowsky Erik , Saito Toshiki , Sánchez-Blázquez Patricia , Schinnerer Eva , Schruba Andreas , Watkins Elizabeth J
Published: October 2021

Understanding the spatial distribution of metals within galaxies allows us to study the processes of chemical enrichment and mixing in the interstellar medium. In this work, we map the 2D distribution of metals using a Gaussian Process Regression (GPR) for 19 star-forming galaxies observed with the Very Large Telescope/Multi Unit Spectroscopic Explorer (VLT–MUSE) as a part of the PHANGS–MUSE survey. We find that 12 of our 19 galaxies show significant 2D metallicity variation. Those without significant variations typically have fewer metallicity measurements, indicating this is due to the dearth of ${\rm H\, {\small II}}$ regions in these galaxies, rather than a lack of higher-order variation. After subtracting a linear radial gradient, we see no enrichment in the spiral arms versus the disc. We measure the 50 per cent correlation scale from the two-point correlation function of these radially subtracted maps, finding it to typically be an order of magnitude smaller than the fitted GPR kernel scale length. We study the dependence of the two-point correlation scale length with a number of global galaxy properties. We find no relationship between the 50 per cent correlation scale and the overall gas turbulence, in tension with existing theoretical models. We also find more actively star-forming galaxies, and earlier type galaxies have a larger 50 per cent correlation scale. The size and stellar mass surface density do not appear to correlate with the 50 per cent correlation scale, indicating that perhaps the evolutionary state of the galaxy and its current star formation activity is the strongest indicator of the homogeneity of the metal distribution.
RNase H is an exo- and endoribonuclease with asymmetric directionality, depending on the binding mode to the structural variants of RNA:DNA hybrids
Authors: Lee Hyunjee , Cho HyeokJin , Kim Jooyoung , Lee Sua , Yoo Jungmin , Park Daeho , Lee Gwangrog
Published: October 2021

RNase H is involved in fundamental cellular processes and is responsible for removing the short stretch of RNA from Okazaki fragments and the long stretch of RNA from R-loops. Defects in RNase H lead to embryo lethality in mice and Aicardi-Goutieres syndrome in humans, suggesting the importance of RNase H. To date, RNase H is known to be a non-sequence-specific endonuclease, but it is not known whether it performs other functions on the structural variants of RNA:DNA hybrids. Here, we used Escherichia coli RNase H as a model, and examined its catalytic mechanism and its substrate recognition modes, using single-molecule FRET. We discovered that RNase H acts as a processive exoribonuclease on the 3′ DNA overhang side but as a distributive non-sequence-specific endonuclease on the 5′ DNA overhang side of RNA:DNA hybrids or on blunt-ended hybrids. The high affinity of previously unidentified double-stranded (ds) and single-stranded (ss) DNA junctions flanking RNA:DNA hybrids may help RNase H find the hybrid substrates in long genomic DNA. Our study provides new insights into the multifunctionality of RNase H, elucidating unprecedented roles of junctions and ssDNA overhang on RNA:DNA hybrids.
Genome-wide mapping of G-quadruplex structures with CUT&Tag
Authors: Lyu Jing , Shao Rui , Kwong Yung Philip Yuk , Elsässer Simon J
Published: October 2021

Single-stranded genomic DNA can fold into G-quadruplex (G4) structures or form DNA:RNA hybrids (R loops). Recent evidence suggests that such non-canonical DNA structures affect gene expression, DNA methylation, replication fork progression and genome stability. When and how G4 structures form and are resolved remains unclear. Here we report the use of Cleavage Under Targets and Tagmentation (CUT&Tag) for mapping native G4 in mammalian cell lines at high resolution and low background. Mild native conditions used for the procedure retain more G4 structures and provide a higher signal-to-noise ratio than ChIP-based methods. We determine the G4 landscape of mouse embryonic stem cells (ESC), observing widespread G4 formation at active promoters, active and poised enhancers. We discover that the presence of G4 motifs and G4 structures distinguishes active and primed enhancers in mouse ESCs. Upon differentiation to neural progenitor cells (NPC), enhancer G4s are lost. Further, performing R-loop CUT&Tag, we demonstrate the genome-wide co-occurrence of single-stranded DNA, G4s and R loops at promoters and enhancers. We confirm that G4 structures exist independent of ongoing transcription, suggesting an intricate relationship between transcription and non-canonical DNA structures.
DisProt in 2022: improved quality and accessibility of protein intrinsic disorder annotation
Authors: Quaglia Federica , Mészáros Bálint , Salladini Edoardo , Hatos András , Pancsa Rita , Chemes Lucía B , Pajkos Mátyás , Lazar Tamas , Peña-Díaz Samuel , Santos Jaime , Ács Veronika , Farahi Nazanin , Fichó Erzsébet , Aspromonte Maria Cristina , Bassot Claudio , Chasapi Anastasia , Davey Norman E , Davidović Radoslav , Dobson Laszlo , Elofsson Arne , Erdős Gábor , Gaudet Pascale , Giglio Michelle , Glavina Juliana , Iserte Javier , Iglesias Valentín , Kálmán Zsófia , Lambrughi Matteo , Leonardi Emanuela , Longhi Sonia , Macedo-Ribeiro Sandra , Maiani Emiliano , Marchetti Julia , Marino-Buslje Cristina , Mészáros Attila , Monzon Alexander Miguel , Minervini Giovanni , Nadendla Suvarna , Nilsson Juliet F , Novotný Marian , Ouzounis Christos A , Palopoli Nicolás , Papaleo Elena , Pereira Pedro José Barbosa , Pozzati Gabriele , Promponas Vasilis J , Pujols Jordi , Rocha Alma Carolina Sanchez , Salas Martin , Sawicki Luciana Rodriguez , Schad Eva , Shenoy Aditi , Szaniszló Tamás , Tsirigos Konstantinos D , Veljkovic Nevena , Parisi Gustavo , Ventura Salvador , Dosztányi Zsuzsanna , Tompa Peter , Tosatto Silvio C E , Piovesan Damiano
Published: October 2021

The Database of Intrinsically Disordered Proteins (DisProt, URL: https://disprot.org) is the major repository of manually curated annotations of intrinsically disordered proteins and regions from the literature. We report here recent updates of DisProt version 9, including a restyled web interface, refactored Intrinsically Disordered Proteins Ontology (IDPO), improvements in the curation process and significant content growth of around 30%. Higher quality and consistency of annotations is provided by a newly implemented reviewing process and training of curators. The increased curation capacity is fostered by the integration of DisProt with APICURON, a dedicated resource for the proper attribution and recognition of biocuration efforts. Better interoperability is provided through the adoption of the Minimum Information About Disorder (MIADE) standard, an active collaboration with the Gene Ontology (GO) and Evidence and Conclusion Ontology (ECO) consortia and the support of the ELIXIR infrastructure.
The pioneer round of translation ensures proper targeting of ER and mitochondrial proteins
Authors: Park Joori , Chang Jeeyoon , Hwang Hyun Jung , Jeong Kwon , Lee Hyuk-Joon , Ha Hongseok , Park Yeonkyoung , Lim Chunghun , Woo Jae-Sung , Kim Yoon Ki
Published: October 2021

The pioneer (or first) round of translation of newly synthesized mRNAs is largely mediated by a nuclear cap-binding complex (CBC). In a transcriptome-wide analysis of polysome-associated and CBC-bound transcripts, we identify RN7SL1, a noncoding RNA component of a signal recognition particle (SRP), as an interaction partner of the CBC. The direct CBC–SRP interaction safeguards against abnormal expression of polypeptides from a ribosome–nascent chain complex (RNC)–SRP complex until the latter is properly delivered to the endoplasmic reticulum. Failure of this surveillance causes abnormal expression of misfolded proteins at inappropriate intracellular locations, leading to a cytosolic stress response. This surveillance pathway also blocks protein synthesis through RNC–SRP misassembled on an mRNA encoding a mitochondrial protein. Thus, our results reveal a surveillance pathway in which pioneer translation ensures proper targeting of endoplasmic reticulum and mitochondrial proteins.
R-loopBase: a knowledgebase for genome-wide R-loop formation and regulation
Authors: Lin Ruoyao , Zhong Xiaoming , Zhou Yongli , Geng Huichao , Hu Qingxi , Huang Zhihao , Hu Jun , Fu Xiang-Dong , Chen Liang , Chen Jia-Yu
Published: October 2021

R-loops play versatile roles in many physiological and pathological processes, and are of great interest to scientists in multiple fields. However, controversy about their genomic localization and incomplete understanding of their regulatory network raise great challenges for R-loop research. Here, we present R-loopBase (https://rloopbase.nju.edu.cn) to tackle these pressing issues by systematic integration of genomics and literature data. First, based on 107 high-quality genome-wide R-loop mapping datasets generated by 11 different technologies, we present a reference set of human R-loop zones for high-confidence R-loop localization, and spot conservative genomic features associated with R-loop formation. Second, through literature mining and multi-omics analyses, we curate the most comprehensive list of R-loop regulatory proteins and their targeted R-loops in multiple species to date. These efforts help reveal a global regulatory network of R-loop dynamics and its potential links to the development of cancers and neurological diseases. Finally, we integrate billions of functional genomic annotations, and develop interactive interfaces to search, visualize, download and analyze R-loops and R-loop regulators in a well-annotated genomic context. R-loopBase allows all users, including those with little bioinformatics background to utilize these data for their own research. We anticipate R-loopBase will become a one-stop resource for the R-loop community.