bluuebunny/crossref_metadata_2025 huggingface dataset:
Karrikin signalling: impacts on plant development and abiotic stress tolerance
Authors: Kamran Muhammad , Melville Kim T , Waters Mark T
Published: November 2023

Plants rely upon a diverse range of metabolites to control growth and development, and to overcome stress that results from suboptimal conditions. Karrikins (KARs) are a class of butenolide compounds found in smoke that stimulate seed germination and regulate various developmental processes in plants. KARs are perceived via a plant α/β-hydrolase called KARRIKIN INSENSITIVE2 (KAI2), which also functions as a receptor for a postulated phytohormone, provisionally termed KAI2 ligand (KL). Considered natural analogues of KL, KARs have been extensively studied for their effects on plant growth and their crosstalk with plant hormones. The perception and response pathway for KAR–KL signalling is closely related to that of strigolactones, another class of butenolides with numerous functions in regulating plant growth. KAR–KL signalling influences seed germination, seedling photomorphogenesis, root system architecture, abiotic stress responses, and arbuscular mycorrhizal symbiosis. Here, we summarize current knowledge of KAR–KL signalling, focusing on its role in plant development, its effects on stress tolerance, and its interaction with other signalling mechanisms.
Image classification for historical documents: a study on Chinese local gazetteers
Authors: Chen Jhe-An , Hou Jen-Chien , Tsai Richard Tzong-Han , Liao Hsiung-Ming , Chen Shih-Pei , Chang Ming-Ching
Published: November 2023

We present a novel approach for automatically classifying illustrations from historical Chinese local gazetteers using modern deep learning techniques. Our goal is to facilitate the digital organization and study of a large quantity of digitized local gazetteers. We evaluate the performance of eight state-of-the-art deep neural networks on a dataset of 4,309 manually labeled and organized images of Chinese local gazetteer illustrations, grouped into three coarse categories and nine fine classes according to their contents. Our experiments show that DaViT achieved the highest classification accuracy of 93.9 per cent and F1-score of 90.6 per cent. Our results demonstrate the effectiveness of deep learning models in accurately recognizing and categorizing historical local gazetteer illustrations. We also developed a user-friendly web service to enable researchers easy access to the developed models. The potential for extending this method to other collections of scanned documents beyond Chinese local gazetteers makes a significant contribution to the study of visual materials in the arts and history in the digital humanities field. The dataset used in this study is publicly available and can be used for further research in the field.
Module 3: Identifying and Understanding your Emotions after Covid-19
Authors: Jaywant Abhishek , Oberlin Lauren E. , Cherestal Stephanie , Bueno Castellano Christina , Wilkins Victoria M. , Kanellopoulos Dora
Published: November 2023

This chapter provides a framework for identifying emotions and becoming more aware of them when they occur. Emotions are an important part of being human, especially when they direct attention to important internal and external events and help inform and guide behavior. However, people with persistent COVID-19 symptoms may have difficulty understanding their emotions, which then could intensify their feelings of distress and discomfort. Learning to recognize and validate emotions can reduce the intensity of difficult emotions and improve the client’s coping. Worksheets in this chapter focus on identifying emotions, myths, and unhelpful judgments. The importance of home practice is emphasized.
Module 7: Reframing Unhelpful Thoughts
Authors: Jaywant Abhishek , Oberlin Lauren E. , Cherestal Stephanie , Bueno Castellano Christina , Wilkins Victoria M. , Kanellopoulos Dora
Published: November 2023

This chapter covers how clients with persistent COVID-19 symptoms can learn to reframe automatic thoughts that contribute to difficult emotions and behaviors that are not beneficial in the long term. Unhelpful thoughts often contain thinking traps in which the brain automatically interprets an ambiguous event as reflecting a worst-case scenario without considering alternative results. Reframing these automatic thoughts can help shift perspectives so that the client takes into account the full context of the situation, thus reducing feelings of anxiety or depression. Worksheets are provided so the client can record automatic thoughts, highlighting the importance of self-validation and acknowledging the uncertainty of the situation.
Module 9: Managing Cognitive Difficulties and “Brain Fog”
Authors: Jaywant Abhishek , Oberlin Lauren E. , Cherestal Stephanie , Bueno Castellano Christina , Wilkins Victoria M. , Kanellopoulos Dora
Published: November 2023

This chapter details several skills to address cognitive difficulties people have after contracting COVID-19. It also introduces the concept of brain fog. After becoming ill with COVID-19, some people report feeling as if their thinking has slowed down, while others have difficulty in focusing and multitasking. Unhelpful thoughts and distressing emotions in reaction to cognitive difficulties can interfere with thinking and make it harder to concentrate, process information, and remember. The chapter offers strategies that may help with cognitive difficulties and brain fog symptoms, such as creating a task list or making environmental modifications. Home practice can increase the effectiveness of cognitive strategies.
Module 11: Participating in Medical Treatment
Authors: Jaywant Abhishek , Oberlin Lauren E. , Cherestal Stephanie , Bueno Castellano Christina , Wilkins Victoria M. , Kanellopoulos Dora
Published: November 2023

This chapter covers the importance of adherence to medical treatment for clients who have persistent COVID-19 symptoms. Adherence to medical and rehabilitation recommendations can improve clients’ daily functioning, reduce disability, and help them return to a more independent and satisfying life. However, multiple barriers and obstacles can make it difficult for individuals to engage in medical care, such as insurance and transportation issues, the cost of treatment and medications, and the evolving healthcare system. Anxiety, depression, hopelessness, and other uncomfortable emotions can also have a major impact on participation in medical treatment. Other topics discussed in this chapter are how to prepare for medical appointments and telehealth visits.
Module 12: Putting it all Together and Managing Uncertainty
Authors: Jaywant Abhishek , Oberlin Lauren E. , Cherestal Stephanie , Bueno Castellano Christina , Wilkins Victoria M. , Kanellopoulos Dora
Published: November 2023

This chapter explores ways that clients can put together and maintain the skills they learned in this treatment program. The key to sustaining gains over time is continuous practice of the skills and techniques learned in therapy. Practicing can help clients to manage ongoing uncertainty about COVID-19 symptoms, navigate setbacks, and prevent relapse into unhealthy cognitive and behavioral patterns. Habit-forming strategies to maintain skills over time include establishing a routine, rewarding oneself, and modifying the environment. The chapter also explains the difference between temporary setbacks (which are inevitable) and the persistent re-emergence of mood or anxiety symptoms (which need further treatment).
Narrow-line Seyfert 1 galaxies in Sloan Digital Sky Survey: a new optical spectroscopic catalogue
Authors: Paliya Vaidehi S , Stalin C S , Domínguez Alberto , Saikia D J
Published: November 2023

Narrow-line Seyfert 1 (NLSy1) galaxies are an enigmatic class of active galactic nuclei (AGN) that exhibit peculiar multiwavelength properties across the electromagnetic spectrum. For example, these sources have allowed us to explore the innermost regions of the central engine of AGN using X-ray observations and have also provided clues about the origin of relativistic jets considering radio and gamma-ray bands. Keeping in mind the ongoing and upcoming wide-field, multifrequency sky surveys, we present a new catalogue of NLSy1 galaxies. This was done by carrying out a detailed decomposition of >2 million optical spectra of quasars and galaxies from the Sloan Digital Sky Survey Data Release 17 (SDSS-DR17) using the publicly available software ‘Bayesian AGN Decomposition Analysis for SDSS Spectra’. The catalogue contains 22656 NLSy1 galaxies which is more than twice the size of the previously identified NLSy1s based on SDSS-DR12. As a corollary, we also release a new catalogue of 52273 broad-line Seyfert 1 (BLSy1) galaxies. The estimated optical spectral parameters and derived quantities confirm the previously known finding of NLSy1 galaxies being AGN powered by highly accreting, low-mass black holes. We conclude that this enlarged sample of NLSy1 and BLSy1 galaxies will enable us to explore the low-luminosity end of the AGN population by effectively utilizing the sensitive, high-quality observations delivered by ongoing/upcoming wide-field sky surveys. The catalogue has been made public at https://www.ucm.es/blazars/seyfert.
The formation of bars and warps in rotating haloes
Authors: Joshi Robin , Widrow Lawrence M
Published: November 2023

We investigate the effects of halo kinematics on the dynamics of stellar discs by simulating the evolution of isolated disc–halo systems from equilibrium initial conditions. Our main results come from four simulations where the initial disc is identical and the halo is either treated as a rigid potential or is ‘live’ with isotropic orbits or orbits that preferentially rotate with or counter to the disc. We confirm previous results that bar formation is more vigorous in models with a live halo than a rigid one and is further enhanced when halo orbits preferentially rotate with the disc. We discuss two types of buckling events with different symmetries about the mid-plane, one that occurs just as the bar is forming and the other well after the bar has been established. We also show that warps are most easily excited and maintained when the halo is counter-rotating with the disc, in agreement with theoretical predictions. Our most novel result is the discovery of a rotating halo instability, which causes the disc and halo cusp to spiral outward from the centre-of-mass of the system whether the halo rotates with the disc or counter to it and also occurs in a disc–bulge–halo system that does not form a bar. We provide a heuristic linear model that captures the essential dynamics of the instability.
Supercoiling-dependent DNA binding: quantitative modeling and applications to bulk and single-molecule experiments
Authors: Kolbeck Pauline J , Tišma Miloš , Analikwu Brian T , Vanderlinden Willem , Dekker Cees , Lipfert Jan
Published: November 2023

DNA stores our genetic information and is ubiquitous in applications, where it interacts with binding partners ranging from small molecules to large macromolecular complexes. Binding is modulated by mechanical strains in the molecule and can change local DNA structure. Frequently, DNA occurs in closed topological forms where topology and supercoiling add a global constraint to the interplay of binding-induced deformations and strain-modulated binding. Here, we present a quantitative model with a straight-forward numerical implementation of how the global constraints introduced by DNA topology modulate binding. We focus on fluorescent intercalators, which unwind DNA and enable direct quantification via fluorescence detection. Our model correctly describes bulk experiments using plasmids with different starting topologies, different intercalators, and over a broad range of intercalator and DNA concentrations. We demonstrate and quantitatively model supercoiling-dependent binding in a single-molecule assay, where we directly observe the different intercalator densities going from supercoiled to nicked DNA. The single-molecule assay provides direct access to binding kinetics and DNA supercoil dynamics. Our model has broad implications for the detection and quantification of DNA, including the use of psoralen for UV-induced DNA crosslinking to quantify torsional tension in vivo, and for the modulation of DNA binding in cellular contexts.
The SysteMHC Atlas v2.0, an updated resource for mass spectrometry-based immunopeptidomics
Authors: Huang Xiaoxiang , Gan Ziao , Cui Haowei , Lan Tian , Liu Yansheng , Caron Etienne , Shao Wenguang
Published: November 2023

The SysteMHC Atlas v1.0 was the first public repository dedicated to mass spectrometry-based immunopeptidomics. Here we introduce a newly released version of the SysteMHC Atlas v2.0 (https://systemhc.sjtu.edu.cn), a comprehensive collection of 7190 MS files from 303 allotypes. We extended and optimized a computational pipeline that allows the identification of MHC-bound peptides carrying on unexpected post-translational modifications (PTMs), thereby resulting in 471K modified peptides identified over 60 distinct PTM types. In total, we identified approximately 1.0 million and 1.1 million unique peptides for MHC class I and class II immunopeptidomes, respectively, indicating a 6.8-fold increase and a 28-fold increase to those in v1.0. The SysteMHC Atlas v2.0 introduces several new features, including the inclusion of non-UniProt peptides, and the incorporation of several novel computational tools for FDR estimation, binding affinity prediction and motif deconvolution. Additionally, we enhanced the user interface, upgraded website framework, and provided external links to other resources related. Finally, we built and provided various spectral libraries as community resources for data mining and future immunopeptidomic and proteomic analysis. We believe that the SysteMHC Atlas v2.0 is a unique resource to provide key insights to the immunology and proteomics community and will accelerate the development of vaccines and immunotherapies.
Quantification and modeling of turnover dynamics of de novo transcripts in Drosophila melanogaster
Authors: Grandchamp Anna , Czuppon Peter , Bornberg-Bauer Erich
Published: November 2023

Most of the transcribed eukaryotic genomes are composed of non-coding transcripts. Among these transcripts, some are newly transcribed when compared to outgroups and are referred to as de novo transcripts. De novo transcripts have been shown to play a major role in genomic innovations. However, little is known about the rates at which de novo transcripts are gained and lost in individuals of the same species. Here, we address this gap and estimate the de novo transcript turnover rate with an evolutionary model. We use DNA long reads and RNA short reads from seven geographically remote samples of inbred individuals of Drosophila melanogaster to detect de novo transcripts that are gained on a short evolutionary time scale. Overall, each sampled individual contains around 2500 unspliced de novo transcripts, with most of them being sample specific. We estimate that around 0.15 transcripts are gained per year, and that each gained transcript is lost at a rate around 5× 10−5 per year. This high turnover of transcripts suggests frequent exploration of new genomic sequences within species. These rate estimates are essential to comprehend the process and timescale of de novo gene birth.
The Monarch Initiative in 2024: an analytic platform integrating phenotypes, genes and diseases across species
Authors: Putman Tim E , Schaper Kevin , Matentzoglu Nicolas , Rubinetti Vincent P , Alquaddoomi Faisal S , Cox Corey , Caufield J Harry , Elsarboukh Glass , Gehrke Sarah , Hegde Harshad , Reese Justin T , Braun Ian , Bruskiewich Richard M , Cappelletti Luca , Carbon Seth , Caron Anita R , Chan Lauren E , Chute Christopher G , Cortes Katherina G , De Souza Vinícius , Fontana Tommaso , Harris Nomi L , Hartley Emily L , Hurwitz Eric , Jacobsen Julius O B , Krishnamurthy Madan , Laraway Bryan J , McLaughlin James A , McMurry Julie A , Moxon Sierra A T , Mullen Kathleen R , O’Neil Shawn T , Shefchek Kent A , Stefancsik Ray , Toro Sabrina , Vasilevsky Nicole A , Walls Ramona L , Whetzel Patricia L , Osumi-Sutherland David , Smedley Damian , Robinson Peter N , Mungall Christopher J , Haendel Melissa A , Munoz-Torres Monica C
Published: November 2023

Bridging the gap between genetic variations, environmental determinants, and phenotypic outcomes is critical for supporting clinical diagnosis and understanding mechanisms of diseases. It requires integrating open data at a global scale. The Monarch Initiative advances these goals by developing open ontologies, semantic data models, and knowledge graphs for translational research. The Monarch App is an integrated platform combining data about genes, phenotypes, and diseases across species. Monarch's APIs enable access to carefully curated datasets and advanced analysis tools that support the understanding and diagnosis of disease for diverse applications such as variant prioritization, deep phenotyping, and patient profile-matching. We have migrated our system into a scalable, cloud-based infrastructure; simplified Monarch's data ingestion and knowledge graph integration systems; enhanced data mapping and integration standards; and developed a new user interface with novel search and graph navigation features. Furthermore, we advanced Monarch's analytic tools by developing a customized plugin for OpenAI’s ChatGPT to increase the reliability of its responses about phenotypic data, allowing us to interrogate the knowledge in the Monarch graph using state-of-the-art Large Language Models. The resources of the Monarch Initiative can be found at monarchinitiative.org and its corresponding code repository at github.com/monarch-initiative/monarch-app.
GproteinDb in 2024: new G protein-GPCR couplings, AlphaFold2-multimer models and interface interactions
Authors: Pándy-Szekeres Gáspár , Taracena Herrera Luis P , Caroli Jimmy , Kermani Ali A , Kulkarni Yashraj , Keserű György M , Gloriam David E
Published: November 2023

G proteins are the major signal proteins of ∼800 receptors for medicines, hormones, neurotransmitters, tastants and odorants. GproteinDb offers integrated genomic, structural, and pharmacological data and tools for analysis, visualization and experiment design. Here, we present the first major update of GproteinDb greatly expanding its coupling data and structural templates, adding AlphaFold2 structure models of GPCR–G protein complexes and advancing the interactive analysis tools for their interfaces underlying coupling selectivity. We present insights on coupling agreement across datasets and parameters, including constitutive activity, agonist-induced activity and kinetics. GproteinDb is accessible at https://gproteindb.org.
RPA guides UNG to uracil in ssDNA to facilitate antibody class switching and repair of mutagenic uracil at the replication fork
Authors: Hayran Abdul B , Liabakk Nina B , Aas Per A , Kusnierczyk Anna , Vågbø Cathrine B , Sarno Antonio , Iveland Tobias S , Chawla Konika , Zahn Astrid , Di Noia Javier M , Slupphaug Geir , Kavli Bodil
Published: November 2023

Activation-induced cytidine deaminase (AID) interacts with replication protein A (RPA), the major ssDNA-binding protein, to promote deamination of cytosine to uracil in transcribed immunoglobulin (Ig) genes. Uracil-DNA glycosylase (UNG) acts in concert with AID during Ig diversification. In addition, UNG preserves genome integrity by base-excision repair (BER) in the overall genome. How UNG is regulated to support both mutagenic processing and error-free repair remains unknown. UNG is expressed as two isoforms, UNG1 and UNG2, which both contain an RPA-binding helix that facilitates uracil excision from RPA-coated ssDNA. However, the impact of this interaction in antibody diversification and genome maintenance has not been investigated. Here, we generated B-cell clones with targeted mutations in the UNG RPA-binding motif, and analysed class switch recombination (CSR), mutation frequency (5′ Ig Sμ), and genomic uracil in clones representing seven Ung genotypes. We show that the UNG:RPA interaction plays a crucial role in both CSR and repair of AID-induced uracil at the Ig loci. By contrast, the interaction had no significant impact on total genomic uracil levels. Thus, RPA coordinates UNG during CSR and pre-replicative repair of mutagenic uracil in ssDNA but is not essential in post-replicative and canonical BER of uracil in dsDNA.
Cyclic di-GMP inhibits nitrate assimilation by impairing the antitermination function of NasT in Pseudomonas putida
Authors: Nie Liang , Xiao Yujie , Zhou Tiantian , Feng Haoqi , He Meina , Liang Qingyuan , Mu Kexin , Nie Hailing , Huang Qiaoyun , Chen Wenli
Published: November 2023

The ubiquitous bacterial second messenger cyclic diguanylate (c-di-GMP) coordinates diverse cellular processes through its downstream receptors. However, whether c-di-GMP participates in regulating nitrate assimilation is unclear. Here, we found that NasT, an antiterminator involved in nitrate assimilation in Pseudomonas putida, specifically bound c-di-GMP. NasT was essential for expressing the nirBD operon encoding nitrite reductase during nitrate assimilation. High-level c-di-GMP inhibited the binding of NasT to the leading RNA of nirBD operon (NalA), thus attenuating the antitermination function of NasT, resulting in decreased nirBD expression and nitrite reductase activity, which in turn led to increased nitrite accumulation in cells and its export. Molecular docking and point mutation assays revealed five residues in NasT (R70, Q72, D123, K127 and R140) involved in c-di-GMP-binding, of which R140 was essential for both c-di-GMP-binding and NalA-binding. Three diguanylate cyclases (c-di-GMP synthetases) were found to interact with NasT and inhibited nirBD expression, including WspR, PP_2557, and PP_4405. Besides, the c-di-GMP-binding ability of NasT was conserved in the other three representative Pseudomonas species, including P. aeruginosa, P. fluorescens and P. syringae. Our findings provide new insights into nitrate assimilation regulation by revealing the mechanism by which c-di-GMP inhibits nitrate assimilation via NasT.
Co-transcriptional folding of the glmS ribozyme enables a rapid response to metabolite
Authors: Lou Yuan , Woodson Sarah A
Published: November 2023

The glmS ribozyme riboswitch, located in the 5′ untranslated region of the Bacillus subtilis glmS messenger RNA (mRNA), regulates cell wall biosynthesis through ligand-induced self-cleavage and decay of the glmS mRNA. Although self-cleavage of the refolded glmS ribozyme has been studied extensively, it is not known how early the ribozyme folds and self-cleaves during transcription. Here, we combine single-molecule fluorescence with kinetic modeling to show that self-cleavage can occur during transcription before the ribozyme is fully synthesized. Moreover, co-transcriptional folding of the RNA at a physiological elongation rate allows the ribozyme catalytic core to react without the downstream peripheral stability domain. Dimethyl sulfate footprinting further revealed how slow sequential folding favors formation of the native core structure through fraying of misfolded helices and nucleation of a native pseudoknot. Ribozyme self-cleavage at an early stage of transcription may benefit glmS regulation in B. subtilis, as it exposes the mRNA to exoribonuclease before translation of the open reading frame can begin. Our results emphasize the importance of co-transcriptional folding of RNA tertiary structure for cis-regulation of mRNA stability.
RNA-binding protein Nocte regulates Drosophila development by promoting translation reinitiation on mRNAs with long upstream open reading frames
Authors: Zhang Tianyi , Xue Yutong , Su Shuaikun , Altouma Valerie , Ho Katherine , Martindale Jennifer L , Lee Seung-Kyu , Shen Weiping , Park Aaron , Zhang Yongqing , De Supriyo , Gorospe Myriam , Wang Weidong
Published: November 2023

RNA-binding proteins (RBPs) with intrinsically disordered regions (IDRs) are linked to multiple human disorders, but their mechanisms of action remain unclear. Here, we report that one such protein, Nocte, is essential for Drosophila eye development by regulating a critical gene expression cascade at translational level. Knockout of nocte in flies leads to lethality, and its eye-specific depletion impairs eye size and morphology. Nocte preferentially enhances translation of mRNAs with long upstream open reading frames (uORFs). One of the key Nocte targets, glass mRNA, encodes a transcription factor critical for differentiation of photoreceptor neurons and accessory cells, and re-expression of Glass largely rescued the eye defects caused by Nocte depletion. Mechanistically, Nocte counteracts long uORF-mediated translational suppression by promoting translation reinitiation downstream of the uORF. Nocte interacts with translation factors eIF3 and Rack1 through its BAT2 domain, and a Nocte mutant lacking this domain fails to promote translation of glass mRNA. Notably, de novo mutations of human orthologs of Nocte have been detected in schizophrenia patients. Our data suggest that Nocte family of proteins can promote translation reinitiation to overcome long uORFs-mediated translational suppression, and disruption of this function can lead to developmental defects and neurological disorders.
Oxygen saturation in healthy-term neonates at high altitude: A multisite prospective study
Authors: Kannan Loganathan Prakash , Nettel-Aguirre Alberto , Lodha Abhay , Al Awad Essa , Fajardo Carlos , Nair Vrinda , Scotland Jeanne , Singhal Nalini , Young Marilyn , York Kristin , Rabi Yacov
Published: November 2023

Objectives

To determine oxygen saturation (SpO2) values and their variability in healthy-term neonates at high altitude.

Methods

In a prospective multisite, non-randomized blinded study, we performed SpO2 measurements in healthy neonates admitted to postnatal wards and followed up in Public Health Nurse Clinics (PHNC) in Calgary, Alberta, Canada. We recruited healthy-term neonates (≥37 weeks) between 6 and 24 h of age. Neonates underwent simultaneous pre- and post-ductal SpO2 recordings every 12 to 24 h until hospital discharge and again in the PHNC within a few days after discharge. Neonates were followed for 8 weeks to ascertain their health status.

Results

We included data for 252 neonates in hospital and 105 neonates presenting to the PHNC for follow-up. In hospital, the mean pre- and post-ductal SpO2 were 94.3% and 96.0%, respectively. In the PHNC, mean pre- and post-ductal SpO2 were 94.4% and 95.6%, respectively. Desaturation episodes occurred frequently at a median rate of once every 5 minutes. The median duration of pre-ductal desaturation episodes was longer in hospital than in the PHNC for all SpO2 thresholds (P < 0.05).

Conclusion

SpO2 levels in healthy-term neonates at high altitude are approximately 94% and remained stable over the first few days after birth. Desaturation episodes are common in the immediate neonatal period, but their duration decreases over time, and they are not associated with clinical deterioration.

Clinic trials.org (NCT 02095041).
Improved super-resolution ribosome profiling reveals prevalent translation of upstream ORFs and small ORFs in Arabidopsis
Authors: Wu Hsin-Yen Larry , Ai Qiaoyun , Teixeira Rita Teresa , Nguyen Phong H T , Song Gaoyuan , Montes Christian , Elmore J Mitch , Walley Justin W , Hsu Polly Yingshan
Published: November 2023

A crucial step in functional genomics is identifying actively translated ORFs and linking them to biological functions. The challenge lies in identifying short ORFs, as their identification is greatly influenced by data quality and depth. Here, we improved the coverage of super-resolution Ribo-seq in Arabidopsis (Arabidopsis thaliana), revealing uncharacterized translation events for nuclear, chloroplastic, and mitochondrial genes. Assisted by a transcriptome assembly, we identified 7,751 unconventional translation events, comprising 6,996 upstream ORFs (uORFs) and 209 downstream ORFs on annotated protein-coding genes, as well as 546 ORFs in presumed noncoding RNAs. Proteomic data confirmed the production of stable proteins from some of these unannotated translation events. We present evidence of active translation from primary transcripts of trans-acting small interfering RNAs (TAS1–4) and microRNAs (pri-MIR163 and pri-MIR169) and periodic ribosome stalling supporting cotranslational decay. Additionally, we developed a method for identifying extremely short uORFs, including 370 minimum uORFs (AUG-stop), and 2,921 tiny uORFs (2 to 10 amino acids) and 681 uORFs that overlap with each other. Remarkably, these short uORFs exhibit strong translational repression as do longer uORFs. We also systematically discovered 594 uORFs regulated by alternative splicing, suggesting widespread isoform-specific translational control. Finally, these prevalent uORFs are associated with numerous important pathways. In summary, our improved Arabidopsis translational landscape provides valuable resources to study gene expression regulation.
Conservation of the moss RNA editing factor PPR78 despite the loss of its known cytidine-to-uridine editing sites is explained by a hidden extra target
Authors: Lesch Elena , Stempel Maike Simone , Dressnandt Vanessa , Oldenkott Bastian , Knoop Volker , Schallenberg-Rüdinger Mareike
Published: November 2023

Cytidine (C)-to-uridine (U) RNA editing in plant organelles relies on specific RNA-binding pentatricopeptide repeat (PPR) proteins. In the moss Physcomitrium patens, all such RNA editing factors feature a C-terminal DYW domain that acts as the cytidine deaminase for C-to-U conversion. PPR78 of Physcomitrium targets 2 mitochondrial editing sites, cox1eU755SL and rps14eU137SL. Remarkably, the latter is edited to highly variable degrees in different mosses. Here, we aimed to unravel the coevolution of PPR78 and its 2 target sites in mosses. Heterologous complementation in a Physcomitrium knockout line revealed that the variable editing of rps14eU137SL depends on the PPR arrays of different PPR78 orthologues but not their C-terminal domains. Intriguingly, PPR78 has remained conserved despite the simultaneous loss of editing at both known targets among Hypnales (feather mosses), suggesting it serves an additional function. Using a recently established RNA editing assay in Escherichia coli, we confirmed site-specific RNA editing by PPR78 in the bacterium and identified 4 additional off-targets in the bacterial transcriptome. Based on conservation profiles, we predicted ccmFNeU1465RC as a candidate editing target of PPR78 in moss mitochondrial transcriptomes. We confirmed editing at this site in several mosses and verified that PPR78 targets ccmFNeU1465RC in the bacterial editing system, explaining the conservation and functional adaptation of PPR78 during moss evolution.
Long-term outcomes of lupus nephritis with low-level proteinuria: a multicentre, retrospective study
Authors: Zoshima Takeshi , Hara Satoshi , Suzuki Kazuyuki , Yoshida Misaki , Konishi Masahiro , Hibino Shinya , Suda Takuya , Hoshiba Ryohei , Kawahara Hiroyuki , Horita Shigeto , Nuka Hiromi , Mizushima Ichiro , Kawano Mitsuhiro
Published: November 2023

Objectives

Reportedly, patients with LN and low-level proteinuria have favourable short-term renal outcomes. We aimed to clarify the long-term renal outcomes and overall survival of these patients, and the significance of renal biopsy in the early phase with low-level proteinuria.

Methods

We included 144 Japanese patients with biopsy-proven LN from 10 hospitals. Low-level proteinuria was defined by a urine protein:creatinine ratio (UPCR) of ≤1 g/gCr based on previous reports. The outcomes were end-stage renal disease (ESRD) and death.

Results

Compared with patients with high-level proteinuria (UPCR >1 g/gCr), those with low-level proteinuria [n = 67 (46.5%)] had significantly improved renal function at the time of renal biopsy, and low activity index and chronicity index while the frequency of class III/IV was similar (79.1% vs 84.4%, P = 0.409). In patients with low-level proteinuria, CYC usage was less, and the incidences of ESRD (3.0% vs 13.0%, P = 0.036) and death (3.0% vs 16.9%, P = 0.006) during the total observation period (median, 72 months) were low. Kaplan–Meier analysis showed significant differences in the incidence of ESRD and death between the groups. Multivariate Cox regression analysis revealed that the significant risk factors for ESRD were high chronicity index and hypertension, whereas those for death were increased age and high-level proteinuria.

Conclusion

Patients with LN and low-level proteinuria had favourable long-term renal and life outcomes. As these patients have substantial active pathological lesions, renal biopsy in the early phase with low-level proteinuria could enable early diagnosis and treatment and thus improve prognosis.
Genetic testing of Behçet’s disease using next-generation sequencing to identify monogenic mimics and HLA-B*51
Authors: Burleigh Alice , Omoyinmi Ebun , Papadopoulou Charalampia , Al-Abadi Eslam , Hong Ying , Price-Kuehne Fiona , Moraitis Elena , Titheradge Hannah , Montesi Francesca , Xu Diane , Eleftheriou Despina , Brogan Paul
Published: November 2023

Objective

Several monogenic autoinflammatory disorders and primary immunodeficiencies can present early in life with features that may be mistaken for Behçet’s disease (BD). We aimed to develop a genetic analysis workflow to identify rare monogenic BD-like diseases and establish the contribution of HLA haplotype in a cohort of patients from the UK.

Methods

Patients with clinically suspected BD were recruited from four BD specialist care centres in the UK. All participants underwent whole-exome sequencing (WES), and genetic analysis thereafter by (i) examining genes known to cause monogenic immunodeficiency, autoinflammation or vasculitis by virtual panel application; (ii) scrutiny of variants prioritized by Exomiser using Human Phenotype Ontology (HPO); (iii) identification of copy number variants using ExomeDepth; and (iv) HLA-typing using OptiType.

Results

Thirty-one patients were recruited: median age 15 (4–52), and median disease onset age 5 (0–20). Nine/31 (29%) patients had monogenic disease mimicking BD: five cases of Haploinsufficiency of A20 with novel TNFAIP3 variants (p.T76I, p. M112Tfs*8, p. S548Dfs*128, p. C657Vfs*14, p. E661Nfs*36); one case of ISG15 deficiency with a novel nonsense variant (ISG15: p.Q16X) and 1p36.33 microdeletion; one case of common variable immune deficiency (TNFRSF13B: p.A181E); and two cases of TNF receptor-associated periodic syndrome (TNFRSF1A: p.R92Q). Of the remaining 22 patients, eight (36%) were HLA-B*51 positive.

Conclusion

We describe a novel genetic workflow for BD, which can efficiently detect known and potentially novel monogenic forms of BD, whilst additionally providing HLA-typing. Our results highlight the importance of genetic testing before BD diagnosis, as this has an impact on choice of therapy, prognosis and genetic counselling.
The saliency of the CEO pay ratio
Authors: Boone Audra , Starkweather Austin , White Joshua T
Published: November 2023

The US Securities and Exchange Commission’s mandated CEO pay ratio is a simple, but salient, metric that could resonate with employees given it focuses on their compensation. Reporting a relatively or surprisingly high ratio reduces employee perceptions of their pay, views of the CEO, and hampers productivity growth. Employee pay satisfaction drops after disclosing a high ratio even if their wages were previously disclosed and when the pay ratio disclosure adds little new information. Disclosures by firms with a high ratio contain more discretionary language to explain the ratio or portray employee relations positively and are more likely to be covered by the media. However, neither information source substantially alters the employee response to a salient ratio. Our work illustrates that requiring firms to disclose a salient metric can have unintended consequences on employees and suggests caution in requiring firms to report simplified Environmental, Social, and Governance (ESG) metrics that are inherently multifaceted.
Israel—estate planning for the unwary
Authors: Eyal Lyat
Published: November 2023

The importance of estate planning cannot be emphasized enough, so much more so where the relevant individuals have a connection to more than one jurisdiction. Said connection may be with respect to citizenship, residency, ownership of assets or the jurisdiction of residence of the heirs. This article considers each of these factors separately. As the world is global, more individuals are affected by the laws of foreign jurisdictions upon their demise and if no planning has been effected during their lifetime, the heirs are left to clean up the mess.
Implications of the COVID-19 trajectory for the evaluation of hand hygiene interventions: Secondary analysis of the Soapp trial
Authors: Baretta Dario , Inauen Jennifer
Published: November 2023

Hand hygiene behavior is crucial to counter the spread of infectious diseases. However, its adoption during the early stages of the Coronavirus disease (COVID-19) pandemic showed temporal fluctuations associated with the trajectory of the pandemic (e.g. new COVID-19 infections). Such associations can confound conclusions about the effectiveness of interventions aimed at promoting hand hygiene during a pandemic. In this study, we performed a secondary analysis of a dataset from the optimization phase of Soapp, an app to promote hand hygiene during the COVID-19 pandemic. We used a longitudinal study design to test whether the associations between the pandemic trajectory and hand hygiene behavior were still present one year after the outbreak (primary outcome) and whether they impacted conclusions about the effectiveness of Soapp (secondary outcome). Participants (N = 216) were randomized to different versions of Soapp and used an electronic diary to self-report their hand hygiene behavior multiple times during the study. We considered the following indicators of the COVID-19 pandemic from the country of Switzerland in the period between March and August 2021: total cases/deaths, increases in recent new cases/deaths, new cases/deaths, and number of administered doses of vaccine. Data were analyzed using a multilevel approach. Results suggested that there were no significant associations between hand hygiene and the indicators of the pandemic trajectory. However, models including total cases/deaths impacted the conclusions about Soapp’s effectiveness. Implications from this study are that the development and evaluation of hand hygiene interventions during a pandemic context should account for the trajectory indicators to maximize their effectiveness and control for confounding effects.
LINC02454 promotes thyroid carcinoma progression via upregulating HMGA2 through CREB1
Authors: Cao Yan , Li Jian , Du Yongliang , Sun Yuxuan , Liu Le , Fang Hao , Liang Yan , Mao Shanshan
Published: November 2023

Thyroid carcinoma (THCA) is the most common malignancy in the endocrine system. Long intergenic non‐coding RNA 2454 (LINC02454) exhibits an HMGA2‐like expression pattern, but their relationship and roles in THCA are largely unknown. The present purpose was to delineate the roles of LINC02454 in THCA progression and its molecular mechanisms. We collected THCA tissues from patients and monitored patient survival. THCA cell colony formation, migration, and invasion were evaluated. Metastasis was evaluated by examining EMT markers through Western blotting. Gene interaction was determined with ChIP, RIP, RNA pull‐down, and luciferase activity assays. A mouse model of a subcutaneous tumor was used to determine the activity of LINC02454 knockdown in vivo. We found that LINC02454 was highly expressed in THCA, and its upregulation was associated with poor survival. The knockdown of LINC02454 repressed colony formation, migration, and invasion. Moreover, loss of LINC02454 inhibited tumor growth and metastasis in mice. HMGA2 promoted LINC02454 transcription via binding to the LINC02454 promoter, and silencing of HMGA2 suppressed malignant behaviors through downregulation of LINC02454. HMGA2 was a novel functional target of LINC02454 in THCA cells, and knockdown of LINC02454‐mediated anti‐tumor effects was reversed by HMGA2 overexpression. Mechanically, LINC02454 promoted CREB1 phosphorylation and nuclear translocation, and CREB1 was subsequently bound to the HMGA2 promoter to facilitate its expression. LINC02454 cis‐regulates HMGA2 transcription via facilitating CREB1 phosphorylation and nuclear translocation, and, in turn, HMGA2 promotes LINC02454 expression, thus accelerating thyroid carcinoma progression. Our results support therapeutic targets of LINC02454 and HMGA2 for THCA.
Phase-amplitude coupling of NREM sleep oscillations is unaffected by pre-sleep learning but related to overnight memory gains depending on the declarative learning paradigm
Authors: Cross Nathan , O’Byrne Jordan , Weiner Oren M. , Giraud Julia , Perrault Aurore A. , Dang-Vu Thien Thanh
Published: November 2023

There is growing evidence in humans linking the temporal coupling between spindles and slow oscillations during NREM sleep with the overnight stabilization of memories encoded from daytime experiences in humans. However, whether the type and strength of learning influence that relationship is still unknown. Here we tested whether the amount or type of verbal word-pair learning prior to sleep affects subsequent phase-amplitude coupling (PAC) between spindles and slow oscillations (SO). We measured the strength and preferred timing of such coupling in the EEG of 41 healthy human participants over a post-learning and control night, to compare intra-individual changes with inter-individual differences. We leveraged learning paradigms of varying word-pair (WP) load: 40 WP learned to a minimum criterion of 60% correct (n=11); 40 WP presented twice (n=15); 120 WP presented twice (n=15). There were no significant differences in the preferred phase or strength between the control and post-learning nights, in all learning conditions. We observed an overnight consolidation effect (improved performance at delayed recall) for the criterion learning condition only, and only in this condition was the overnight change in memory performance significantly positively correlated with the phase of SO-spindle coupling. These results suggest that the coupling of brain oscillations during human NREM sleep are stable traits that are not modulated by the amount of pre-sleep learning, yet are implicated in the sleep-dependent consolidation of memory.
Stimulating prefrontal cortex facilitates training transfer by increasing representational overlap
Authors: Wards Yohan , Ehrhardt Shane E. , Filmer Hannah L. , Mattingley Jason B. , Garner Kelly G. , Dux Paul E.
Published: November 2023

Difficulties in multitasking may be the price humans pay for our ability to generalise learning to new tasks. Mitigating these costs through training has been associated with reduced overlap of constituent task representations within a task-related brain network. Transcranial direct current stimulation (tDCS), which can modulate neural activity, has shown promise in generalising training gains. Whether tDCS influences the changes in task-associated representations to produce such training generalisation remains unexplored. Here, we paired prefrontal cortex tDCS with multitasking training, and collected functional magnetic resonance imaging data pre- and post- training. We found that 1mA tDCS enhanced visual search performance, and using machine learning to assess the overlap of brain activity related to the training, show that these generalised gains were predicted by changes in classification accuracy for patterns of frontal, parietal, and cerebellar activity in participants who received left prefrontal cortex stimulation. Thus, prefrontal cortex tDCS interacts with training related changes in task representations, potentially driving the generalisation of learning.
Host signature as major driver of root and rhizosphere core microbiomes that differently affect plant functional traits
Authors: Luo Jipeng , Wang Yuanfan , Zhang Yu , Gao Wenzhe , Liang Yongchao , Zhao He-Ping , Gu Shaohua , Li Tingqiang
Published: November 2023

Background

Plant can evolve with a core root microbiome that maintains essential functions for host performance. However, the relative importance of plant traits and soil factors on the structure, assembly, co-occurrence networks of the core root microbiomes and their relevance for plant characteristics remain elusive. Here, we investigated how plant species identity and soil environment affect the core bacterial communities in the bulk soil, rhizosphere and root endosphere of four plants with a gradient of Cd/Zn accumulation capacity under controlled and field environments. We further tested on the role of the core bacterial isolates in plant growth and accumulation of metal and nutrients.

Results

We identified root compartment and plant species rather than environmental parameters as the primary driver of Cd-accumulator root microbiome. Stochastic processes were more important for the assembly of endosphere generalists (58.5%) than rhizosphere counterparts (45.2%), indicating that generalists were more robust to environmental changes. Increasing host selection from epiphytes to endophytes resulted in the existence of the endosphere and rhizosphere generalist core microbiota common to different plants under varying growth environments, highlighting that shared environmental and physiological features of host plants are decisive for core microbiome establishment. Further, endophytic core microbiota conferred greater biotic connectivity within networks and was more important predictors of plant metal accumulation, whereas the rhizosphere cores were more closely linked to plant biomass and nutrient status. The divergent functions of rhizosphere and endosphere core microbes on plant characteristics were also validated by inoculating the synthetic communities comprising bacterial isolates belonging to the core microbiota.

Conclusion

This study indicated the pivotal role of plant trait in the assembly of conserved and functionally important core microbiome common to different Cd-accumulators, which brings us closer to manipulating the persistent root microbial associations to accelerate the rejuvenation of metal-disturbed soils through host genetics.
ADNP Modulates SINE B2-Derived CTCF-Binding Sites during Blastocyst Formation in Mouse
Authors: Wang Wen , Gao Rui , Yang Dongxu , Ma Mingli , Zang Ruge , Wang Xiangxiu , Chen Chuan , Chen Jiayu , Kou Xiaochen , Zhao Yanhong , Liu Xuelian , Wang Hong , Gao Yawei , Zhang Yong , Gao Shaorong
Published: November 2023

During early embryo development, the nuclear factor CTCF plays a vital role in organizing chromatin structure and regulating transcription. Recent studies have examined the establishment of nucleosome profiles around the CTCF motif sites shortly after fertilization. However, the kinetics of CTCF chromatin occupation in pre-implantation embryos have remained unclear. In this study, we utilized CUT&RUN technology to investigate CTCF occupancy in mouse pre-implantation development. Our findings revealed that CTCF begins binding to the genome prior to zygotic genome activation (ZGA), with a preference for CTCF anchored chromatin loops. Although the majority of CTCF occupancy is consistently maintained, we identified a specific set of binding sites enriched in the mouse-specific short-interspersed element (SINE) family B2, which are restricted to the cleavage stages. Notably, our data suggested that the neuroprotective protein ADNP may counteract the stable association of CTCF at SINE B2-derived CTCF-binding sites.