bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pepper mild mottle virus coat protein interacts with pepper chloroplast outer envelope membrane protein OMP24 to inhibit antiviral immunity in plants
Authors: Han Kelei , Zheng Hongying , Yan Dankan , Zhou Huijie , Jia Zhaoxing , Zhai Yushan , Wu Jian , Lu Yuwen , Wu Guanwei , Rao Shaofei , Chen Jianping , Peng Jiejun , Qi Rende , Yan Fei 
Published: March 2023

AbstractPepper mild mottle virus (PMMoV) is a devastating viral pathogen of pepper (Capsicum annuum) but it is unclear whether and how peppers protect against PMMoV infection. The expression of the chloroplast outer membrane protein 24 (OMP24) of C. annuum was upregulated under PMMoV infection and it interacted with PMMoV coat protein (CP). Silencing of OMP24 in either C. annuum or Nicotiana benthamiana facilitated PMMoV infection, whereas overexpression of N. benthamiana OMP24 in transgenic plants inhibited PMMoV infection. Both C. annuum OMP24 (CaOMP24) and N. benthamiana OMP24 (NbOMP24) localized to the chloroplast and have a moderately hydrophobic transmembrane domain that is necessary for their localization. Overexpression of CaOMP24 induced stromules, perinuclear chloroplast clustering, and accumulation of reactive oxygen species (ROS), the typical defense responses of chloroplasts transferring the retrograde signaling to the nucleus to regulate resistance genes. The expression of PR1 and PR2 was also upregulated significantly in plants overexpressing OMP24. Self-interaction of OMP24 was demonstrated and was required for OMP24-mediated plant defense. Interaction with PMMoV CP interfered with the self-interaction of OMP24 and impaired OMP24-induced stromules, perinuclear chloroplast clustering and ROS accumulation. The results demonstrate the defense function of OMP24 in pepper during viral infection and suggest a possible mechanism by which PMMoV CP modulates the plant defense to facilitate viral infection.
Changes in circulating forms of anti-Muüllerian hormone and androgens in women with and without PCOS: a systematic longitudinal study throughout pregnancy
Authors: Peigné M , Simon V , Pigny P , Mimouni N E H , Martin C , Dewailly D , Catteau-Jonard S , Giacobini P 
Published: March 2023

Abstract

STUDY QUESTION
What are the changes in serum concentration of total and cleaved anti-Muüllerian hormone (AMH) molecular forms and of androgens before and throughout pregnancy in women with and without polycystic ovary syndrome (PCOS) in a longitudinal follow-up investigation?

SUMMARY ANSWER
Serum levels of total and cleaved AMH are higher from preconception to the third trimester of pregnancy in women with PCOS as compared to controls, whereas testosterone and androstenedione levels are higher in women with PCOS than in control women before pregnancy and during the second and third trimester of pregnancy.

WHAT IS KNOWN ALREADY
Cross-sectional or partial longitudinal studies have shown higher AMH and androgen levels in pregnant women with PCOS as compared with non-PCOS women. To date, no complete longitudinal dynamic monitoring of the circulating forms of AMH and androgens from pre-conception to the third trimester of pregnancy have compared women with and without PCOS.

STUDY DESIGN, SIZE, DURATION
This systematic prospective quarterly longitudinal monocentric study was a comparative follow-up of 30 women with PCOS and 29 controls before and during pregnancy from April 2019 to July 2022.

PARTICIPANTS/MATERIALS, SETTING, METHODS
Women aged 18–43 years with a pre-conception measurement of AMH were included during the first trimester of a singleton pregnancy. The PCOS group was defined according to the Rotterdam diagnostic criteria. The control group patients included in the study had normal ovarian reserves. Circulating total and cleaved AMH, and serum estradiol, LH, and androgen levels were measured during the first, second, and third trimester of pregnancy in all study participants.

MAIN RESULTS AND THE ROLE OF CHANCE
Before pregnancy, patients with PCOS had higher levels of AMH than controls. The total and cleaved AMH forms were significantly higher in women with PCOS than controls from pre-conception to the third trimester of pregnancy (all P &lt; 0.001). Androgens (total testosterone and androstenedione) were higher in women with PCOS than controls from mid-pregnancy onwards.

LIMITATIONS, REASONS FOR CAUTION
Our control population was a population of infertile women with no ovarian problems but most of them had undergone ART treatments to achieve pregnancy.

WIDER IMPLICATIONS OF THE FINDINGS
These results strengthen the hypothesis that gestational hyperandrogenism as well as exposure to elevated AMH levels in utero could be driving forces predisposing female progeny to develop PCOS.

STUDY FUNDING/COMPETING INTEREST(S)
Funding was provided by INSERM, France (grant number U1172) and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program, ERC-2016-CoG to P.G. grant agreement n° 725149/REPRODAMH. The authors have nothing to declare.

TRIAL REGISTRATION NUMBER
NCT03483792
Finite element approximation of Hamilton–Jacobi–Bellman equations with nonlinear mixed boundary conditions
Authors: Jaroszkowski Bartosz , Jensen Max 
Published: March 2023

Abstract
We show strong uniform convergence of monotone P1 finite element methods to the viscosity solution of isotropic parabolic Hamilton–Jacobi–Bellman equations with mixed boundary conditions on unstructured meshes and for possibly degenerate diffusions. Boundary operators can generally be discontinuous across face-boundaries and type changes. Robin-type boundary conditions are discretized via a lower Dini derivative. In time, the Bellman equation is approximated through IMEX schemes. Existence and uniqueness of numerical solutions follows through Howard’s algorithm.
Swirling flow analysis of Eyring–Powell fluid between coaxial disks with variable property
Authors: Nadeem Sohail , Ishtiaq Bushra , Akkurt Nevzat , Eldin Sayed M 
Published: March 2023

Abstract
The main objective of this study is to examine an unsteady swirling flow of a non-Newtonian Eyring–Powell fluid between two coaxial disks. The lower and upper disks are considered to rotate with different angular velocities. The three-dimensional axisymmetric flow phenomenon and heat transfer mechanism are observed with the consequences of the magnetic field and variable thermal conductivity of the fluid. The variable thermal conductivity is taken to be dependent on the fluid temperature. The implementation of the Von Karman similarity transformations on the constituting equations of the flow phenomenon yields the dimensionless system of the non-linear equations. An optimal homotopy analysis technique is adopted to obtain analytical solutions for highly non-linear equations. In view of the same and opposite directions of disks rotation, the various aspects of the flow system corresponding to the pertinent parameters are discussed with physical significance. The obtained results indicate that both radial and axial fields are the escalating functions of the Eyring–Powell fluid parameter. Moreover, the heat transfer rate enhances with the improving variable thermal conductivity parameter.
Dimethylation of histone H3 lysine 36 (H3K36me2) as a potential biomarker for glioma diagnosis, grading, and prognosis
Authors: Cong Huayue , Guo Xiaoqiang , Fan Bo , Liu Yingzi , Dong Changzheng , Sui Aixia 
Published: March 2023

Abstract
Abnormal histone methylation plays a key role in glioma development but the clinical value of specific alterations is still unclear. Here, the potential significance of histone H3 lysine 36 dimethylation (H3K36me2) was investigated as a biomarker for glioma. Seventy-three glioma patients were included in the study and the level of H3K36me2 in the tumor tissues was determined by immunohistochemistry. The χ2 test was used to explore the influence of clinical and pathological characteristics on H3K36me2 levels. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS). COX regression was used to explore the relationship between H3K36me2 levels and glioma prognosis. The results indicated that the H3K36me2 level increases with glioma grade. The proportion of high H3K36me2 levels was lower in glioma patients under the age of 52 years. H3K36me2 levels were negatively correlated with IDH1 mutation and MGMT promoter methylation, and positively correlated with p53 expression. Thus, high H3K36me2 levels positively correlated with poor prognosis of gliomas. In conclusion, H3K36me2 may be considered as a potential biomarker for glioma diagnosis, grading, and prognosis, but the overall clinical value of H3K36me2 determination deserves further investigation. These results may have important implications for accurate diagnosis and future precision treatment of gliomas.
Why we stopped listening to the other side: how partisan cues in news coverage undermine the deliberative foundations of democracy
Authors: Arendt Florian , Northup Temple , Forrai Michaela , Scheufele Dietram 
Published: March 2023

AbstractRecent theorizing on deliberative democracy has put political listening at the core of meaningful democratic deliberation. In the present experiment (N = 827), we investigated whether news media can improve diverse political listening in the United States via a reduction in party cue salience. Although Republican (Democratic) participants showed a strong preference for listening to speeches given by Republican (Democratic) politicians when party cues were highly salient, this bias in selective political listening was reduced or even absent when news items provided no or only low-salience cues. Conditional process analysis indicated that (automatically activated) implicit and (overtly expressed) explicit party attitudes mediated this effect. There are important implications: Current journalism practices tend to exacerbate tribal us-vs-them thinking by emphasizing partisan cues, nudging citizens toward not listening to political ideas from the other political camp. A more helpful news-choice architecture tones down partisan language, nudging citizens toward more diverse political listening.
A multimodal turn in Digital Humanities. Using contrastive machine learning models to explore, enrich, and analyze digital visual historical collections
Authors: Smits Thomas , Wevers Melvin 
Published: March 2023

Abstract
Until recently, most research in the Digital Humanities (DH) was monomodal, meaning that the object of analysis was either textual or visual. Seeking to integrate multimodality theory into the DH, this article demonstrates that recently developed multimodal deep learning models, such as Contrastive Language Image Pre-training (CLIP), offer new possibilities to explore and analyze image–text combinations at scale. These models, which are trained on image and text pairs, can be applied to a wide range of text-to-image, image-to-image, and image-to-text prediction tasks. Moreover, multimodal models show high accuracy in zero-shot classification, i.e. predicting unseen categories across heterogeneous datasets. Based on three exploratory case studies, we argue that this zero-shot capability opens up the way for a multimodal turn in DH research. Moreover, multimodal models allow scholars to move past the artificial separation of text and images that was dominant in the field and analyze multimodal meaning at scale. However, we also need to be aware of the specific (historical) bias of multimodal deep learning that stems from biases in the training data used to train these models.
The need for obscured supermassive black hole growth to explain quasar proximity zones in the epoch of reionization
Authors: Satyavolu Sindhu , Kulkarni Girish , Keating Laura C , Haehnelt Martin G 
Published: March 2023

ABSTRACTProximity zones of high-redshift quasars are unique probes of supermassive black hole formation, but simultaneously explaining proximity zone sizes and black hole masses has proved to be challenging. We study the robustness of some of the assumptions that are usually made to infer quasar lifetimes from proximity zone sizes. We show that small proximity zones can be readily explained by quasars that vary in brightness with a short duty cycle of fduty ∼ 0.1 and short bright periods of ton ∼ 104 yr, even for long lifetimes. We further show that reconciling this with black hole mass estimates requires the black hole to continue to grow and accrete during its obscured phase. The consequent obscured fractions of ≳ 0.7 or higher are consistent with low-redshift measurements and models of black hole accretion. Such short duty cycles and long obscured phases are also consistent with observations of large proximity zones, thus providing a simple, unified model for proximity zones of all sizes. The large dynamic range of our simulation, and its calibration to the Lyman-α forest, allows us to investigate the influence of the large-scale topology of reionization and the quasar’s host halo mass on proximity zones. We find that incomplete reionization can impede the growth of proximity zones and make them smaller up to 30 per cent, but the quasar host halo mass only affects proximity zones weakly and indirectly. Our work suggests that high-redshift proximity zones can be an effective tool to study quasar variability and black hole growth.
Epigenetic CpG duplex marks probed by an evolved DNA reader via a well-tempered conformational plasticity
Authors: Singh Himanshu , Das Chandan K , Buchmuller Benjamin C , Schäfer Lars V , Summerer Daniel , Linser Rasmus 
Published: March 2023

Abstract
5-methylcytosine (mC) and its TET-oxidized derivatives exist in CpG dyads of mammalian DNA and regulate cell fate, but how their individual combinations in the two strands of a CpG act as distinct regulatory signals is poorly understood. Readers that selectively recognize such novel ‘CpG duplex marks’ could be versatile tools for studying their biological functions, but their design represents an unprecedented selectivity challenge. By mutational studies, NMR relaxation, and MD simulations, we here show that the selectivity of the first designer reader for an oxidized CpG duplex mark hinges on precisely tempered conformational plasticity of the scaffold adopted during directed evolution. Our observations reveal the critical aspect of defined motional features in this novel reader for affinity and specificity in the DNA/protein interaction, providing unexpected prospects for further design progress in this novel area of DNA recognition.
Generating minimum set of gRNA to cover multiple targets in multiple genomes with MINORg
Authors: Lee Rachelle R Q , Cher Wei Yuan , Wang Jinge , Chen Yujie , Chae Eunyoung 
Published: March 2023

Abstract
MINORg is an offline gRNA design tool that generates the smallest possible combination of gRNA capable of covering all desired targets in multiple non-reference genomes. As interest in pangenomic research grows, so does the workload required for large screens in multiple individuals. MINORg aims to lessen this workload by capitalising on sequence homology to favour multi-target gRNA while simultaneously screening multiple genetic backgrounds in order to generate reusable gRNA panels. We demonstrated the practical application of MINORg by knocking out 11 homologous genes tandemly arrayed in a multi-gene cluster in two Arabidopsis thaliana lineages using three gRNA output by MINORg. We also described a new PCR-free modular cloning system for multiplexing gRNA, and used it to knockout three tandemly arrayed genes in another multi-gene cluster with gRNA designed by MINORg. Source code is freely available at https://github.com/rlrq/MINORg.
Widely spaced and divergent inverted repeats become a potent source of chromosomal rearrangements in long single-stranded DNA regions
Authors: Ait Saada Anissia , Guo Wenying , Costa Alex B , Yang Jiaxin , Wang Jianrong , Lobachev Kirill S 
Published: March 2023

Abstract
DNA inverted repeats (IRs) are widespread across many eukaryotic genomes. Their ability to form stable hairpin/cruciform secondary structures is causative in triggering chromosome instability leading to several human diseases. Distance and sequence divergence between IRs are inversely correlated with their ability to induce gross chromosomal rearrangements (GCRs) because of a lesser probability of secondary structure formation and chromosomal breakage. In this study, we demonstrate that structural parameters that normally constrain the instability of IRs are overcome when the repeats interact in single-stranded DNA (ssDNA). We established a system in budding yeast whereby &gt;73 kb of ssDNA can be formed in cdc13-707fs mutants. We found that in ssDNA, 12 bp or 30 kb spaced Alu-IRs show similarly high levels of GCRs, while heterology only beyond 25% suppresses IR-induced instability. Mechanistically, rearrangements arise after cis-interaction of IRs leading to a DNA fold-back and the formation of a dicentric chromosome, which requires Rad52/Rad59 for IR annealing as well as Rad1-Rad10, Slx4, Msh2/Msh3 and Saw1 proteins for nonhomologous tail removal. Importantly, using structural characteristics rendering IRs permissive to DNA fold-back in yeast, we found that ssDNA regions mapped in cancer genomes contain a substantial number of potentially interacting and unstable IRs.
Synergistic binding of actinomycin D and echinomycin to DNA mismatch sites and their combined anti-tumour effects
Authors: Satange Roshan , Chang Chih-Chun , Li Long-Yuan , Lin Sheng-Hao , Neidle Stephen , Hou Ming-Hon 
Published: March 2023

Abstract
Combination cancer chemotherapy is one of the most useful treatment methods to achieve a synergistic effect and reduce the toxicity of dosing with a single drug. Here, we use a combination of two well-established anticancer DNA intercalators, actinomycin D (ActD) and echinomycin (Echi), to screen their binding capabilities with DNA duplexes containing different mismatches embedded within Watson-Crick base-pairs. We have found that combining ActD and Echi preferentially stabilised thymine-related T:T mismatches. The enhanced stability of the DNA duplex–drug complexes is mainly due to the cooperative binding of the two drugs to the mismatch duplex, with many stacking interactions between the two different drug molecules. Since the repair of thymine-related mismatches is less efficient in mismatch repair (MMR)-deficient cancer cells, we have also demonstrated that the combination of ActD and Echi exhibits enhanced synergistic effects against MMR-deficient HCT116 cells and synergy is maintained in a MMR-related MLH1 gene knockdown in SW620 cells. We further accessed the clinical potential of the two-drug combination approach with a xenograft mouse model of a colorectal MMR-deficient cancer, which has resulted in a significant synergistic anti-tumour effect. The current study provides a novel approach for the development of combination chemotherapy for the treatment of cancers related to DNA-mismatches.
Nerve pathology is prevented by linker proteins in mouse models forLAMA2-related muscular dystrophy
Authors: Reinhard Judith R , Porrello Emanuela , Lin Shuo , Pelczar Pawel , Previtali Stefano C , Rüegg Markus A 
Published: March 2023

AbstractLAMA2-related muscular dystrophy (LAMA2 MD or MDC1A) is a devastating congenital muscular dystrophy that is caused by mutations in the LAMA2 gene encoding laminin-α2, the long chain of several heterotrimeric laminins. Laminins are essential components of the extracellular matrix that interface with underlying cells. The pathology of LAMA2 MD patients is dominated by an early-onset, severe muscular dystrophy that ultimately leads to death by respiratory insufficiency. However, pathology in nonmuscle tissues has been described. Prior work in the dyW/dyW mouse model for LAMA2 MD has shown that two linker proteins, mini-agrin and αLNNd, when expressed in skeletal muscle fibers, greatly increase survival from a few months up to more than 2 years. However, the restoration of skeletal muscle function accentuates the pathology in nonmuscle tissue in dyW/dyW mice, first and foremost in the peripheral nerve resulting in paralysis of the hind limbs. We now show that the expression of the two linker proteins in all tissues ameliorates the muscular dystrophy and prevents the appearance of the hind limb paralysis. Importantly, the same ameliorating effect of the linker proteins was seen in dy3K/dy3K mice, which represent the most severe mouse model of LAMA2 MD. In summary, these data show that the two linker proteins can compensate the loss of laminin-α2 in muscle and peripheral nerve, which are the two organs most affected in LAMA2 MD. These results are of key importance for designing appropriate expression constructs for mini-agrin and αLNNd to develop a gene therapy for LAMA2 MD patients.
Feasibility and preliminary efficacy of app-based audio tools to improve sleep health in working adults experiencing poor sleep: a multi-arm randomized pilot trial
Authors: Economides Marcos , Male Rhian , Bolton Heather , Cavanagh Kate 
Published: March 2023

Abstract

Study Objectives
Many adults without a diagnosed sleep disorder report poor sleep. Recently, there has been a dramatic increase in the use of app-based audio tools to aid sleep by the general public, yet there is a paucity of evidence on whether such tools are efficacious. This study evaluated the feasibility and preliminary efficacy of two categories of audio tools, comprising music and narrated stories, featured on the Unmind app.

Methods
We conducted an online, parallel, multi-arm, external pilot randomized controlled trial, with two intervention arms and a waitlist (WL) control group. Participants were working adults who were screened for poor sleep. Feasibility was assessed via objective and self-report measures. Preliminary efficacy was evaluated via self-report measures of sleep disturbance, work productivity, and other mental health outcomes, captured at baseline (t0) and following a 4-week intervention period (t1), and analyzed using mixed effects models with intention-to-treat principles.

Results
Three hundred participants were randomized, and 92% were retained at t1. 90.5% of participants completed at least one intervention session. 82.1% reported being “satisfied” or “very satisfied” with their intervention, and 84.3% rated their intervention as “good” or “excellent.” The between-group Hedges’ g effect size for sleep disturbance was 0.92 [0.63–1.22] and 1.09 [0.80–1.39] for the two interventions compared to the WL group.

Conclusions
Both interventions are feasible and acceptable. Preliminary efficacy findings suggest that audio tools designed to aid sleep could have widespread financial and public health implications, and should be investigated in a definitive trial.

Clinical Trial
International Standard Randomized Controlled Trial Number (ISRCTN), 12614821, http://www.isrctn.com/ISRCTN12614821.