bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the phenomenological and intrinsic blazar sequence using a simple scaling model
Authors: Wan Zhu-Jian , Xue Rui , Wang Ze-Rui , Xiao Hu-Bing , Fan Jun-Hui 
Published: February 2024

ABSTRACT
The blazar sequence, including negative correlations between radiative luminosity Lrad and synchrotron peak frequency ν, and between Compton dominance Y and ν, is widely adopted as a phenomenological description of spectral energy distributions (SEDs) of blazars, although its underlying cause is hotly debated. In particular, these correlations turn positive after correcting Doppler boosting effect. In this work, we revisit the phenomenological and intrinsic blazar sequence with three samples, which are historical sample (SEDs are built with historical data), quasi-simultaneous sample (SEDs are built with quasi-simultaneous data) and Doppler factor corrected sample (a sample with available Doppler factors), selected from literature. We find that phenomenological blazar sequence holds in historical sample, but does not exist in quasi-simultaneous sample, and intrinsic correlation between Lrad and ν becomes positive in Doppler factor corrected sample. We also analyse if the blazar sequence still exists in subclasses of blazars, i.e. flat-spectrum radio quasars and BL Lacertae objects, with different values of Y. To interpret these correlations, we apply a simple scaling model, in which physical parameters of the dissipation region are connected to the location of the dissipation region. We find that the model generated results are highly sensitive to the chosen ranges and distributions of physical parameters. Therefore, we suggest that even though the simple scaling model can reproduce the blazar sequence under specific conditions that have been fine-tuned, such results may not have universal applicability. Further consideration of a more realistic emission model is expected.
Shining light on the hosts of the nano-Hertz gravitational wave sources: a theoretical perspective
Authors: Saeedzadeh Vida , Mukherjee Suvodip , Babul Arif , Tremmel Michael , Quinn Thomas R 
Published: February 2024

ABSTRACT
The formation of supermassive black holes (SMBHs) in the Universe and its role in the properties of the galaxies is one of the open questions in astrophysics and cosmology. Though, traditionally, electromagnetic waves have been instrumental in direct measurements of SMBHs, significantly influencing our comprehension of galaxy formation, gravitational waves (GW) bring an independent avenue to detect numerous binary SMBHs in the observable Universe in the nano-Hertz range using the pulsar timing array observation. This brings a new way to understand the connection between the formation of binary SMBHs and galaxy formation if we can connect theoretical models with multimessenger observations namely GW data and galaxy surveys. Along these lines, we present here the first paper on this series based on romulus25 cosmological simulation on the properties of the host galaxies of SMBHs and propose on how this can be used to connect with observations of nano-Hertz GW signal and galaxy surveys. We show that the most dominant contribution to the background will arise from sources with high chirp masses which are likely to reside in low-redshift early-type galaxies with high stellar mass, largely old stellar population, and low star formation rate, and that reside at centres of galaxy groups and manifest evidence of recent mergers. The masses of the sources show a correlation with the halo mass and stellar mass of the host galaxies. This theoretical study will help in understanding the host properties of the GW sources and can help in establishing a connection with observations.
A Critical Appraisal of DNA Transfer from Plants to Parasitic Cyst Nematodes
Authors: Ko Itsuhiro , Kranse Olaf Prosper , Senatori Beatrice , Eves-van den Akker Sebastian 
Published: February 2024

Abstract
Plant-parasitic nematodes are one of the most economically important pests of crops. It is widely accepted that horizontal gene transfer—the natural acquisition of foreign genes in parasitic nematodes—contributes to parasitism. However, an apparent paradox has emerged from horizontal gene transfer analyses: On the one hand, distantly related organisms with very dissimilar genetic structures (i.e. bacteria), and only transient interactions with nematodes as far as we know, dominate the list of putative donors, while on the other hand, considerably more closely related organisms (i.e. the host plant), with similar genetic structure (i.e. introns) and documented long-term associations with nematodes, are rare among the list of putative donors. Given that these nematodes ingest cytoplasm from a living plant cell for several weeks, there seems to be a conspicuous absence of plant-derived cases. Here, we used comparative genomic approaches to evaluate possible plant-derived horizontal gene transfer events in plant parasitic nematodes. Our evidence supports a cautionary message for plant-derived horizontal gene transfer cases in the sugar beet cyst nematode, Heterodera schachtii. We propose a 4-step model for horizontal gene transfer from plant to parasite in order to evaluate why the absence of plant-derived horizontal gene transfer cases is observed. We find that the plant genome is mobilized by the nematode during infection, but that uptake of the said “mobilome” is the first major barrier to horizontal gene transfer from host to nematode. These results provide new insight into our understanding of the prevalence/role of nucleic acid exchange in the arms race between plants and plant parasites.
Secondary Contact, Introgressive Hybridization, and Genome Stabilization in Sticklebacks
Authors: Feng Xueyun , Merilä Juha , Löytynoja Ari 
Published: February 2024

AbstractAdvances in genomic studies have revealed that hybridization in nature is pervasive and raised questions about the dynamics of different genetic and evolutionary factors following the initial hybridization event. While recent research has proposed that the genomic outcomes of hybridization might be predictable to some extent, many uncertainties remain. With comprehensive whole-genome sequence data, we investigated the genetic introgression between 2 divergent lineages of 9-spined sticklebacks (Pungitius pungitius) in the Baltic Sea. We found that the intensity and direction of selection on the introgressed variation has varied across different genomic elements: while functionally important regions displayed reduced rates of introgression, promoter regions showed enrichment. Despite the general trend of negative selection, we identified specific genomic regions that were enriched for introgressed variants, and within these regions, we detected footprints of selection, indicating adaptive introgression. Geographically, we found the selection against the functional changes to be strongest in the vicinity of the secondary contact zone and weaken as a function of distance from the initial contact. Altogether, the results suggest that the stabilization of introgressed variation in the genomes is a complex, multistage process involving both negative and positive selection. In spite of the predominance of negative selection against introgressed variants, we also found evidence for adaptive introgression variants likely associated with adaptation to Baltic Sea environmental conditions.
The Effects of De Novo Mutation on Gene Expression and the Consequences for Fitness in Chlamydomonas reinhardtii
Authors: Balogun Eniolaye J , Ness Rob W 
Published: February 2024

Abstract
Mutation is the ultimate source of genetic variation, the bedrock of evolution. Yet, predicting the consequences of new mutations remains a challenge in biology. Gene expression provides a potential link between a genotype and its phenotype. But the variation in gene expression created by de novo mutation and the fitness consequences of mutational changes to expression remain relatively unexplored. Here, we investigate the effects of &gt;2,600 de novo mutations on gene expression across the transcriptome of 28 mutation accumulation lines derived from 2 independent wild-type genotypes of the green algae Chlamydomonas reinhardtii. We observed that the amount of genetic variance in gene expression created by mutation (Vm) was similar to the variance that mutation generates in typical polygenic phenotypic traits and approximately 15-fold the variance seen in the limited species where Vm in gene expression has been estimated. Despite the clear effect of mutation on expression, we did not observe a simple additive effect of mutation on expression change, with no linear correlation between the total expression change and mutation count of individual MA lines. We therefore inferred the distribution of expression effects of new mutations to connect the number of mutations to the number of differentially expressed genes (DEGs). Our inferred DEE is highly L-shaped with 95% of mutations causing 0-1 DEG while the remaining 5% are spread over a long tail of large effect mutations that cause multiple genes to change expression. The distribution is consistent with many cis-acting mutation targets that affect the expression of only 1 gene and a large target of trans-acting targets that have the potential to affect tens or hundreds of genes. Further evidence for cis-acting mutations can be seen in the overabundance of mutations in or near differentially expressed genes. Supporting evidence for trans-acting mutations comes from a 15:1 ratio of DEGs to mutations and the clusters of DEGs in the co-expression network, indicative of shared regulatory architecture. Lastly, we show that there is a negative correlation with the extent of expression divergence from the ancestor and fitness, providing direct evidence of the deleterious effects of perturbing gene expression.
Human pangenome analysis of sequences missing from the reference genome reveals their widespread evolutionary, phenotypic, and functional roles
Authors: Wu Zhikun , Li Tong , Jiang Zehang , Zheng Jingjing , Gu Yizhou , Liu Yizhi , Liu Yun , Xie Zhi 
Published: February 2024

Abstract
Nonreference sequences (NRSs) are DNA sequences present in global populations but absent in the current human reference genome. However, the extent and functional significance of NRSs in the human genomes and populations remains unclear. Here, we de novo assembled 539 genomes from five genetically divergent human populations using long-read sequencing technology, resulting in the identification of 5.1 million NRSs. These were merged into 45284 unique NRSs, with 29.7% being novel discoveries. Among these NRSs, 38.7% were common across the five populations, and 35.6% were population specific. The use of a graph-based pangenome approach allowed for the detection of 565 transcript expression quantitative trait loci on NRSs, with 426 of these being novel findings. Moreover, 26 NRS candidates displayed evidence of adaptive selection within human populations. Genes situated in close proximity to or intersecting with these candidates may be associated with metabolism and type 2 diabetes. Genome-wide association studies revealed 14 NRSs to be significantly associated with eight phenotypes. Additionally, 154 NRSs were found to be in strong linkage disequilibrium with 258 phenotype-associated SNPs in the GWAS catalogue. Our work expands the understanding of human NRSs and provides novel insights into their functions, facilitating evolutionary and biomedical researches.
Zebrafish Mbd5 binds to RNA m5C and regulates histone deubiquitylation and gene expression in development metabolism and behavior
Authors: Guo Jianhua , Zou Zhongyu , Dou Xiaoyang , Zhao Xiang , Wang Yimin , Wei Liqiang , Pi Yan , Wang Yi , He Chuan , Guo Su 
Published: February 2024

Abstract
Complex biological processes are regulated by both genetic and epigenetic programs. One class of epigenetic modifications is methylation. Evolutionarily conserved methyl-CpG-binding domain (MBD)-containing proteins are known as readers of DNA methylation. MBD5 is linked to multiple human diseases but its mechanism of action remains unclear. Here we report that the zebrafish Mbd5 does not bind to methylated DNA; but rather, it directly binds to 5-methylcytosine (m5C)-modified mRNAs and regulates embryonic development, erythrocyte differentiation, iron metabolism, and behavior. We further show that Mbd5 facilitates removal of the monoubiquitin mark at histone H2A-K119 through an interaction with the Polycomb repressive deubiquitinase (PR-DUB) complex in vivo. The direct target genes of Mbd5 are enriched with both RNA m5C and H2A-K119 ubiquitylation signals. Together, we propose that zebrafish MBD5 is an RNA m5C reader that potentially links RNA methylation to histone modification and in turn transcription regulation in vivo.
A Fur family protein BosR is a novel RNA-binding protein that controls rpoS RNA stability in the Lyme disease pathogen
Authors: Raghunandanan Sajith , Priya Raj , Alanazi Fuad , Lybecker Meghan C , Schlax Paula Jean , Yang X Frank 
Published: February 2024

Abstract
The σ54-σS sigma factor cascade plays a central role in regulating differential gene expression during the enzootic cycle of Borreliella burgdorferi, the Lyme disease pathogen. In this pathway, the primary transcription of rpoS (which encodes σS) is under the control of σ54 which is activated by a bacterial enhancer-binding protein (EBP), Rrp2. The σ54-dependent activation in B. burgdorferi has long been thought to be unique, requiring an additional factor, BosR, a homologue of classical Fur/PerR repressor/activator. However, how BosR is involved in this σ54-dependent activation remains unclear and perplexing. In this study, we demonstrate that BosR does not function as a regulator for rpoS transcriptional activation. Instead, it functions as a novel RNA-binding protein that governs the turnover rate of rpoS mRNA. We further show that BosR directly binds to the 5′ untranslated region (UTR) of rpoS mRNA, and the binding region overlaps with a region required for rpoS mRNA degradation. Mutations within this 5′UTR region result in BosR-independent RpoS production. Collectively, these results uncover a novel role of Fur/PerR family regulators as RNA-binding proteins and redefine the paradigm of the σ54–σS pathway in B. burgdorferi.
Nuclear RNA-related processes modulate the assembly of cytoplasmic RNA granules
Authors: Angel Mor , Fleshler Eden , Atrash Mohammad Khaled , Kinor Noa , Benichou Jennifer I C , Shav-Tal Yaron 
Published: February 2024

Abstract
Stress granules (SGs) are cytoplasmic assemblies formed under various stress conditions as a consequence of translation arrest. SGs contain RNA-binding proteins, ribosomal subunits and messenger RNAs (mRNAs). It is well known that mRNAs contribute to SG formation; however, the connection between SG assembly and nuclear processes that involve mRNAs is not well established. Here, we examine the effects of inhibiting mRNA transcription, splicing and export on the assembly of SGs and the related cytoplasmic P body (PB). We demonstrate that inhibition of mRNA transcription, splicing and export reduces the formation of canonical SGs in a eukaryotic initiation factor 2α phosphorylation-independent manner, and alters PB size and quantity. We find that the splicing inhibitor madrasin promotes the assembly of stress-like granules. We show that the addition of synthetic mRNAs directly to the cytoplasm is sufficient for SG assembly, and that the assembly of these SGs requires the activation of stress-associated protein synthesis pathways. Moreover, we show that adding an excess of mRNA to cells that do not have active splicing, and therefore have low levels of cytoplasmic mRNAs, promotes SG formation under stress conditions. These findings emphasize the importance of the cytoplasmic abundance of newly transcribed mRNAs in the assembly of SGs.
Preclinical evaluation of the third-generation, bi-steric mechanistic target of rapamycin complex 1-selective inhibitor RMC-6272 in NF2-deficient models
Authors: Bhattacharyya Srirupa , Oblinger Janet L , Beauchamp Roberta L , Kosa Lili , Robert Francis , Plotkin Scott R , Chang Long-Sheng , Ramesh Vijaya 
Published: February 2024

Abstract

Background
NF2-associated meningiomas are progressive, highly morbid, and nonresponsive to chemotherapies, highlighting the need for improved treatments. We have established aberrant activation of the mechanistic target of rapamycin (mTOR) signaling in NF2-deficient tumors, leading to clinical trials with first- and second-generation mTOR inhibitors. However, results have been mixed, showing stabilized tumor growth without shrinkage offset by adverse side effects. To address these limitations, here we explored the potential of third-generation, bi-steric mTOR complex 1 (mTORC1) inhibitors using the preclinical tool compound RMC-6272.

Methods
Employing human NF2-deficient meningioma lines, we compared mTOR inhibitors rapamycin (first-generation), INK128 (second-generation), and RMC-6272 (third-generation) using in vitro dose–response testing, cell-cycle analysis, and immunoblotting. Furthermore, the efficacy of RMC-6272 was assessed in NF2-null 3D-spheroid meningioma models, and its in vivo potential was evaluated in 2 orthotopic meningioma mouse models.

Results
Treatment of meningioma cells revealed that, unlike rapamycin, RMC-6272 demonstrated superior growth inhibitory effects, cell-cycle arrest, and complete inhibition of phosphorylated 4E-BP1 (mTORC1 readout). Moreover, RMC-6272 had a longer retention time than INK128 and inhibited the expression of several eIF4E-sensitive targets on the protein level. RMC-6272 treatment of NF2 spheroids showed significant shrinkage in size as well as reduced proliferation. Furthermore, in vivo studies in mice revealed effective blockage of meningioma growth by RMC-6272, compared with vehicle controls.

Conclusions
Our study in preclinical models of NF2 supports possible future clinical evaluation of third-generation, investigational mTORC1 inhibitors, such as RMC-5552, as a potential treatment strategy for NF2.
The Effectiveness of Text Support for Stopping Smoking in Pregnancy (MiQuit): Multi-Trial Pooled Analysis Investigating Effect Moderators and Mechanisms of Action
Authors: Emery Joanne , Leonardi-Bee Jo , Coleman Tim , McDaid Lisa , Naughton Felix 
Published: February 2024

Abstract

Introduction
Digital cessation support appeals to pregnant smokers. In two pooled RCTs, MiQuit, a pregnancy-specific tailored text messaging intervention, did not show effectiveness for validated prolonged abstinence. However, secondary outcomes and potential moderators and mediators have not been investigated. We aimed to determine, using pooled RCT data: (1) MiQuit effectiveness on a range of smoking outcomes; (2) whether baseline tobacco dependence or quit motivation moderate effectiveness; (3) whether hypothesized mechanisms of action (quitting determination, self-efficacy, baby harm beliefs, lapse prevention strategies) mediate effectiveness.

Methods
Pooled data analysis from two procedurally identical RCTs comparing MiQuit (N = 704) to usual care (N = 705). Participants were smokers, &lt;25 weeks pregnant, recruited from 40 English antenatal clinics. Outcomes included self-reported 7-day abstinence at 4 weeks post-baseline and late pregnancy, and prolonged abstinence. Late pregnancy outcomes were also biochemically validated. We used hierarchical regression and structural equation modeling.

Results
MiQuit increased self-reported, 7-day abstinence at 4 weeks (OR = 1.73 [95% CI 1.10–2.74]) and was borderline significant at late pregnancy (OR = 1.34 [0.99–1.82]) but not for prolonged or validated outcomes. Effectiveness was not moderated by baseline dependence (heaviness of smoking “low” vs. “moderate–high”) or motivation (planning to quit ≤30 days [high] vs. &gt;30 days [low]), but effects on self-reported outcomes were larger for the high motivation sub-group. MiQuit had a small effect on mean lapse prevention strategies (MiQuit 8.6 [SE 0.17], UC 8.1 [SE 0.17]; P = .030) but not other mechanisms.

Conclusions
MiQuit increased short-term but not prolonged or validated abstinence and may be most effective for those motivated to quit sooner.

Implications
Digital cessation support appeals to pregnant smokers. MiQuit, a tailored, theory-guided text messaging program for quitting smoking in pregnancy, has not shown effectiveness for validated prolonged abstinence in two previous RCTs but its impact on other smoking outcomes and potential mechanisms of action are unknown. When pooling trial data, MiQuit increased self-reported short-term abstinence, including making a quit attempt and abstinence at 4-week follow-up, but not late pregnancy, sustained, or validated abstinence. MiQuit appeared effective at late pregnancy for participants with high quitting motivation, but its mechanisms of action remain uncertain. Additional support components are likely required to enhance effectiveness.
Nutritional interventions in prison settings: a scoping review
Authors: Vetrani Claudia , Verde Ludovica , Ambretti Antinea , Muscogiuri Giovanna , Pagano Antonio Maria , Lucania Luciano , Colao Annamaria , Barrea Luigi 
Published: February 2024

Abstract

Background
Mounting evidence has shown that incarceration can affect the health and well-being of individuals and increase the risk of noncommunicable diseases (NCDs). Diet quality is known to be one of the main determinants of risk of NCDs, and dietary changes are the first approach used in primary care to reduce the incidence of NCDs.

Objective
This scoping review aimed to summarize the evidence for (1) the diet quality of inmates, and (2) the effect of nutritional intervention in prison systems. In addition, we aimed to describe limitations in the current literature and to suggest potential future research areas.

Method
A systematic search was performed in 2 databases (PubMed and Web of Science) using predefined search terms and covering the period May 2023 to June 2023. Additionally, reference lists from the retrieved studies were hand-searched to identify any additional relevant publications. The identified literature was screened based on defined search strategies, criteria, and research questions defined using the PICo (population or problem, interest, and context) framework. The review was conducted referring to the PRISMA-ScR and the PICo framework.

Results
A total of 19 studies out of 63 initially identified records were included in this review (11 cross-sectional evaluations and 9 intervention-based studies). In almost all studies, assessment of the diet quality of menus showed the menus to be nutritionally adequate, except for having a higher-than-recommended intake of total energy, saturated fatty acids, sodium, cholesterol, and sugar. In addition, some studies reported a lower-than-recommended intake of fiber, magnesium, potassium, vitamins D, E, and A, and omega-3 fatty acids. Nutritional interventions were mainly planned in the form of workshops, seminars, and written material to deliver information on healthy dietary choices. Although no significant changes in inmates’ dietary choices were observed in any of the studies, a high participation rate was detected.

Conclusion
Inmates might require additional prevention intervention to reduce their susceptibility to cardiometabolic diseases by virtue of their isolation from community facilities. Interventions should be tailored to the characteristics of prison settings and inmates to increase adherence to nutritional recommendations.