bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural variation in chalcone isomerase defines a major locus controlling radial stem growth variation amongPopulus nigrapopulations
Authors: Duruflé Harold , Déjardin Annabelle , Jorge Véronique , Pégard Marie , Pilate Gilles , Rogier Odile , Sanchez Leopoldo , Segura Vincent 
Published: October 2024

AbstractPoplar is a promising resource for wood production and the development of lignocel-lulosic biomass, but currently available varieties have not been optimized for these purposes. Therefore, it is critical to investigate the genetic variability and mechanisms underlying traits that affect biomass yield. Previous studies have shown that target traits in different poplar species are complex, with a small number of genetic factors having relatively low effects compared to medium to high heritability. In this study, a systems biology approach was implemented, combining genomic, transcriptomic, and phenotypic information from a large collection of individuals from natural populations of black poplar from Western Europe. Such an approach identified a QTL and a gene, coding for chalcone isomerase (CHI), as a candidate for controlling radial growth. Additionally, analysis of the structure and diversity of traits as well as CHI gene expression revealed a high allelic fixation index, linked to the geographical origin of the natural populations under study. These findings provide insights into how adaptive traits arise, are selected, and maintained in the populations. Overall, this study contributes to enhancing the use of poplar as a valuable resource for sustainable biomass production.
Temporal placement of RNA modifications under 5-fluorouracil treatment in human cell culture
Authors: Berg Maximilian , Li Chengkang , Kaiser Stefanie 
Published: October 2024

ABSTRACTRecent studies have explored the dynamic changes in RNA modification across various organisms, often in response to stressors like chemical agents or drugs. Among these, the anticancer drug 5-fluorouracil (5-FU) has been evaluated regarding its impact on RNA and DNA. Although different alterations in RNA modification have been associated with 5-FU, a mechanistic insight into the dynamic effects on RNA modification is missing. In this study, we provide a detailed insight into the dynamic modification changes for tRNA and rRNA of HEK293T cells exposed to 5-FU using Nucleic Acid Isotope Labeling coupled Mass Spectrometry (NAIL-MS). Consistent with existing literature, we observed a constant loss of m5U in newly transcribed tRNA during 5-FU exposure. In addition to m5U, we identified a loss of m5Um and an increase of Um within tRNALysUUU. While cells recover from a 24-hour 5-FU treatment, we found changed abundances of modifications like an increase of mcm5U and m5C and a decrease of m7G and m1A in total tRNA. Moreover, we demonstrate that 5-FU affects various rRNA subtypes, altering both their modification stoichiometry and abundance. Taken together, we use NAIL-MS to deconvolute RNA modification abundance changes caused by drug treatment and we uncover patterns of RNA modification adaptation.
The E3 ligase NEDD4L prevents colorectal cancer liver metastasis via degradation of PRMT5 to inhibit the AKT/mTOR signaling pathway
Authors: Dong Zhewen , She Xiaofei , Ma Junxian , Chen Qian , Gao Yaqun , Chen Ruiyan , Qin Huanlong , Gao Hua 
Published: October 2024

AbstractColorectal cancer is the second most common cause of cancer mortality worldwide, and liver metastasis is the major cause of death in patients with colorectal cancer. Dysfunctional E3 ligase activity has recently been shown to be associated with colorectal cancer. However, the key E3 ligase affecting colorectal cancer liver metastasis remains unknown. Therefore, we used an shRNA library targeting 156 E3 ubiquitin ligases to perform anin vivoloss-of-function screen of a human colorectal cancer cell line in a mouse model of colorectal cancer liver metastasis. The screen revealed that NEDD4L knockdown promoted colorectal cancer liver metastasis. Moreover, overexpression of NEDD4L prevented colorectal cancer liver metastasis. Mechanistic studies revealed that NEDD4L bound to the PPNAY motif in PRMT5 and ubiquitinated PRMT5 to promote its degradation. PRMT5 degradation attenuated the methylation of an arginine residue in AKT1 to inhibit the AKT/mTOR signaling pathway, consequently decreasing colorectal cancer cell proliferation. We are the first to show that PRMT5 is a substrate protein of the E3 ligase NEDD4L and reveals not only the metastasis-inhibiting function of NEDD4L but also a novel mechanism by which NEDD4L suppresses colorectal cancer liver metastasis. These findings may provide a new preventive strategy for liver metastasis.
Hydroxy polyethylene glycol: a solution to evade human pre-existing anti-PEG antibodies for efficient delivery
Authors: Ding Tianhao , Fu Jiaru , Yang Min , Zhang Zui , Ma Yinyu , Wu Ercan , Guo Zhiwei , Lin Shiqi , Wang Songli , Liu Xiaohua , Wang Bin , Li Guanghui , Zhan Changyou 
Published: October 2024

AbstractPolyethylene glycol (PEG) has been extensively utilized in food, cosmetics, and pharmaceutical fields, especially in the realm of nanomedicines, where it serves as a pivotal excipient for extending the nanoparticles circulation half-life. Contrary to its historical perception as non-immunogenic, pre-existing anti-PEG antibodies have been widely detected in human who even have never been exposed to PEGylated therapeutics, which considered to be associated with serious side effects of PEGylated nanomedicines including infusion reactions and other hypersensitive reactions. Herein, we elucidated the prevalence and distribution characteristics of pre-existing anti-PEG antibodies in 2074 human blood samples, and investigated its binding with PEG. Pre-existing anti-PEG antibodies were found to primarily recognize the PEG terminus, especially methoxy, which is the only PEG terminus contained in currently marketed PEGylated nanomedicines. While hydroxy PEG (OH-PEG) significantly evaded binding with pre-existing anti-PEG antibodies among most clinical samples. Noteworthily, substituting OH-PEG for MeO-PEG significantly mitigated complement activation of lipid nanoparticle (LNP) caused by pre-existing anti-PEG antibodies, thereby markedly enhancing stability and reducing mRNA leakage in human serum. Additionally, LNP modified with OH-PEG exhibited reduced immunogenicity, which was crucial for repeated drug administrations. The present work elucidated the crucial role of OH-PEG in evading human pre-existing anti-PEG antibodies, and discovered that the current pre-clinical studies inadequately simulated the biological effects of clinical pre-existing anti-PEG antibodies on such formulations through interspecies study, which had a profound impact on clinical translation of PEGylated nanomedicines.
The fourspine stickleback (Apeltes quadracus) has an XY sex chromosome system with polymorphic inversions on both X and Y chromosomes
Authors: Liu Zuyao , Herbert Amy L. , Chan Yingguang Frank , Kučka Marek , Kingsley David M. , Peichel Catherine L. 
Published: October 2024

AbstractTeleost fish are well-known for possessing a diversity of sex chromosomes and for undergoing frequent turnovers of these sex chromosomes. However, previous studies have mainly focused on variation between species, while comparatively little attention has been given to sex chromosome polymorphisms within species, which may capture early stages of sex chromosome changes. To better understand the evolution of sex chromosomes, we used the fourspine stickleback (Apeltes quadracus) as a model organism. Previously, it was believed that females of this species possessed a ZW heteromorphic sex chromosome system. However, genetic crosses and our whole-genome sequencing of wild populations revealed thatA. quadracushas an XY sex chromosome on chromosome 23. This chromosome has not previously been identified as a sex chromosome in other stickleback species, indicating a recent sex chromosome turnover. We also identified two genes -rxfp2aandzar1l- as novel candidate sex determination genes. Notably, we observed inversions on both the X and Y chromosomes in different populations, resulting in distinctive patterns of differentiation between the X and Y chromosomes across populations. We propose that the inversion on the X chromosome may have been favored by sexually antagonistic selection. The new sex chromosome and intraspecies inversion polymorphisms observed inA. quadracusprovide an excellent system for studying the evolution of sex chromosomes and their turnovers.Author SummaryAs compared to mammals and birds, teleost fish exhibit a very high level of diversity in their sex chromosomes, even among closely related species. Thus far, little attention has been paid to variation within species, although it offers a valuable opportunity to advance our understanding of the mechanisms underlying the formation and turnover of sex chromosomes. Through a quantitative trait locus (QTL) cross and sequencing diverse populations, we determined that instead of the previously reported ZW system,A. quadracushas an XY sex determination system on chromosome 23. Within the sex determining region, we identifiedrxfp2aandzar1las putative sex determining genes. Notably, we also observed polymorphic inversions present on both the X and Y chromosomes that differ among populations. Based on our findings, we hypothesize that the X-linked inversions are favored by selection that differs between males and females. These observations represent a rare situation in which sex chromosomes are still polymorphic for sex-linked inversions, which offers important insights into the early stages of sex chromosome evolution.
Effect of p-benzoquinone, a cigarette smoke-derived component, on the architecture and function of human RBC
Authors: Yadav Neha , Mondal Santosh Kumar , Mandal Amit Kumar 
Published: October 2024

Abstractp-benzoquinone (pBQ), a cigarette smoke-derived component, stands as one of the lethal oxidants of cigarette smoke. Health hazards caused by cigarette smoking are a profound global health concern. It has been reported to contribute significantly to several health disorders, such as lung cancer, chronic obstructive pulmonary disease (COPD), cardiovascular diseases, etc. These adverse health effects might be attributed to the complex mixture of approximately 4,000 chemicals present in cigarette smoke, such as nicotine, tar, nitric oxide, and p-benzosemiquinone (pBSQ). pBSQ, ranging from 100-200 µg per cigarette, gets oxidized to pBQ in the lungs of smokers and subsequently enters into the bloodstream. In the present study, we investigated the detrimental effect of pBQ on the architecture of human RBCs. Previously, we showed that the covalent modification of human hemoglobin with pBQ results in an alteration in its structure and function. In addition, we explored the potential neutralizing role of N-acetyl cysteine (NAC) in the reactivity of pBQ. Our results demonstrated that pBQ exposure to human red blood cells (RBCs),ex vivo, significantly decreases the reduced glutathione (GSH) content of RBCs, leading to the elevation of reactive oxygen species (ROS) and consequently causing oxidative damage to cellular components. pBQ exposure resulted in increased RBC sedimentation, altered membrane fluidity, enhanced lipid peroxidation, and significant morphological changes, such as bulging and distortion on the surface of RBCs, which eventually compromise membrane integrity. In addition, the coexistence of NAC with pBQ was found to be effective in neutralizing pBQ, thereby restoring GSH levels and RBC membrane architecture. These findings highlight the potential of NAC in mitigating the harmful effects of cigarette smoke on RBCs.Graphical abstract
Kernel Filter-Based Adaptive Controllers For Cybergenetics Applications
Authors: Smart Benjamin , Marucci Lucia , Renson Ludovic 
Published: October 2024

AbstractCybergenetics is an advancing field seeking to implement control theory within biological systems. When applying feedback control for the regulation of gene expression or cell proliferation, model-based control strategies can be applied; in this context, online adaptive mathematical models can be used to keep models in tune with the current behaviour of the biological system. Controllers are often constrained by their sampling rate, which is usually relatively low when using microfluidics/microscopy platforms. Current adaptive filters can lead to an inaccurate predictive model when operating with a low sampling rate, leading to sub-optimal control. Here, we propose a kernel filter that can adapt model parameters online to produce a more accurate predictive model that can be included within an adaptive model predictive control scheme. The use of the kernel filter is demonstrated inin silicoexperiments, where we control a synthetic gene network oscillator and a P53 oscillator. Results show that the kernel filter outperforms a particle filter when used for parameter estimation in both the predictive model accuracy and when included within an adaptive model-based controller.
Systemic effects of oral tolerance improve the healing of several and concomitant wounds in different body parts
Authors: Nobrega Isabela Beatriz Cabacinha , Souza Andrade Angélica Vitória , Nyetem Bikat Thomson Junior , Quintão Gustavo Motta , Azevedo Junior Geraldo Magela , Valência Karen Franco , Costa Raquel Alves , Carvalho Claudia Rocha 
Published: October 2024

AbstractThroughout our lives, we are continually subjected to different situations that can result in several and concomitant wounds to different parts of our body. The healing of these wounds is essential to maintaining health. Inflammation is an important step in wound healing, but in cases of intense or prolonged inflammation, pathological scarring or non-closure of the wound may occur. Assuming that leukocytes participate in wound healing and that it is possible to intervene systemically with inflammation, we investigated a way to promote better repair of multiple wounds that may occur at the same time. Oral tolerance is an immunological phenomenon that result from protein intake and that have systemic effects on inflammation. Previous works have shown that parenteral injection of tolerated proteins reduces the inflammatory infiltrate and improves skin wound healing. Herein we tested whether the injection of tolerated proteins improves the healing of several wounds in different body parts, such as on the skin of the back and in the external ear (the auricle). To induce oral tolerance to ovalbumin (OVA), eight weeks old C57BL/6 mice drank egg white diluted 1:5 in water for 3 consecutive days. Control mice drank water. Seven days after oral treatment, mice were submitted to excisional injuries in the skin of the back (6 mm) and in the ears (4 mm). Minutes before the injuries, the mice received an intraperitoneal injection of OVA + Al(OH)3. Seven and 40 days after injuries, tissue samples were collected and processed for histological analysis of the wounds. The results show that the injection of OVA in animals that drank OVA reduced the inflammatory infiltrate in all lesions. Besides, injection of OVA in animals that drank OVA promoted better organization of the extracellular matrix, with thicker and intertwined collagen fibers in the neodermis, resulting in smaller scars in the skin. Furthermore, the healing area of the ears of OVA-tolerant animals showed chondrocyte aggregates and less obvious fibrous scar tissue compared with control animals. In conclusion, systemic effects of oral tolerance positively influenced the healing of several lesions in different body parts.
Abundant genetic variation is retained in many laboratory schistosome populations
Authors: Jutzeler Kathrin S. , Platt Roy N. , Diaz Robbie , Morales Madison , Clec’h Winka LE , Chevalier Frédéric D. , Anderson Timothy J.C. 
Published: October 2024

ABSTRACTSchistosomes are obligately sexual blood flukes that can be maintained in the laboratory using freshwater snails as intermediate and rodents as definitive hosts. The genetic composition of laboratory schistosome populations is poorly understood: whether genetic variation has been purged due to serial inbreeding or retained is unclear. We sequenced 19 – 24 parasites from each of five laboratorySchistosoma mansonipopulations and compared their genomes with published exome data from fourS. mansonifield populations. We found abundant genomic variation (0.897 – 1.22 million variants) within laboratory populations: these retained on average 49% (π = 3.27e-04 – 8.94e-04) of the nucleotide diversity observed in the four field parasite populations (π = 1.08e-03 – 2.2e-03). However, the pattern of variation was very different in laboratory and field populations. Tajima’s D was positive in all laboratory populations except SmBRE, indicative of recent population bottlenecks, but negative in all field populations. Current effective population size estimates of laboratory populations were lower (2 – 258) compared to field populations (3,174 – infinity). The distance between markers at which linkage disequilibrium (LD) decayed to 0.5 was longer in laboratory populations (59 bp – 180 kb) compared to field populations (9 bp – 9.5 kb). SmBRE was the least variable; this parasite also shows low fitness across the lifecycle, consistent with inbreeding depression. The abundant genetic variation present in most laboratory schistosome populations has several important implications: (i) measurement of parasite phenotypes, such as drug resistance, using laboratory parasite populations will determine average values and underestimate trait variation; (ii) genome-wide association studies (GWAS) can be conducted in laboratory schistosome populations by measuring phenotypes and genotypes of individual worms; (iii) genetic drift may lead to divergence in schistosome populations maintained in different laboratories. We conclude that the abundant genetic variation retained within many laboratory schistosome populations can provide valuable, untapped opportunities for schistosome research.
A TEMPORAL MODEL OF TUMOR-IMMUNE DYNAMICS IN HIGH GRADE SEROUS OVARIAN CANCER
Authors: Egan Donagh , Glennon Kate , Treacy Ann , Fabre Aurelie , McCormack Janet , Hill Salisha , Morrison Ryan , Liebler Daniel , Kolch Walter , Brennan Donal 
Published: October 2024

ABSTRACTPatients with high-grade serous ovarian cancer (HGSOC) typically present with widespread metastasis, obscuring a temporal understanding of tumor-immune dynamics. We performed multi-site global proteomics and matched immunohistochemistry (IHC) of CD4+ and CD8+ tumor infiltrating lymphocytes (TILs) in patient samples. The protein expression profiles were ordered by pseudotime, recapitulating metastatic progression observed in the clinic, and providing a framework to explore tumor-immune dynamics from localized to metastatic disease. Metastatic progression correlated with immune cell infiltration and the recruitment of Tregs to counterbalance the effect of γδ and CD4+ T cells. Whilst later-stage metastases recruited Tregs via chemokines induced by SNX8, early-stage tumors relied more on antigen presentation. The exclusion of CD4+ TILs from the epithelium was correlated with metastatic progression, whereas CD8+ TILs were not, likely due to a predominance of exhausted CD8+ T cells. In early-stage tumors, keratin-expressing cancer cells recruited Tregs via MHC class II, resulting in an inflammatory phenotype characterized by limited IFNγ production and non-clonally expanded T cells. Additionally, IFI44L expression on macrophages caused immune exclusion by downregulating CD53 on T cells. Our findings reveal novel mechanisms of immune escape associated with localized disease and metastatic progression in HGSOC, highlighting potential targets to improve the efficacy of immunotherapy.
The dual trxG/PcG protein ULTRAPETALA1 modulates H3K27me3 and directly enhances POLYCOMB REPRESSIVE COMPLEX 2 activity for fine-tuned reproductive transitions
Authors: Geshkovski Vangeli , Engelhorn Julia , Izquierdo Jean-Baptiste , Laroussi Hamida , Thouly Caroline , Turchi Laura , Le Masson Marie , Thévenon Emmanuel , Petitalot Ambre , Simon Lauriane , Desset Sophie , Michl-Holzinger Philipp , Parrinello Hugues , Grasser Klaus D. , Probst Aline , Margueron Raphaël , Vachon Gilles , Kadlec Jan , Carles Cristel C. 
Published: October 2024

AbstractThe antagonistic POLYCOMB (PcG) REPRESSIVE COMPLEX 2 (PRC2) and trithorax (trxG) chromatin machineries play a major role in orchestrating gene expression during the development of multicellular eukaryotes. These complexes are well known for depositing and maintaining the repressive H3K27me3 and activating H3K4me3 marks, respectively. However, the mechanisms that govern the switch between these functions remains elusive, especially in plants, whose lifelong, flexible development relies heavily on this process. Here we demonstrate that the plant specific ULTRAPETALA1 (ULT1) protein, previously reported as a trxG factor that antagonizes the PRC2 enzymatic subunit CURLY LEAF (CLF), also exhibits a repressive function, increasing H3K27me3 levels at over a thousand genes. We discovered a physical interaction between ULT1 and PRC2 components, particularly the SWINGER (SWN) enzymatic subunit. We further show that ULT1 significantly enhances PRC2SWNenzymatic activityin vitro, corroborating our epigenomic and developmental genetic data that reveal different ULT1 activity depending on the catalytic subunit of the PRC2 complex. This study provides new insights into the relative activities of CLF and SWN and introduces a novel mechanistic framework for a chromatin switch mediated by a bivalent trxG/PcG factor.Key messageULTRAPETALA1 counteracts or promotes PRC2 activity at hundreds of developmental genes inArabidopsis thaliana, and activates the deposition of the repressive H3K27me3 chromatin mark via direct interaction with PRC2.This is the first instance of a bivalent trxG / PcG factor which functions as a cofactor of PRC2 HMTs.
Insufficient evidence for a severe bottleneck in humans during the Early to Middle Pleistocene transition
Authors: Cousins Trevor , Durvasula Arun 
Published: October 2024

AbstractA recently proposed model suggests a strong bottleneck in the panmictic ancestral population of modern humans during the Early to Middle Pleistocene transition. Here, we show this model provides a substantially worse fit to the data than a panmictic model without the bottleneck.
Vitamin E supplementation prevents ferroptosis in round spermatids of aged mice
Authors: Germeraad Jasper , Kikkawa Takako , Osumi Noriko 
Published: October 2024

AbstractGerm cell depletion in the aged testes has traditionally been attributed to removal by apoptosis. This study aimed to determine whether ferroptosis, an alternative form of cell death driven by iron-dependent lipid peroxidation, also contributes to germ cell loss in the lipid-rich environment of the testis. Here, we demonstrate that pre-meiotic cells are eliminated via apoptosis, whereas post-meiotic round spermatids (RSs) are mainly removed through ferroptosis. Surprisingly, we detected a greater abundance of Y-chromosome-bearing RSs (Y-RSs) than X-carrying RSs (X-RSs) in the aged testis, implying that X-RSs might be more prone to ferroptosis. Young mice fed a vitamin E (VE) deficient diet recapitulated age-related phenotypes, while VE supplementation prevented ferroptosis and promoted the survival of X-RSs in aged mice. Overall, this study reveals that aging causes ferroptosis in RSs, specifically impacting X-RSs, which can be prevented by VE supplementation, effectively reversing age-induced deterioration and contributing to healthy testicular aging.