bluuebunny/crossref_metadata_2025_split huggingface dataset:
Separate domains of theArabidopsisENHANCER OF PINOID drive its own polarization and recruit PIN1 to the plasma membrane
Authors: Matthes Michaela S. , Yun Nicole , Luichtl Miriam , Büschges Ulrich , Fiesselmann Birgit S. , Strickland Benjamin , Lehnardt Marietta S. , Ruiz Ramon A. Torres 
Published: March 2024

AbstractTheArabidopsisENHANCER OF PINOID (ENP) protein and the AGC-kinase PINOID (PID) synergistically impact on polarization of the auxin transporter PIN-FORMED1 (PIN1) required for plant leaf and flower organ development. ENP offers a PID-independent input for PIN-polarity sinceenp piddouble mutants lead to cotyledon- and flower-less plants in contrast topidsingle mutants, which develop cotyledons and abnormal albeit fertile flowers. This indicated that ENP, which depicts a similar polar localization as PIN1, is a potential interactor of PINs especially PIN1.Here we show that the modular structure of ENP predicted by AlphaFold separates the capability for its own cellular polarization and its function linked to polar PIN1 activity. The anterior part of ENP is subdivided into three structured domains. They are supportive and/or essential for cellular polarity. In contrast, the C-terminus, which is an intrinsically disordered region (IDR), is completely dispensable for polarity but essential for ENP-mediated PIN-function. FLIM-FRET shows ENP to be closely associated with the plasma membrane and its IDR to significantly interact with PINs. Moreover, the modification status of two prominent phosphorylation sites in the IDR determines ENPs stability and its capability in supporting PIN1. Our results show ENP to be an element in the assumed PIN-multiprotein complex and explain its impact on PID-independent PIN1 activity.
Large gradient of susceptibility to esca disease revealed by long-term monitoring of 46 grapevine cultivars in a common garden vineyard
Authors: Gastou Pierre , Destrac Irvine Agnès , Arcens Clarisse , Courchinoux Eva , This Patrice , van Leeuwen Cornelis , Delmas Chloé E. L. 
Published: March 2024

AbstractGrapevine (Vitis viniferaL.) is prone to many fungal diseases, including esca, a severe vascular disease threatening the wine sector and for which there is no cost-effective cure. Susceptibility to esca varies between cultivars in different infection conditions. It may therefore be possible to use the genetic diversity of grapevine cultivars to mitigate disease impact. However, the genetic component of esca susceptibility has rarely been investigated in the vineyard, and the specific mechanisms and varietal traits underlying esca susceptibility remain unknown.In this study, we monitored the incidence and severity of esca foliar symptoms and plant dieback (apoplexy and mortality) at plant level for seven years, on 46 cultivars planted in an experimental common garden, to separate the genetic component of esca susceptibility from the effects of environment and cropping practices. We observed a broad gradient of varietal susceptibility, with a mean incidence of 0 to 26% of vines expressing esca foliar symptoms depending on the variety. This gradient remained similar across years and, unlike the severity of foliar symptoms, the incidence of grapevine dieback was significantly correlated with that of foliar symptoms. We detected a significant but weak and very localised phylogenetic signal for the incidence of esca foliar symptoms in this panel of cultivars.We then explored the relationships between epidemiological metrics and ecophysiological and phenological traits phenotyped on the same plot. Esca disease incidence was negatively correlated with δ13C across cultivars, suggesting that varieties with higher water use efficiency are less prone to the expression of esca symptoms on leaves. Moreover, the least vigorous cultivars were among the least susceptible, although this relationship was not significant. By contrast, neither phenological stages nor nitrogen status were significantly predictive of cultivar susceptibility to the disease.Together, these results provide new insight into the potential of genetic resources for use in the sustainable management of grapevine trunk diseases and open up new perspectives for studying the pathological and physiological determinants of their incidence.
Setting Climate Targets: The Case of Higher Education and Research
Authors: Ligozat Anne-Laure , Brun Christophe , Demirdjian Benjamin , Gouget Guillaume , Jardé Emilie , Mialon Arnaud , Mouronval Anne-Sophie , Pagani Laurent , Vieu Laure 
Published: March 2024

AbstractThe carbon footprint and low-carbon strategies of higher education and research organizations have been the subject of scientific articles and reports. However, these provide few details on the reduction targets themselves, leaving the question of how should higher education and research organizations define and construct their climate targets and trajectories unanswered. The present paper fills this gap. We first review and analyze the documents describing the climate strategies of 53 higher education and research organizations coming from 11 countries, based on their detailed GreenHouse Gas emissions (GHGs) reporting. The selected reports include at least one target re-duction for at least one target year. Then, on the basis of this analysis we propose guidelines to encourage and help higher education and research organizations set rele-vant climate targets.
Karanjin alters gene expression through ERα: a preliminary study
Authors: Bhatt Gaurav , Rangan Latha , Limaye Anil Mukund 
Published: March 2024

AbstractKaranjin is an abundant furanoflavonoid-constitutent of pongamia oil. Among several biological actions of karanjin, the antiproliferative effect of karanjin has gained traction in the recent years; raising speculations about its anticancer potential. In the backdrop of partial estrogen-like alteration of gene expression by karanjin in ERα positive MCF-7 breast cancer cells, we present preliminary evidences supporting of the role of ERα in karanjin-mediated effects.
The Kv2.2 channel mediates the inhibition of Prostaglandin E2 on glucose-stimulated insulin secretion in pancreatic β-cells
Authors: Pan Chengfang , Liu Ying , Wang Liangya , Fan Wengyong , Ni Yunzhi , Zhang Xuefeng , Wu Di , Li Chenyang , Li Jin , Li Zhaoyang , Liu Rui , Hu Changlong 
Published: March 2024

AbstractProstaglandin E2 (PGE2) is an endogenous inhibitor of glucose-stimulated insulin secretion (GSIS) and plays an important role in pancreatic β-cell dysfunction in type 2 diabetes mellitus (T2DM). This study aimed to explore the underlying mechanism by which PGE2 inhibits GSIS. Our results showed that PGE2 inhibited Kv2.2 channels via increasing PKA activity in HEK293T cells overexpressed with Kv2.2 channels. Point mutation analysis demonstrated that S448 residue was responsible for the PKA-dependent modulation of Kv2.2. Furthermore, the inhibitory effect of PGE2 on Kv2.2 was blocked by EP2/4 receptor antagonists, while mimicked by EP2/4 receptor agonists. The immune fluorescence results showed that EP1-EP4 receptors are expressed in both mouse and human β-cells. In INS-1(832/13) β-cells, PGE2 inhibited voltage-gated potassium currents and electrical activity through EP2/4 receptors and Kv2.2 channels. Knockdown of Kv2.2 reduced the action potential firing frequency and alleviated the inhibition of PGE2 on GSIS in INS-1(832/13) β-cells. PGE2 impaired glucose tolerance in wild-type mice but did not alter glucose tolerance in Kv2.2 knockout mice. Knockout of Kv2.2 reduced electrical activity, GSIS and abrogated the inhibition of PGE2 on GSIS in mouse islets. In conclusion, we have demonstrated that PGE2 inhibits GSIS in pancreatic β-cells through the EP2/4-Kv2.2 signaling pathway. The findings highlight the significant role of Kv2.2 channels in the regulation of β-cell repetitive firing and insulin secretion, and contribute to the understanding of the molecular basis of β-cell dysfunction in diabetes.
Root exudation and rhizosphere microbial recruitment are influenced by novel plant trait diversity in carrot genotypes
Authors: Anderson Hannah M. , Cagle Grace A. , Majumder Erica L.-W. , Silva Erin , Dawson Julie , Simon Philipp , Freedman Zachary B. 
Published: March 2024

AbstractRoot exudate composition can influence rhizosphere microbial recruitment and is tightly controlled by plant genetics. However, little research has profiled root exudate in vegetable crops or determined their role in rhizosphere microbial community and metabolite composition. It is also not well understood how root exudates and resulting rhizosphere dynamics shift across plant trait diversity and with the development of novel crop genotypes. To address these knowledge gaps, this study paired metabolomics and microbiome analyses to evaluate associations between the composition of exudates, soil bacterial and fungal communities, and soil metabolites across four genotypes of organically produced carrot of differential breeding histories, including two experimental genotypes. Plant genotypes modified soil microbial diversity and composition, and differentially recruited bacterial taxa with demonstrated potential for plant-growth related functions including ammonia oxidation, nitrogen fixation, and phytohormone production. Bacterial rhizosphere recruitment from bulk soil was genotype and root exudate-mediated, while fungal recruitment was not. Moreover, root exudate composition was distinct in an heirloom genotype and a novel nematode resistant genotype, compared to other genotypes tested. Root exudate and rhizosphere metabolite composition was decoupled, and soil metabolites strongly associated with fungal, but not bacterial communities. Taken together, the results of this study suggest that novel crop trait diversity and breeding histories hold consequences for the functional potential of soils through the diversification of root exudate mediated plant-microbe interactions.
PRMT5 maintains tumor stem cells to promote pediatric high-grade glioma tumorigenesis
Authors: DeSisto John , Balakrishnan Ilango , Knox Aaron J. , Link Gabrielle , Venkataraman Sujatha , Vibhakar Rajeev , Green Adam L. 
Published: March 2024

AbstractBackgroundPediatric high-grade gliomas (PHGG) are aggressive, undifferentiated CNS tumors with poor outcomes, for which no standard-of-care drug therapy currently exists. Through a screen for epigenetic regulators, we identifiedPRMT5as essential for PHGG growth. We hypothesized that, similar to its effect in normal cells, PRMT5 promotes self-renewal of stem-like PHGG tumor initiating cells (TICs) essential for tumor growth.Methods. We conductedin vitroassays, including limiting dilution studies of self-renewal, to determine the phenotypic effects ofPRMT5KD. We performed ChIP-Seq to identify PRMT5-mediated epigenetic changes and gene set enrichment analysis to identify pathways that PRMT5 regulates. Using an orthotopic xenograft model of PHGG, we tracked survival and histological characteristics resulting fromPRMT5KD or administration of a PRMT5 inhibitor ± radiation therapy (RT).ResultsIn vitro,PRMT5KD slowed cell cycle progression, tumor growth and self-renewal.PRMT5KD reduced H3K4me3 occupancy at genes associated with self-renewal, tumor formation and growth.In vivo,PRMT5KD increased survival and reduced tumor aggressiveness; however, pharmacological inhibition of PRMT5 with or without RT did not improve survival.ConclusionPRMT5KD epigenetically reduced TIC self-renewal, leading to increased survival in preclinical models. Pharmacological inhibition of PRMT5 enzymatic activity may have failedin vivodue to insufficient reduction of PRMT5 activity by chemical inhibition, or this failure may suggest that non-enzymatic activities of PRMT5 are more relevant.ImplicationsOur findings show the importance ofPRMT5to maintain and promote the growth of stemlike cells that initiate and drive tumorigenesis in pediatric high grade glioma.
playOmics: A multi-omics pipeline for interpretable predictions and biomarker discovery
Authors: Głowacka-Walas Jagoda , Sijko Kamil , Wojdan Konrad , Gambin Tomasz 
Published: March 2024

AbstractBackgroundMulti-omics analysis is increasingly popular in biomedical research. While promising, these analyses confront challenges in data integration, management, and interpretation due to their complexity, diversity, and volume. Moreover, achieving transparency, reproducibility, and repeatability in multi-omics analyses is essential for facilitating scientific collaboration and validation of complex datasets.ResultsWe introduce playOmics, an open-source R package tailored for omics data analysis. It facilitates data management and biomarker discovery through various visualizations, statistics and explanations for boosted interpretability. playOmics identifies significant prognostic markers and iteratively constructs logistic regression models, identifying combinations with high predictive performance. Our tool enables users to make direct, model-driven predictions by inputting new data into the selected pre-trained model. playOmics performed well in handling extensive datasets and missing data, showing a mean validation MCC of 0.773.ConclusionsplayOmics demonstrates the balance between model complexity and interpretability, crucial in biomedical research for understanding model decisions. playOmics’ approach promotes a flexible model selection process, encouraging exploration and hypothesis generation in biomarker discovery. The dockerized setup and intuitive graphical interface of playOmics support its adoption in a wide range of research and clinical settings, adhering to principles of open science, enhancing reproducibility and transparency.
Magnetic particle imaging reveals that iron-labeled extracellular vesicles accumulate in brains of mice with metastases
Authors: Toomajian Victoria A , Tundo Anthony , Ural Evran E , Greeson Emily M , Contag Christopher H , Makela Ashley V 
Published: March 2024

AbstractThe incidence of breast cancer remains high worldwide and is associated with a significant risk of metastasis to the brain that can be fatal; this is due, in part, to the inability of therapeutics to cross the blood brain barrier (BBB). Extracellular vesicles (EVs) have been found to cross the BBB and further, have been used to deliver drugs to tumors. EVs from different cell types appear to have different patterns of accumulation and retention as well as efficiency of bioactive cargo delivery to recipient cells in the body. Engineering EVs as delivery tools to treat brain metastases, therefore, will require an understanding of the timing of EV accumulation, and their localization relative to metastatic sites. Magnetic particle imaging (MPI) is a sensitive and quantitative imaging method that directly detects superparamagnetic iron. Here, we demonstrate MPI as a novel tool to characterize EV biodistribution in metastatic disease after labeling EVs with superparamagnetic iron oxide (SPIO) nanoparticles. Iron-labeled EVs (FeEVs) were collected from iron-labeled parental primary 4T1 tumor cells and brain-seeking 4T1BR5 cells, followed by injection into mice with orthotopic tumors or brain metastases. MPI quantification revealed that FeEVs were retained for longer in orthotopic mammary carcinomas compared to SPIOs. MPI signal due to iron could only be detected in brains of mice bearing brain metastases after injection of FeEVs, but not SPIOs, or FeEVs when mice did not have brain metastases. These findings indicate the potential use of EVs as a therapeutic delivery tool in primary and metastatic tumors.TOC Graphic
An array ofZymoseptoria triticieffectors suppress plant immune responses
Authors: Thynne E. , Ali H. , Seong K. , Abukhalaf M. , Guerreiro M. A. , Flores-Nunez V. M. , Hansen R. , Bergues A. , Salman M. J. , Rudd J. J. , Kanyuka K. , Tholey A. , Krasileva K. V. , Kettles G. J. , Stukenbrock E. H. 
Published: March 2024

AbstractZymoseptoria triticiis the most economically significant fungal pathogen of wheat in Europe. However, despite the importance of this pathogen, the molecular interactions between pathogen and host during infection are not well understood. Herein, we describe the use of two libraries of clonedZ. triticieffectors that were screened to identify effector candidates with putative pathogen associated molecular pattern (PAMP) triggered immunity (PTI)-suppressing activity. The effectors from each library were transiently expressed inNicotiana benthamiana, and expressing leaves were treated with bacterial or fungal PAMPs to assess the effectors’ ability to suppress reactive oxygen species (ROS) production. From these screens, numerous effectors were identified with PTI-suppressing activity. In addition, some effectors were able to suppress cell death responses induced by otherZ. triticisecreted proteins. We used structural prediction tools to predict the putative structures of all of theZ. triticieffectors, and used these predictions to examine whether there was enrichment of specific structural signatures among the PTI-suppressing effectors. From among the libraries, multiple members of the killer protein-like 4 (KP4) and killer protein-like 6 (KP6) effector families were identified as PTI-suppressors. This observation is intriguing, as these protein families were previously associated with antimicrobial activity rather than virulence or host manipulation. This data provides mechanistic insight into immune suppression byZ. triticiduring infection, and suggests that similar to biotrophic pathogens, this fungus relies on a battery of secreted effectors to suppress host immunity during early phases of colonisation.
Small molecule and cell contact-inducible systems for controlling expression and differentiation in stem cells
Authors: Soliman Sarah S. , Shah Devan H. , El-Samad Hana , Weinberg Zara Y. 
Published: March 2024

AbstractSynthetic developmental biology uses engineering approaches to understand multicellularity with goals ranging from recapitulating development to building synthetic organisms. Current approaches include engineering multicellular patterning, controlling differentiation, and implementing cooperative cellular behaviors in model systems. Synthetic biology tools enable these pursuits with genetic circuits that drive customized responses to arbitrary stimuli, synthetic receptors that enable orthogonal signaling channels, and light- or drug-inducible systems that enable precise spatial and temporal control of cell function. Mouse embryonic stem cells (mESCs) offer a well-studied and genetically tractable pluripotent chassis for pursuing synthetic development questions however, there is minimal characterization of existing synthetic biology tools in mESCs and we lack genetic toolkits for rapid iterative engineering of synthetic development workflows. Here, we began to address this challenge by characterizing small molecule and cell contact-inducible systems for gene expression in and differentiation of mESCs. We show that small molecule and cell-contact inducible systems work reliably and efficiently for controlling expression of arbitrary genetic payloads. Furthermore, we show that these systems can drive direct differentiation of mESCs into neurons. Each of these systems can readily be used on their own or in combination, opening many possibilities for studying developmental principles with high precision.
Functional genetics reveals modulators of anti-microtubule drug sensitivity
Authors: Su Kuan-Chung , Radul Elena , Maier Nolan K , Tsang Mary-Jane , Goul Claire , Moodie Brittania , Keys Heather R. , Cheeseman Iain M 
Published: March 2024

AbstractMicrotubules play essential roles in diverse cellular processes and are important pharmacological targets for treating human disease. Here, we sought to identify cellular factors that modulate the sensitivity of cells to anti-microtubule drugs. We conducted a genome-wide CRISPR/Cas9-based functional genetics screen in human cells treated with the microtubule-destabilizing drug nocodazole or the microtubule-stabilizing drug taxol. We further conducted a focused secondary screen to test drug sensitivity for ∼1400 gene targets across two distinct human cell lines and to additionally test sensitivity to the Kif11-inhibitor, STLC. These screens defined gene targets whose loss enhances or suppresses sensitivity to anti-microtubule drugs. In addition to gene targets whose loss sensitized cells to multiple compounds, we observed cases of differential sensitivity to specific compounds and differing requirements between cell lines. Our downstream molecular analysis further revealed additional roles for established microtubule-associated proteins and identified new players in microtubule function.
Adaptive landscapes unveil the complex evolutionary path to mammalian forelimb function and posture
Authors: Brocklehurst Robert J. , Mercado Magdalen , Angielczyk Kenneth D. , Pierce Stephanie E. 
Published: March 2024

AbstractThe ‘sprawling-parasagittal’ postural transition is a key part of mammalian evolution, associated with sweeping reorganization of the postcranial skeleton in mammals compared to their forebears, the non-mammalian synapsids. However, disputes over forelimb function in fossil synapsids render the precise nature of the ‘sprawling-parasagittal’ transition controversial. We shed new light on the origins of mammalian posture, using evolutionary adaptive landscapes to integrate 3D humerus shape and functional performance data across a taxonomically comprehensive sample of fossil synapsids and extant comparators. We find that the earliest pelycosaur-grade synapsids had a unique mode of sprawling, intermediate between extant reptiles and monotremes. Subsequent evolution of synapsid humerus form and function showed little evidence of a direct progression from sprawling pelycosaurs to parasagittal mammals. Instead, posture was evolutionarily labile, and the ecological diversification of successive synapsid radiations was accompanied by variation in humerus morphofunctional traits. Further, synapsids frequently evolve towards parasagittal postures, diverging from the reconstructed optimal evolutionary path; the optimal path only aligns with becoming increasingly mammalian in derived cynodonts. We find the earliest support for habitual parasagittal postures in stem therians, implying that synapsids evolved and radiated with distinct forelimb trait combinations for most of their recorded history.