bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular and mitochondrial effects of a gold-N Heterocyclic Carbene on LNCaP and PC3 prostate cancer cell lines
Authors: Eguida Sangouard Judith , Cheron Mathilde , Rivrais Guillaume , Alziari Serge , Cisnetti Federico , Gautier Arnaud , Garreau-Balandier Isabelle , Vernet Patrick 
Published: January 2025

AbstractThe discovery of cisplatin and its anti-tumor activities but also its side-effects led to the development of new cytotoxic metal complexes. Metal-based compounds and especially gold N-heterocyclic carbene complexes have shown their antitumoral activities and present a great interest of use in medicine. These metallodrugs have been shown to target nuclear DNA, but also other organelles such as mitochondria. The mechanisms of action have been studied and would involve the triggering of cell death, in particular by apoptosis, highlighting mitochondrial dysfunctions. The organometallic compound used in this study has been characterized by its IC50and GI50in two prostatic cancer cell lines (LNCaP and PC3). Its capacity to enter the cells and particularly mitochondria was also analyzed. Furthermore, its effects on several parameters (proliferation, cell death, cell cycle) have been determined in vitro. The compound displayed a cytotoxic effect (IC50< 5µM) confirmed by the MTT assays and cell death analysis by flow cytometry. It also displayed a cytostatic effect confirmed by the determination of the GI50, and induced a brief cell cycle arrest, depending on the cell line and the metallocarbene concentration. Furthermore, the incubation with the gold N-heterocyclic carbene led to mitochondrial membrane potential changes and decreased the accumulation of the mitochondrial protein Rieske. All our results show a global cytotoxic and cytostatic effects of the gold N-heterocyclic carbene that can involve mitochondria.
Battery-powered Wearable Utilizing Flexible Printed Circuit-based Organic Electrochemical Transistor Embedded with Simple Circuits of Voltage Divider and Regulator for Biosignal Measurement
Authors: Yeung Sin Yu , Lin Haosi , Li Yue , Fung Cheuk Wang , Nyein Hnin Yin Yin , Hsing I-Ming 
Published: January 2025

AbstractWith the distinctive advantages of high transconductance, low operating voltage, mixed ionic-electronic conductivities, and dynamic versatility, organic electrochemical transistor (OECT) has emerged as a promising wearable technology capable of measuring various biophysical and biochemical signals. Despite the intensive research efforts towards enhancing its wearability, challenges related to signal conversion, voltage sourcing, and manufacturing scalability are seldom addressed. Herein, we report a compact and easy-to-build integrated module that provides stable biasing from batteries while enabling current-to-voltage conversion and additional amplification of OECT’s responses. Given the known amplitude of target signals, transistor bias and amplification gain can be adjusted easily on site by tuning two key resistance values and ensuring sufficient battery voltage. Furthermore, the flexible OECTs in this work were fabricated through an industrial manufacturing process for flexible printed circuits (FPC), in which the polymeric channel material and device architecture were both customized to accommodate the fabrication constraints. Notably, preliminary measurements based on the battery-powered unit comprising our OECT and module demonstrate significantly amplified bio-signals compared to electrodes. The successful acquisition of on-body electrocardiogram voltages further underscores the potential of this platform to support current and future OECT interfaces.
TRIP13 protects pancreatic cancer cells against intrinsic and therapy-induced DNA replication stress
Authors: Anand Jay R. , Droby Gaith N. , Joseph Sayali , Patel Urvi , Zhang Xingyuan , Klomp Jeffrey A. , Der Channing J. , Purvis Jeremy E. , Wolff Samuel C. , Bowser Jessica , Vaziri Cyrus 
Published: January 2025

ABSTRACTOncogene activation in normal untransformed cells induces DNA replication stress and creates a dependency on DNA Damage Response (DDR) mechanisms for cell survival. Different oncogenic stimuli signal via distinct mechanisms in every cancer setting. The DDR is also pathologically re-programmed and deployed in diverse ways in different cancers. Because mutant KRAS is the driver oncogene in 90% of Pancreatic Ductal Adenocarcinomas (PDAC), here we have investigated DDR mechanisms by which KRAS-induced DNA replication stress is tolerated in normal human pancreatic epithelial cells (HPNE). Using a candidate screening approach, we identify TRIP13 as a KRASG12V-induced mRNA that is also expressed at high levels in PDAC relative to normal tissues. Using genetic and pharmacological tools, we show that TRIP13 is necessary to sustain ongoing DNA synthesis and viability specifically in KRASG12V-expressing cells. TRIP13 promotes survival of KRASG12V-expressing HPNE cells in a Homologous Recombination (HR)-dependent manner.KRASG12V-expressing HPNE cells lacking TRIP13 acquire hallmark HR-deficiency (HRD) phenotypes including sensitivity to inhibitors of Trans-Lesion Synthesis (TLS) and Poly-ADP Ribose Polymerase (PARP).Established PDAC cell lines are also sensitized to intrinsic DNA damage and therapy-induced genotoxicity following TRIP13-depletion. Taken together our results expose TRIP13 as an attractive new and therapeutically-tractable vulnerability of KRAS-mutant PDAC.
The dominant lineage ofPhakopsora pachyrhiziin the United States of America does not have a Brazilian origin
Authors: Ferreira Everton Geraldo Capote , Inoue Yoshihiro , Murithi Harun M , Nardwattanawong Tantawat , Cheema Jitender , Grootens Ruud , Paes Sirlaine Albino , Mahuku George , Joosten Matthieu H A J , Hartman Glen , Yamaoka Yuichi , Catherine Aime M , Brommonschenkel Sérgio H , van Esse H Peter , Gupta Yogesh K 
Published: January 2025

SummaryAsian soybean rust (ASR), caused by the obligate biotrophic fungus,Phakopsora pachyrhizi,was first reported in the continental United States of America (USA) in 2004 and over the years has been of concern to soybean production in the USA. The prevailing hypothesis is thatP. pachyrhizispores were introduced into the USA via hurricanes originating from South America, particularly Hurricane Ivan.To investigate the genetic diversity and global population structure ofP. pachyrhizi,we employed exome-capture based sequencing on 84 field isolates collected from different geographic regions worldwide. We compared the gene-encoding regions from all these field isolates and found that four major haplotypes are prevalent worldwide. Here, we provide genetic evidence supporting multiple incursions that have led to the currently establishedP. pachyrhizipopulation of the USA. Phylogenetic analysis of mitochondrial genes further supports this hypothesis.Notably, we observed limited genetic diversity inP. pachyrhizipopulations in Brazil, suggesting a clonal population structure in that country that contrasts to populations from the USA and Africa.This study provides the first comprehensive characterization ofP. pachyrhizipopulation structures defined by genetic evidence from populations across major soybean growing regions.
Comparative Analysis of Phytochemical Constituents ofGinkgo BilobaFlowers and Leaves, and Evaluation of Their Biological Activities
Authors: Wang Yu-Ying , Li Rui-Hong , Sun Xin , Xia Zi-Ming , Zhang Guang-Jie , Li Bin , Tian Ying , Li Min , Liu Shu-Chen 
Published: January 2025

AbstractBackgroundsGinkgo bilobaL. has attracted much attention for its unique chemical composition and pharmacological properties, and most of the research focused onGinkgo bilobaleaves (GBL). Our preliminary research found thatGinkgo bilobaflowers (GBF) were superior to GBL in terms of anti-radiation activity, but the underlying cause of this discrepancy in activity remains elusive.ObjectivesThe aim of this study was to systematically compare the chemical and nutritional composition ofGinkgo bilobaflowers and leaves, to further elucidate the material basis of the medicinal and nutritional value ofGinkgo bilobaflowers, and to conduct further comparative studies on the anti-ferroptosis activity and anti-radiation activity of the two.MethodsIn this study, the chemical constituents of GBF and GBL were identified by UPLC-Q-orbitrap HRMS, and the contents of amino acids, fatty acids, inorganic elements, purines, and ceramides of both were determined. Meanwhile, the anti-iron death activity and anti-radiation activity of GBF and GBL were comparatively studied by cellular experiments.ResultsThe results showed that the content of chemical components such as flavonoids and other nutrients such as amino acids, fatty acids, and ceramides were richer in GBF than in GBL, and GBF was indeed superior to GBL in terms of anti-radiation and anti-ferroptosis activity.ConclusionThrough in-depth analyses of the chemical and nutritional compositions ofGinkgo bilobaflowers and leaves, the present study reveals the possible material basis for the stronger activity of GBF and provides theoretical support for its application in nutraceuticals and pharmaceuticals, especially in the development of functional nutraceuticals and anti-radiation drugs with higher health benefits.
Gene regulatory mechanisms guiding bifurcation of inhibitory and excitatory neuron lineages in the anterior brainstem
Authors: Kilpinen Sami , Virtanen Lassi , Bodington-Celma Silvana , Bonsdorff Amos , Heliölä Heidi , Achim Kaia , Partanen Juha 
Published: January 2025

AbstractSelector transcription factors control choices of alternative cellular fates during development. The ventral rhombomere 1 of the embryonic brainstem produces neuronal precursors that can differentiate into either inhibitory GABAergic or excitatory glutamatergic neurons important for the control of behaviour. Transcription factors (TFs)Tal1,Gata2andGata3are required for adopting the GABAergic neuronal identity and inhibiting the glutamatergic identity. Here, we asked how these selector TFs are activated and how they control the identity of the developing brainstem neurons. We addressed these questions by analysing chromatin accessibility at putative gene regulatory elements active during GABAergic and glutamatergic neuron lineage bifurcation, combined with studies of transcription factor expression and DNA-binding. Our results show that theTal1,Gata2andGata3genes are activated by highly similar mechanisms, with connections to regional patterning, neurogenic cell cycle exit and general course of neuronal differentiation. After activation,Tal1,Gata2andGata3are linked by auto- and cross-regulation as well as regulatory interactions with transcription factors of the glutamatergic branch. Predicted targets of these selector TFs include genes expressed in GABAergic neurons, glutamatergic neurons, or both. Unlike genes specific to the glutamatergic branch, the genes expressed in GABAergic neurons appear to be under combinatorial control ofTal1,Gata2andGata3. Understanding gene regulatory interactions affecting the anterior brainstem GABAergic and glutamatergic neuron differentiation may give genetic and mechanistic insights into neurodevelopmental traits and disorders.
Endothelial Cu Uptake Transporter CTR1 Senses Disturbed Flow to Promote Atherosclerosis through Cuproptosis
Authors: Sudhahar Varadarajan , Xiao Zhen , Das Archita , Ash Dipankar , Yadav Shikha , Matier Carson D. , Pezacki Aidan T. , Chatterjee Barun , Antipova Olga A. , Vogt Stefan , McMenamin Malgorzata , Kelley Stephanie , Csanyi Gabor , Lee Jaekwon , Jo Hanjoong , Chang Christopher J. , Rao Jianghong , Kaplan Jack H. , Ushio-Fukai Masuko , Fukai Tohru 
Published: January 2025

ABSTRACTEndothelial cells (ECs) lining blood vessels sense disturbed blood flow (D-flow), which drives mitochondrial dysfunction and atherosclerosis. Copper (Cu) is an essential micronutrient, and its disruption of homeostasis has been implicated in atherosclerosis. Cellular Cu levels are tightly controlled by Cu transport proteins including the Cu importer CTR1. Cuproptosis is a recently discovered form of regulated cell death triggered by mitochondrial Cu accumulation, but its endogenous stimulants and role in atherosclerosis remain unknown. Using EC-specific CTR1-deficient mice and cultured ECs, we show that endothelial CTR1 responds to D-flow by increasing mitochondrial Cu levels through its interaction with the mitochondrial Cu transporter SLC25A3 at caveolae/lipid rafts. This leads to the aggregation of lipoylated mitochondrial proteins, mitochondrial dysfunction, and cuproptosis, thereby exacerbating atherosclerosis. Importantly, mitochondria-targeted Cu-chelating nanoparticles effectively mitigate D-flow-induced cuproptosis and atherosclerosis, highlighting the endothelial CTR1-SLC25A3-mitochondrial Cu axis as a potential therapeutic target.
Dominant species determinesDrosophila-parasitoid food web dynamics and stability more strongly than complexity, warming or invasion
Authors: Ximenez-Embun Miguel G. , Proudhom Gregoire , Thierry Mélanie , Pardikes Nicholas A. , Mácová Anna , Hrček Jan 
Published: January 2025

AbstractEcological communities face major challenges of biodiversity loss, invasive species, and warming due to human action. Factors that determine the dynamics, stability and functioning of network of interacting species have been debated in ecology since its beginning as discipline. Community complexity and dominant (keystone) species have been proposed as the most relevant factors, however there is lack of knowledge on how these factors will interact with warming and invasion. To determine the effect of complexity, warming or invasion and their combinations on stability and functioning of a food web we performed a microcosm laboratory experiment usingDrosophila-parasitoid food webs as a model. During five months, we recorded the dynamics of twelve different food webs (different combinations of flies and parasitoid species with two complexity levels) subjected to two temperature regimes (ambient and warming) and invasion or not byDrosophila suzukiiin a factorial design. We did not observe any major effect of complexity or invasion. However, species composition had major effect, as webs withDrosophila simulanspresent were rapidly dominated by it, reducing diversity, increasing parasitism rate, reducing stability and bringing the community on the verge of collapse. Warming in turn increased diversity, overall fly population and temporal stability, while decreasing parasitism rate. Invasion ofD. suzukiiwas not successful in any of the networks, possibly due to its low competitive ability. Our results imply that dominant species can have very strong effects on dynamics and stability, compared to food web complexity.
Symmetry as a Fundamental Principle in Defining Gene Expression and Phenotypic Traits
Authors: Zhang Cheng , Correia Cristina , Weiskittel Taylor , Tan Shyang-Hong , Zhang Zhuofei , Yeo Kok-Siong , Zhu Shizhen , Ung Choong-Yong , Li Hu 
Published: January 2025

ABSTRACTSymmetry refers to properties that remain invariant upon mathematical transformations. The principles of symmetry have guided numerous important discoveries in physics and chemistry but not in biology and medicine. Here, we aim to explore the presence of symmetry relationships at the gene expression level as a mean to distinguish between healthy and disease states. We deployed Learning-Based Invariant Feature Engineering - LIFE, a hybrid machine learning approach implemented with two symmetric invariant feature functions (IFFs) to identify Invariant Feature Genes (IFGs), which are gene pairs whose IFF single-value outputs remain invariant across individual samples in a given biological phenotype. Our multiclass classification results across the transcriptomes of 25 normal organs, 25 cancer types, and blood samples obtained from 4 different types of neurodegenerative diseases revealed the presence of unique phenotype-specific IFGs. We constructed networks using these IFGs (IF-Nets) and intriguingly, we demonstrated that the hubs could serve as information encoders, capable of reconstructing sample-wise expression values in relation to their counterpart genes. More importantly, we found that hubs of cancer IF-Nets were enriched with both approved and clinical trial drugs, highlighting “symmetry breaking” as a novel approach for treating diseases.
Decoding human placental cellular and molecular responses to maternal obesity and fetal growth
Authors: Jiang Hong , Derisoud Emilie , Parreira Denise , Taebnia Nayere , Jannig Paulo R. , Shafagh Reza Zandi , Zhao Allan , Li Congru , Ortiz Macarena , Maliqueo Manuel Alejandro , Stener-Victorin Elisabet , Lauschke Volker M. , Deng Qiaolin 
Published: January 2025

AbstractObesity poses risks to maternal health and increases the likelihood of short– and long-term adverse pregnancy outcomes in the offspring. The placenta, a key organ at the maternal-fetal interface, responds to maternal obesity and regulates fetal growth. To investigate the molecular features of physiological adaptation, we perform single-nuclei RNA-seq on human placentas and compared the transcriptomic profiles of women with obesity delivering appropriate-or large-for-gestational age (i.e., AGA and LGA) babies with those from normal-weight healthy controls delivering AGA babies. Commonness-score metric is developed to identify responses attributable to maternal obesity effects or fetal growth. We find hypoxia and induction of TNF-α signaling in syncytiotrophoblasts, while the receptor tyrosine kinases are down-regulated in cytotrophoblasts in maternal obesity irrespective of fetal growth. Notably, we identify that the fine-tune of PI3K-AKT and MAPK cascade signaling pathways in cytotrophoblasts underlies AGA versus LGA. Hofbauer cells upregulate immunometabolic genes specifically in LGA outcomes and also express most of the ligands detected only in placentas of LGA. Finally, we also use a novel microfluidic organs-on-a-chip device fabricated for co-culturing adipose spheroids and trophoblast organoids. This system recapitulates some responses of syncytiotrophoblasts to maternal obesity, offering a functionally relevant reductionistic system to study maternal-placental interaction. Our findings deconvolute key cellular and molecular adaptation of the placenta to maternal obesity and fetal overgrowth in physiological condition.
SimdMinimizers: Computing random minimizers,fast
Authors: Groot Koerkamp Ragnar , Martayan Igor 
Published: January 2025

AbstractMotivationBecause of the rapidly-growing amount of sequencing data, computingsketchesof large textual datasets has become an essential preprocessing task. These sketches are typically much smaller than the input sequences, but preserve sufficient information for downstream analysis.Minimizersare an especially popular sketching technique and used in a wide variety of applications. They sample at least one out of everywconsecutivek-mers. As DNA sequencers are getting more accurate, some applications can afford to use a largerwand hence sparser and smaller sketches. And as sketches get smaller, their analysis becomes faster, so the time spent sketching the full-sized input becomes more of a bottleneck.MethodsOur librarysimd-minimizersimplements a random minimizer algorithm using SIMD instructions. It supports both AVX2 and NEON architectures. Its main novelty is two-fold. First, it splits the input into 8 chunks that are streamed over in parallel through all steps of the algorithm. This is enabled by using the completely deterministictwo-stackssliding window minimum algorithm, which seems not to have been used before for finding minimizers.ResultsOur library is up to 9.5× faster than a scalar implementation of therescanmethod whenw= 5 is small, and 4.5× faster for largerw= 19. Computingcanonicalminimizers is only around 50% slower than computing forward minimizers, and around 16× faster than the existing implementation in theminimizer-itercrate. Our library finds all (canonical) minimizers of a 3.2Gbp human genome in 4.1 (resp. 6.0) seconds.Supplementary MaterialSoftware:https://github.com/rust-seq/simd-minimizersFundingRagnar Groot Koerkamp: ETH Research Grant ETH-1721-1 to Gunnar Rätsch.Igor Martayan: ENS Rennes Doctoral Grant.
A short cut to sample coverage standardization in meta-barcoding data provides new insights into land use effects on insect diversity
Authors: Kortmann Mareike , Chao Anne , Chiu Chun-Huo , Heibl Christoph , Mitesser Oliver , Morinière Jérôme , Bozicevic Vedran , Hothorn Torsten , Rothacher Julia , Englmeier Jana , Ewald Jörg , Fricke Ute , Ganuza Cristina , Haensel Maria , Moning Christoph , Redlich Sarah , Rojas-Botero Sandra , Tobisch Cynthia , Uhler Johannes , Zhang Jie , Steffan-Dewenter Ingolf , Müller Jörg 
Published: January 2025

AbstractThe use of metabarcoding for insect species identification has grown rapidly, but the absence of abundance data hinders meaningful diversity metrics like sample coverage-standardized species richness. Additionally, the vast number of taxa often lacks a unified phylogeny or trait database. We present a framework for constructing a phylogenetic tree encompassing the majority of insect families, standardisation of sample coverage (an objective measure of sample completeness) and assessment of both taxonomic and phylogenetic diversity using the Hill series for metabarcoding data. Applied to central Europe, our framework analysed insect diversity from 400 families along a land-use gradient. Results revealed land-use intensity significantly affects sample coverage, emphasizing the need for biodiversity standardization. After standardization, taxonomic diversity declined by 27–44%, and phylogenetic diversity by 13–29% across 39,000 Operational Taxonomic Units, from forests to agricultural areas. Rare species exhibited greater phylogenetic diversity loss than taxonomic, while dominant species showed smaller phylogenetic losses but stronger declines in taxonomic diversity. Our findings underscore agriculture’s detrimental effects on specific insect taxa, even after adjusting for sample coverage, and provide new insights into the loss of functional diversity, as represented by phylogeny.
Do it yourself: Creating 3D brain-surface models and custom-made brain matrices for guided sectioning using photogrammetry and three-dimensional printing technology
Authors: Holtz Sophie , Hechavarria Julio , Knörnschild Mirjam , Scharff Constance 
Published: January 2025

AbstractNeuroethologists study many non-model animals. The development of techniques for precise and standardized histological brain analysis is key for understanding neural mechanisms across species. Here we present a novel cost-effective approach combining photogrammetry and three-dimensional printing technology to generate 3D brain surface models and produce species-specific brain matrices for precise and reproducible trimming, blocking, and sectioning of brain tissue. Using this strategy, we generated the first 3D brain surface model and brain matrix for Seba’s short-tailed fruit batCarollia perspicillata, CP. We generated the 3D brain surface model with the open-source 3D graphics suite Blender and its inexpensive photogrammetry plug-in Snapmesh. High-quality photographs of two maleCPbrains were used for the 3D-reconstruction, resulting in a 3D surface model. Photogrammetry thus offers a viable, cheap alternative to techniques otherwise requiring access to costly 3D- or CT-scanners. The brain matrix was then modeled using Blender, and printed using a 3D printer. Our brain matrix facilitates and standardizes trimming or blocking of brains, providing consistent access to brain regions ofCPin the sagittal and coronal planes. Using this workflow, brain surface models and brain matrices can be produced from brains without tissue loss. Our approach provides an affordable, and tissue-preserving alternative for the generation of 3D brain surface models and brain matrices and will benefit researchers globally, especially those with limited funding, no access to scanners or working with particularly valuable specimen.