bluuebunny/crossref_metadata_2025 huggingface dataset:
Theta oscillations dictate the evolution of memories across periods of sleep or wakefulness
Authors: Denis Dan , Chen Zhiyi , Kaur Manroop , Clayden Ben , Schreiner Thomas , Cairney Scott A
Published: January 2025

Every day, we are exposed to an enormity of information. But how does the brain select which experiences to strengthen into long-term memories? Using scalp electroencephalography in human participants, we find evidence that memories are tagged at encoding for selective strengthening across sleep or wakefulness. For memories retained over sleep, this process was driven by 3-8 Hz theta rhythms at learning, with the magnitude of this theta response predicting the coupling of slow oscillations to sleep spindles in later sleep (an established neural correlate of sleep-dependent memory processing). In turn, slow oscillation-spindle coupling was associated with superior memory retention at a post-sleep test. These findings offer new insights into the neural mechanisms through which our brains determine which information is retained for the future.
YTHDF3 promotes the progression of gastric cancer by activating Wnt/β-catenin signaling pathway via targeting NEK7
Authors: Sun Xiaoran , Han Shuangshuang , Liu Kunyi , Si Yi , Xuan Mingda , Zhang Rui , Jiao Jiao , Liu Ting , Yu Weifang , Wang Jia
Published: January 2025

Gastric cancer is a widespread and deadly malignancy among global digestive tract tumors, alarmingly ranking as the fifth most common cancer in terms of incidence and mortality. Our research, utilizing immunohistochemistry and qRT-PCR, revealed a significant upregulation of YTHDF3 in gastric cancer tissues compared to adjacent non-cancerous tissues. This increased expression of YTHDF3 was found to be closely associated with the incidence of lymph node metastasis and the progression to more advanced TNM stages in patients.In vitroexperiments demonstrated that YTHDF3 is crucial in promoting the aggressive characteristics of gastric cancer cells by enhancing their ability to proliferate, migrate, and invade, while simultaneously inhibiting apoptosis. The role of YTHDF3 in the progression of gastric cancer was further confirmed by nude mouse subcutaneous tumor model, which showed slowed tumor growth upon YTHDF3 knockdown. This study further confirms through a series of experiments including Co-IP, Co-IF, Western blot, and rescue studies that YTHDF3 promotes the progression of gastric cancer by targeting NEK7 to regulate the Wnt/β-catenin signaling pathway. These pivotal findings highlight the YTHDF3/NEK7/Wnt/β-catenin axis as a promising and accessible therapeutic target for developing new treatments aimed at enhancing the outcomes for gastric cancer patients.
Decoy-seq unlocks scalable genetic screening for regulatory small noncoding RNAs
Authors: Choi Benedict , Sobti Sushil , Soto Larisa M. , Charbonneau Trey , Sababi Aiden , Navickas Albertas , Najafabadi Hamed S. , Goodarzi Hani
Published: January 2025

Small noncoding RNAs (smRNAs) play critical roles in regulating various cellular processes, including development, stress response, and disease pathogenesis. However, functional characterization of smRNAs remains limited by the scale and simplicity of phenotypic readouts. Recently, single-cell perturbation screening methods, which link CRISPR-mediated genetic perturbations to rich transcriptomic profiling, have emerged as foundational and scalable approaches for understanding gene functions, mapping regulatory networks, and revealing genetic interactions. However, a comparable approach for probing the regulatory consequences of smRNA perturbations is lacking. Here, we present Decoy-seq as an extension of this approach for high-content, single-cell perturbation screening of smRNAs. This method leverages U6-driven tough decoys (TuD), which form stable duplexes with their target smRNAs, for inhibition in the cell. Lentiviral-encoded TuDs are compatible with conventional single-cell RNA-sequencing (scRNA-seq) technologies, allowing joint identification of the smRNA perturbation in each cell and its associated transcriptomic profile. We applied Decoy-seq to 336 microRNAs (miRNAs) and 196 tRNA-derived fragments (tRFs) in a human breast cancer cell line, demonstrating its ability to uncover complex regulatory pathways and novel functions of these smRNAs. Notably, we show that tRFs influence mRNA polyadenylation and regulate key cancer-associated processes, such as cell cycle progression and proliferation. Therefore, Decoy-seq provides a powerful framework for exploring the functional roles of smRNAs in normal physiology and disease, and holds promise for accelerating future discoveries.
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

The 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

With 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.
Differential expression of transposable elements and upregulation of nucleic acid sensing pathways in pterygium
Authors: Demkowicz Patrick C , Hammes Emma , Theotoka Despoina , Chow Jessica , Bakhoum Mathieu F
Published: January 2025

Purpose: The mechanisms that lead to pterygium pathogenesis are poorly understood. Ultraviolet (UV) exposure is a leading environmental risk factor. We propose that UV triggers the de-repression of transposable elements (TEs), including endogenous retroviruses (ERVs), and subsequently activate double-stranded RNA and DNA sensors such as RIG-I and cGAS. Methods: In the present study, we analyzed publicly available RNA sequencing data from pterygium and healthy conjunctiva specimens. We used Ingenuity Pathway Analysis (IPA) to examine the relative expression of nucleic acid sensing pathways and related processes. We also used Telescope to identify TEs. We then repeated this analysis using RNA collected from cultured human conjunctival fibroblasts exposed over multiple days to a range of UV intensities. Results: We found that pathways involved in cellular stress, nucleic acid sensing, and innate immune signaling were upregulated in both cell lines exposed to increased amounts of UV energy as well as pterygium. We also observed differential expression of TEs. Conclusions: Taken together, our findings suggest a mechanistic link between environmental factors and pterygium. Understanding the molecular pathways activated by UV exposure may aid in developing therapeutic strategies.
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

Oncogene 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

Asian 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

Backgrounds

Ginkgo 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.

Objectives

The 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.

Methods

In 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.

Results

The 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.

Conclusion

Through 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

Selector 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

Endothelial 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

Ecological 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.
Decoding the immune response in leptomeningeal disease through single-cell sequencing of cerebrospinal fluid
Authors: Nieto Paula , Klinsing Svenja , Caratu Ginevra , Dettki Mareike , Marchese Domenica , Weber Katharina J , Morabito Samuel , Lorden Patricia , Ruano Irene , Imkeller Katharina , Velasco M. Angels , Vidal Silvia , Melero Juan L , Euskirchen Philipp , Czabanka Marcus , Plate Karl H , Harter Patrick N , Pascual-Reguant Anna , Steinbach Joachim P , Heyn Holger , Zeiner Pia S , Nieto Juan C
Published: January 2025

Assessing anti-tumor immune responses and immune microenvironments in central nervous system (CNS) neoplasms, such as brain tumors and leptomeningeal disease (LMD), provides prognostic insights and predictive biomarkers. Liquid biopsy of the cerebrospinal fluid (CSF) represents a promising minimally-invasive approach, but its ability to reflect immune responses against tumors remains unclear. Here, we used single-cell sequencing of CSF cells and spatial transcriptomics of CNS lesions to compare and contrast LMD patients with CNS lymphoma (CNSL), glioblastoma (GB) and brain metastases (BrM), to neuroinflammatory CNS disorders. We identified disease-specific CSF environments, reflecting parenchymal tumor microenvironment features. CNSL showed robust T cell responses, while BrM and GB were dominated by both blood-derived and tissue-resident myeloid cells. Longitudinal CSF sampling unveiled mechanisms of disease progression and therapy resistance, highlighting the potential of CSF liquid biopsies for uncovering disease biology, discovering cellular biomarkers and developing personalized therapies for CNS neoplasms.
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

Symmetry 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

Obesity 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

Motivation

Because 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.

Methods

Our 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.

Results

Our 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 Material

Software:https://github.com/rust-seq/simd-minimizers

Funding

Ragnar 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

The 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

Neuroethologists 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.
A PIF- and GUN1-regulated switch in cell axis growth drives cotyledon expansion through tissue-specific cell expansion and division
Authors: Veciana Nil , Martín Guiomar , Monte Elena
Published: January 2025

Despite its crucial role during seedling deetiolation, cotyledon expansion has been largely overlooked, with hypocotyl elongation favored as the primary phenotypic readout in light signaling research. Here, we investigate how cotyledon expansion is regulated during seedling establishment, and reveal that light-induced cotyledon expansion involves a rapid switch in growth direction - from longitudinal in darkness to transversal upon initial light exposure. Using PIFq- and phyA/phyB-deficient Arabidopsis mutants, we demonstrate that this switch is repressed by PIFs in the dark and promoted by phytochromes under red light. Notably, expansion is antagonistically regulated in the light by GUN1-mediated plastid retrograde signaling. Cotyledon expansion involves rapid epidermis cell expansion, transitioning from rectangular in darkness to characteristic lobed cells in light. Importantly, our findings show that mesophyll extension is driven not only by cell enlargement but also by palisade cell division, consistent with an enrichment of cell cycle-related genes that are antagonistically regulated by the PIF/phy system and retrograde signaling in the cotyledon. Finally, using mutant lines expressing PIF1 and phyB specifically in the epidermis, we establish that epidermal expansion can drive palisade cell growth, while mesophyll cell division is predominantly regulated by light at the tissue-specific level. This study provides a novel framework for investigating cotyledon expansion during seedling deetiolation, incorporating tissue-level regulation. We propose that cotyledons serve as an excellent model for studying morphogenesis and organ geometry, which in plants is governed by directional cell growth.

SIGNIFICANT STATEMENT

Despite their critical role in the successful establishment of green photoautotrophic organisms, the mechanisms governing cotyledon expansion during seedling deetiolation remain largely unknown. Our study reveals that the phy/PIF system drives a light-induced shift in the cotyledon growth axis to promote cotyledon growth through tissue-specific cell expansion and division, while GUN1-mediated plastid signals counteract this process when chloroplast biogenesis is impaired.
Fluorescence Lifetime Imaging Microscopy (FLIM) visualizes internalization and biological impact of nanoplastics in live intestinal organoids
Authors: Okkelman Irina A. , Zhou Hang , Borisov Sergey M. , Debruyne Angela C. , Lefebvre Austin E. Y. T. , Zoccoler Marcelo Leomil , Chen Linglong , Devriendt Bert , Dmitriev Ruslan I.
Published: January 2025

The increasing micro- and nanoplastic (MNP) pollution poses significant risks to human and animal health, yet the mechanisms of their accumulation and effects on absorptive tissues such as the gastrointestinal tract remain poorly understood. Addressing these knowledge gaps requires tractable models coupled to dynamic live cell imaging methods, to enable multi-parameter analysis at single cell resolution. Here we report a new method combining adult stem cell-derived small intestinal organoid cultures with multi-parameter live Fluorescence Lifetime Imaging Microscopy (FLIM) to study MNP interactions with gut epithelium. To facilitate this, we optimized live imaging of porcine and mouse small intestinal organoids with an ‘apical-out’ topology. Subsequently, we produced a set of pristine MNPs based on PMMA and PS (<200 nm, doped with deep-red fluorescent dye) exhibiting different surface charges, and evaluated their interaction with organoids displaying controlled epithelial polarity. We found that nanoparticles differently interacted with apical and basal membranes of the organoids and even showed a species-specific pattern of cellular uptake. Using a phasor-FLIM approach, we demonstrate better sensitivity of FLIM over conventional intensity-based microscopy. The ‘fluorescence lifetime barcoding’ enabled distinguishing different types of MNP and their interaction sites within organoids. Finally, we studied short (1 day)- and long (3 days)-term exposure effects of PMMA and PS-based MNPs on mitochondrial function, total energy budget and epithelial inflammation and found that even pristine MNPs could disrupt chemokine production and mitochondrial membrane potential in intestinal epithelial cells. The presented FLIM approach will advance the study of MNP toxicity, their biological impacts on gastrointestinal tissue and help tracing other types of fluorescent nanoparticles in live organoid and 3Dex vivosystems.
STOCHASTIC MODELING OF HEMATOPOIETIC STEM CELL DYNAMICS
Authors: Alfaro-Quinde Carlos , Krstanovic Katerina E. , Vásquez Paula A. , Kathrein Katie L.
Published: January 2025

The study of hematopoietic stem cell (HSCs) maintenance and differentiation to supply the hematopoietic system presents unique challenges, given the complex regulation of the process and the difficulty in observing cellular interactions in the stem cell niche. Quantitative methods and tools have emerged as valuable mechanisms to address this issue; however, the stochasticity of HSCs presents significant challenges for mathematical modeling, especially when bridging the gap between theoretical models and experimental validation. In this work, we have built a flexible and user-friendly stochastic dynamical and spatial model for long-term HSCs (LT-HSCs) and short-term HSCs (ST-HSCs) that captures experimentally observed cellular variability and heterogeneity. Our model implements the behavior of LT-HSCs and ST-HSCs and predicts their homeostatic dynamics. Furthermore, our model can be modified to explore various biological scenarios, such as stress-induced perturbations mediated by apoptosis, and successfully implement these conditions. Finally, the model incorporates spatial dynamics, simulating cell behavior in a 2D environment by combining Brownian motion with spatially graded parameters.

*Summary Statement

This study addresses the challenge of characterizing hematopoietic stem cell (HSC) dynamics by developing a flexible, user-friendly stochastic spatial model of long-term and short-term HSCs. The model captures observed cellular variability and heterogeneity, predicts homeostatic dynamics, can be adapted to simulate stress-induced perturbations like apoptosis, and incorporates a spatial component to analyze HSC movement within a bone marrow niche.
Bacteriophage-driven DNA inversions shape bacterial functionality and long-term co-existence inBacteroides fragilis
Authors: Carasso Shaqed , Keshet-David Roni , Zhang Jia , Hajjo Haitham , Kadosh-Kariti Dana , Gefen Tal , Geva-Zatorsky Naama
Published: January 2025

Bacterial genomic DNA inversions, which govern molecular phase-variations, provide the bacteria with functional plasticity and phenotypic diversity. These targeted rearrangements enable bacteria to respond to environmental challenges, such as bacteriophage predation, evading immune detection or gut colonization.

This study investigated the short- and long-term effects of the lytic phage Barc2635 on the functional plasticity ofBacteroides fragilis, a gut commensal. Germ-free mice were colonized withB. fragilisand exposed to Barc2635 to identify genomic alterations driving phenotypic changes.

Phage exposure triggered dynamic and prolonged bacterial responses, including significant shifts in phase-variable regions (PVRs), particularly in promoter orientations of polysaccharide biosynthesis loci. These shifts coincided with increased entropy in PVR inversion ratios, reflecting heightened genomic variability. In contrast,B. fragilisin control mice exhibited stable genomic configurations after gut adaptation. The phase-variable Type 1 restriction-modification system, which affects broad gene expression patterns, showed variability in both groups. However, phage-exposed bacteria displayed more restrained variability, suggesting phage-derived selection pressures. Our findings reveal thatB. fragilisemploys DNA inversions to adapt rapidly to phage exposure and colonization, leveraging genomic variability for resilience. This study emphasizes gut bacterial genomic and phenotypic plasticity upon exposure to the mammalian host and to bacteriophages.
Sequential oxidation of L-lysine by a non-heme iron hydroxylase
Authors: Reynolds Elizabeth S. , Smith Thomas G. , Damodaran Anoop R. , Bhagi-Damodaran Ambika
Published: January 2025

2-oxoglutarate-dependent non-heme iron hydroxylases offer a direct route to functionalizing C(sp3)–H bonds across a diverse range of substrates, making them prime candidates for chemoenzymatic synthetic strategies. We demonstrate the ability of a non-heme iron L-lysine dioxygenase to perform sequential oxidation and computationally explore structural elements that promote this reactivity.
Impact of the hole gas on optically detected magnetic resonance in
(Cd,Mn)Te
-based quantum wells
Authors: Łopion A. , Bogucki A. , Raczyński M. , Śnioch Z. , Połczyńska K. E. , Pacuski W. , Kazimierczuk T. , Golnik A. , Kossacki P.
Published: January 2025

Optically detected magnetic resonance (ODMR) is a useful technique for studying interactions between local spins (magnetic ions) and the carrier gas. We present an ODMR study of a single (Cd,Mn)Te/(Cd,Mg)Te quantum wells (QWs) with the hole gas. We observe different characteristics of the ODMR signals obtained simultaneously using the optical signals of the neutral and positively charged exciton. From this, we infer the existence of local fluctuations of carrier gas density resulting in separate populations of Mn2+ ions. At the same time, the shape of the ODMR signal contains information about the temperature of the magnetic ions involved in the absorption of the microwaves. Studying it in detail provides even more information about the interactions with charge carriers. In the QW, two separate ensembles of ions are thermalized differently in the presence of carriers.

Published by the American Physical Society
2025
Electric dipole moments from the perspective of a scalar triplet and singlet extension of the MSSM: A study of neutrons, electrons, mercury, and b and c quarks
Authors: Li Qing-hua , Yang Jin-Lei , Yang Xiang , Feng Tai-Fu
Published: January 2025

In the framework of the minimal supersymmetric model extension with new scalar triplets and singlet (TNMSSM), we analyze the electric dipole moment (EDM) of neutrons (dn), electrons EDM(de), mercury EDM(dHg), and b quarks (db) and c quarks (dc) by considering the contributions from the one-loop diagrams, some two-loop diagrams, and the Weinberg operators. The effects of TNMSSM specific CP-violating sources χd, χt on dn, de, dHg, db, and dc are specialized; it is found that they have significant contributions to these EDMs, and the current upper bounds on dn impose strict constraints on χd, χt. The theoretical predictions on db, dc can reach about 10−22  e·cm and 10−23  e·cm respectively by taking the upper bounds on dn, de, and dHg into account, which have great potential to be observed in the future.

Published by the American Physical Society
2025
Monochromatic mass spectrum of primordial black holes
Authors: Kleban Matthew , Norton Cameron
Published: January 2025

During slow-roll inflation, nonperturbative transitions can produce bubbles of metastable vacuum. These bubbles expand exponentially during inflation to superhorizon size, and later collapse into black holes when the expansion of the Universe is decelerating. Estimating the rate for these transitions during a time-dependent slow-roll phase requires the development of new techniques. Our results show that in a broad class of models, the inflationary fine-tuning that gives rise to small density fluctuations causes these bubbles to appear only during a time interval that is short compared to the inflationary Hubble time. As a result, despite the fact that the final mass of the black hole is exponentially sensitive to the moment bubbles form during inflation, the resulting primordial black hole mass spectrum can be nearly monochromatic. If the transition occurs near the middle of inflation, the mass can fall in the “asteroid” range 1017–1022  g in which all known observations are compatible with black holes comprising 100% of dark matter.

Published by the American Physical Society
2025
Quantum and Classical Dynamics with Random Permutation Circuits
Authors: Bertini Bruno , Klobas Katja , Kos Pavel , Malz Daniel
Published: January 2025

Understanding thermalization in quantum many-body systems is among the most enduring problems in modern physics. A particularly interesting question concerns the role played by quantum mechanics in this process, i.e., whether thermalization in quantum many-body systems is fundamentally different from that in classical many-body systems and, if so, which of its features are genuinely quantum. Here, we study this question in minimally structured many-body systems that are only constrained to have local interactions, i.e., local random circuits. In particular, we introduce random permutation circuits (RPCs), which are circuits comprising gates that locally permute basis states, as a counterpart to random unitary circuits (RUCs), a standard toy model for generic quantum dynamics. RPCs represent a model for generic microscopic classical reversible dynamics but, interestingly, can be interpreted both as classical or as quantum dynamics. We show that, upon averaging over all circuit realizations, RPCs permit the analytical computation of several key quantities such as out-of-time-order correlators (OTOCs) and entanglement entropies. In the classical setting, we obtain similar exact results relating (quantum) purity to (classical) growth of mutual information and (quantum) OTOCs to (classical) decorrelators. We, thus, discover a series of exact relations, connecting quantities in RUC and (quantum or classical) RPCs. Our results indicate that, despite the fundamental differences between quantum and classical systems, their many-body dynamics exhibits remarkably similar behaviors.

Published by the American Physical Society
2025
Why do rural and urban users adopt phygital payments differently? A UTAUT3-based comparative study of mobile wallets and plastic money
Authors: Pal Abhimanyu , Rani Priyanka , Singh Upendra Pratap , Rani Radha , Kumar Ashish
Published: January 2025

Purpose

This paper aims to identify the factors affecting the adoption of plastic money and mobile wallets by comparing rural and urban perspectives. For this, the study uses a unified theory of acceptance and use of technology (UTAUT3) model with additional variables, perceived value and perceived risk, to predict use behavior.

Design/methodology/approach

This research incorporates two cross-sectional surveys, Study R, which includes 417 rural respondents and Study U, which includes 431 urban respondents, regarding plastic money and mobile wallet adoption. This paper used the Statistical Package for Social Science and partial least squares-structural equation modeling for data analysis.

Findings

Both studies showed that performance expectancy, social influence and hedonic motivation substantially influence behavioral intention and use behavior. In contrast, effort expectancy has an insignificant influence in rural (Study R) and urban (Study U). In addition, personal innovativeness and perceived value positively influence, whereas perceived risk negatively influences behavioral intention and use behavior in both studies. However, facilitating conditions had a positive effect in Study U, but it had a negative effect on behavioral intention and use behavior in Study R.

Practical implications

This research lays a practical foundation for governments, policymakers and marketers to encourage a phygital payment service that explicitly addresses the rural and urban context. In addition, the findings of this paper also help regulatory authorities develop effective strategies and campaigns to encourage the sustainable development of countries.

Originality/value

This paper attempts to address the gap in the prevailing literature by investigating the role of geographical differences in the technology adoption system, especially in emerging nations like India, where these studies are missing. The adoption differences between rural and urban areas, along with the insightful findings by the authors, help to highlight the unique aspects of the context. As one of the pioneering studies, this research tests the UTAUT3 model, incorporating two additional constructs, to provide a comprehensive framework for using plastic money and mobile wallets – valuable for both researchers and practitioners.