bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cells are necessary for development of PCOS reproductive symptoms in a letrozole-induced mouse model of PCOS
Authors: Ujagar Naveena , Velez Leandro M. , De Robles Gabriela , Nguyen Christy , Wiggins Kiara , Kim Joshua , Naidu Nandini , Angulo Julio Ayala , Kauffman Alexander S. , Thackray Varykina G. , Banaszewska Beata , Wysocka Ewa , Duleba Antoni , Seldin Marcus , Nicholas Dequina 
Published: January 2025

AbstractPolycystic ovary syndrome (PCOS) is a complex condition with clear genetic susceptibilities that impact the heterogeneous clinical presentation of symptoms and severity through unknown mechanisms. Chronic inflammation is linked to PCOS, but a clear cause-and-effect relationship has yet to be established. This study used an in depth systems immunology approach and a letrozole-induced PCOS mouse model to identify changes in inflammatory factors associated with PCOS symptoms. By analyzing immune cells and secreted cytokines from 22 different mouse strains, we identified TNF-β as a key T cell-derived cytokine associated with PCOS, regardless of genetic background. We confirmed elevated TNF-β transcripts in immune cells from women with PCOS. Importantly, we used a knockout of TCRα to show that functional T cells are a necessary component of driving PCOS features in letrozole-treated female mice. These findings implicate T cells and specifically TNF-β production in the development of PCOS impairments. T cells are therefore an attractive target for the future development of anti-inflammatory therapeutics to improve PCOS symptoms.TeaserTNF-β links T cell inflammation to reproductive dysfunction in PCOS, highlighting new therapeutic targets for this disorder.
Cryopreservation of JuvenileMytilus galloprovincialis: Safeguarding Mollusk Biodiversity and Aquaculture
Authors: Lago A. , Troncoso J. , Paredes E. 
Published: January 2025

AbstractMytilus galloprovincialisLamarck, 1819, is a globally significant aquaculture species, contributing 25% of fresh seafood landings and leading EU mussel production. In Spain, it accounted for 255,218 tonnes in 2022, around 60% of the global harvest. This study introduces groundbreaking cryopreservation, being the first to successfully cryopreserve the juvenile stage of a marine organism, the largest marine organism ever cryopreserved. By optimizing feeding strategies, equilibration times, and cryoprotectant concentrations, we extended our initial protocol for young larvae to include complex larval stages (72h–26 days post-fertilization) and juveniles (40–45 days, up to 1 mm). These protocols mark a significant step in biodiversity conservation, seedstock preservation, genetic line maintenance, and sustainability of overexploited mollusk populations.
Atomistic Simulation of Voltage Activation of a Truncated BK Channel
Authors: Jia Zhiguang , Chen Jianhan 
Published: January 2025

AbstractVoltage-dependence gating of ion channels underlies numerous physiological and pathophysiological processes, and disruption of normal voltage gating is the cause of many channelopathies. Here, long timescale atomistic simulations were performed to directly probe voltage-induced gating transitions of the big potassium (BK) channels, where the voltage sensor domain (VSD) movement has been suggested to be distinct from that of canonical Kv channels but remains poorly understood. Using a Core-MT construct without the gating ring, multiple voltage activation transitions were observed at 750 mV, allowing detailed analysis of the activated state of BK VSD and key mechanistic features. Even though the S4 helix remains the principal voltage sensor in BK, its vertical displacement is only ∼3 Å and accompanied by significant lateral movements. The nature of the predicted VSD movement is in strong agreement with recent Cryo-EM structural studies of mutant BK channels with constitutively activated VSD. Free energy analysis based on the predicted activation transition yielded a total gating charge of 0.44eper VSD, consistent with the experimental range of 0.48 – 0.65e. We further show that the ability of modest physical movements with a small total gating charge to drive effective voltage gating of BK can be attributed to large gradients in the local electric field as reshaped by the protein. Furthermore, the S4 movement is coupled to the pore opening through a non-canonical pathway that involves the tightly packed S4-S5-S6 interface. These distinct mechanistic features may be relevant to voltage gating of other ion channels where VSDs are not domain-swapped with respect to the pore-gate domain.Significance StatementThe big potassium (BK) channel is the only potassium channel that integrates intracellular calcium signaling with membrane depolarization. It is considered one of the most important channels in cardiovascular and neurological disorders. It has been known that voltage gating of BK channels has distinct features compared to the canonical voltage gating mechanism established through studies of voltage-gated potassium (Kv) channels. Yet, little is known about the molecular nature of voltage sensing and pore activation of BK channels at present. Our work reports the first successful direct simulation of voltage activation of the big potassium (BK) channel, revealing novel voltage sensing and sensor-pore coupling mechanisms that have largely eluded the community until now.
Golgi-associated nuclear import receptor importin-7 targets HPV from the Golgi to the nucleus to promote infection
Authors: Woo Tai-Ting , Takeo Yuka , Harwood Mara C. , Houck Ethan T. , DiMaio Daniel , Tsai Billy 
Published: January 2025

AbstractDuring human papillomavirus (HPV) entry, the virus exploits COPI-dependent retrograde transport to cross the trans-Golgi network and Golgi stacks before reaching the nucleus to cause infection. How HPV enters the nucleus after exiting the Golgi is unclear, although mitotic nuclear envelop breakdown (NEB) appears important. Here we show that importin-7 (IPO7), a nuclear pore import receptor, associates with the Golgi and promotes HPV infection. Upon IPO7 knockdown, HPV infection is inhibited and the virus accumulates in the Golgi but does not enter the nucleus, demonstrating that IPO7 promotes Golgi-to-nucleus transport of HPV. We further reveal that the C-terminus of HPV capsid protein L2, which is thought to contain overlapping nuclear localization and cell-penetrating peptide sequences, binds directly to IPO7 in a step that requires COPI-dependent virus trafficking. Together these data identify a role of an importin in HPV infection, raising the possibility that the canonical nuclear pore import machinery plays an unanticipated role in NEB-dependent nuclear entry.TeaserHPV, a cancer-causing human pathogen, exploits the Golgi-associated nuclear import receptor IPO7 for Golgi-to-nucleus trafficking to promote infection.
AR-V7 condensates drive androgen-independent transcription in castration resistant prostate cancer
Authors: Massah Shabnam , Pinette Nicholas , Foo Jane , Datta Sumanjit , Guo Maria , Bell Robert , Haegert Anne , Tekoglu Tahsin Emirhan , Terrado Mailyn , Volik Stanislav , Bihan Stephane Le , Bui Jennifer M. , Lack Nathan A. , Gleave Martin E. , Rhie Suhn K. , Collins Colin C. , Gsponer Jörg , Lallous Nada 
Published: January 2025

SummaryBiomolecular condensates organize cellular environments and regulate key processes such as transcription. We previously showed that full-length androgen receptor (AR-FL), a major oncogenic driver in prostate cancer (PCa), forms nuclear condensates upon androgen stimulation in androgen-sensitive PCa cells. Disrupting these condensates impairs AR-FL transcriptional activity, highlighting their functional importance. However, resistance to androgen deprivation therapy often leads to castration-resistant prostate cancer (CRPC), driven by constitutively active splice variants like AR variant 7 (AR-V7). The mechanisms underlying AR-V7’s role in CRPC remain unclear. In this study, we characterized the condensate-forming ability of AR-V7 and compared its phase behavior with AR-FL across a spectrum of PCa models andin vitroconditions. Our findings indicate that cellular context can influence AR-V7’s condensate-forming capacity. Unlike AR-FL, AR-V7 spontaneously forms condensates in the absence of androgen stimulation and functions independently of AR-FL in CRPC models. However, AR-V7 requires a higher concentration to form condensates, both in cellular contexts andin vitro. We further reveal that AR-V7 drives transcription via both condensate-dependent and condensate-independent mechanisms. Using an AR-V7 mutant incapable of forming condensates, while retaining nuclear localization and DNA-binding ability, we reveal that the condensate-dependent regime activates part of the oncogenic KRAS pathway in CRPC models. Genes under this condensate-dependent regime were found to harbor significantly higher numbers of AR-binding sites and exhibited boosted expression in response to AR-V7. These findings uncover a previously unrecognized role of AR-V7 condensate formation in driving oncogenic transcriptional programs and shed light on its unique contribution to CRPC progression.HighlightsAR-V7 condensates form independently of both androgens and AR-FL in CRPC models.AR-V7 mediates condensate-dependent and independent transcriptionCondensate-dependent transcription enables boosted expression of oncogenic KRAS genesCondensate-dependent genes exhibit an exponential increase in expression, with a higher number of AR binding sites potentially playing a key role in their reliance on condensate formation.Graphical Abstract
RETINA: Reconstruction-based Pre-Trained Enhanced TransUNet for Electron Microscopy Segmentation on the CEM500K Dataset
Authors: Xing Cheng , Xie Ronald , Bader Gary D. 
Published: January 2025

ABSTRACTElectron microscopy (EM) has revolutionized our understanding of cellular structures at the nanoscale. Accurate image segmentation is required for analyzing EM images. While manual segmentation is reliable, it is labor-intensive, incentivizing the development of automated segmentation methods. Although deep learning-based segmentation has shown promise, its accuracy to automatically segment cellular structures in EM data remains insufficient compared to expert manual results. Current approaches usually use either convolutional or transformer-based neural networks for image feature extraction. We developed the RETINA method, which combines pre-training on the large, unlabeled CEM500K EM image dataset with a hybrid neural-network model architecture that integrates both local (convolutional layer) and global (transformer layer) image processing to learn from manual image annotations. RETINA outperformed existing models on cellular structure segmentation on five public EM datasets. This improvement works toward automated cellular structure segmentation for the EM community. Data and code are available atZenodoandGitHub.
Tissue imprinting defines functional mosaic of dermal macrophages
Authors: Lohrmann Florens , Sankowski Roman , Schwer Stephan , Neuber Jana , Vlachou Evi P , Westermann Frederike , Troesch Emma , Kolter Julia , Kathrin Lösslein Anne , Das Mahapatra Kunal , Döring Clarissa-Laura , Ghanem Nisreen , Kohnert Eva , Heselich Aileen , Staszewski Ori , Monaco Gianni , Müller Antonia , Eyerich Kilian , Zeiser Robert , Prinz Marco , Becher Burkhard , Zaugg Judith , Kreutz Clemens , Sagar  , Henneke Philipp 
Published: January 2025

AbstractDermal macrophages (macs) protect the skin from invading pathogens. They are derived from embryonic as well as hematopoietic progenitors. However, the functional impact of their diverse origin and the control networks defining different subsets remain unclear. Here, using multidimensional analysis of dermal macs, we reveal that the absence of circulating monocytes in interferon regulatory factor 8 (Irf8) deficient mice delays mac renewal during the steady state. Yet, the functional mosaic of dermal macs remains largely intact, i.e., major dermal mac subsets develop independently of monocyte replenishment. Thus, the tissue microenvironment is sufficient to induce alternative differentiation pathways and functional specialization of resident cells. Mycobacterial skin infection induces a steep increase in mac density due to monocyte-derived macs which execute urgent antibacterial functions and differentiate into site-adapted mac subsets in wildtype but notIrf8-/-mice, while long-term resident macs are required to initiate a tissue repair program already in early stages of infection.In summary, we introduce a model, where an intricate network of specialized mac subsets develops to meet microanatomical needs and external cellular input is required only during immunological emergency situations.HighlightsIrf8-/--driven monocytopenia has negligible impact on homeostatic dermal macrophage diversity.Resident dermal macrophages have diverse specializations but remain flexible to adapt to challenges such as lacking monocyte influxBone marrow-derived macrophages differentiate into specialized resident cells, with microenvironmental cues overriding origin-dependent programming.In chronic bacterial infections, distinct specialized bone-marrow-derived macrophages mount the defense, while resident macrophages activate a tissue-modifying program from early on.
A single pathogen-secreted protein reprograms plants for drought resilience
Authors: Subieta Konrad , Weber Leonie , Lübbers Jan-Niclas , Wiesotzki Karin , Pierdzig Leon , Thurow Corinna , Schmitz Johanna , Lipka Ulrike , Heimel Kai , Schmitt Kerstin , Thürmer Andrea , Poehlein Anja , Daniel Rolf , de Vries Jan , Valerius Oliver , Braus Gerhard H. , Polle Andrea , Gatz Christiane , Teichmann Thomas , Lipka Volker 
Published: January 2025

AbstractClimate change-enforced drought stress conditions and diseases caused by pathogens often co-occur and represent one of the greatest challenges in plant science1–3. Wilt pathogens that colonize water-conducting plant tissues can aggravate the problem and affect a wide range of agricultural crops4,5. However, whilst fungal infections with the vascular pathogenVerticillium dahliaeare typically associated with wilt symptoms due to occlusion of xylem tissues, the relatedV. longisporuminducesde novoformation of tracheary elements6,7. This promotes not only its virulence but also enables elevated water storage capacity of the infected host plant and resilience against drought stress conditions6,7. Here, we identified a secretedVerticilliumprotein,TRANSDIFFERENTIATIONEFFECTOR (TRADE), which triggers cell identity switches of bundle sheath cells into tracheary elements. We show that TRADE interacts with the intracellular plant protein VARICOSE (VCS), a conserved component of the mRNA turnover machinery and ortholog of the metazoan protein ENHANCER OF DECAPPING 4 (EDC4/HEDLS/Ge-1)8. The TRADE-VCS interaction induces SUCROSE NON-FERMENTING 1 (SNF1)-related protein kinase (SRK)-dependent phosphorylation and thus dysfunction of VCS. This affects the abundance of mRNAs encoding master regulators of xylem differentiation and demonstrates how a single pathogen effector protein triggers complex tissue-specific developmental reprogramming and thus promotes abiotic stress resilience.
Overcoming pride via the dorsal ACC underlies acceptance of unfair offers
Authors: Numano Shotaro , Frith Chris , Haruno Masahiko 
Published: January 2025

AbstractBargaining is a fundamental social behavior in which individuals often accept unfair offers. Traditional behavioral models, based solely on choice data, typically interpret this acceptance as simple reward-maximization. However, the suppression of emotions such as inequity aversion or pride may also play a critical role in this decision. Incorporating response time alongside choice data provides a means to quantify participants’ internal conflict in suppressing these emotions and deciding to accept unfair offers. In this study, we conducted functional magnetic resonance imaging (fMRI) of the ultimatum game, where participants decided within 10 seconds whether to accept or reject monetary distribution offers from a proposer. Using the drift diffusion model (DDM), we quantified decision-making dynamics based on both choice and response time. Participants who suppressed disadvantageous inequity (DI)-driven rejection (reflected by a lower DDM weight for DI) exhibited heightened dorsal anterior cingulate cortex (dACC) activity in response to DI. Functional connectivity analysis revealed a negative correlation between the dACC and the ventrolateral prefrontal cortex (vlPFC) when DI was large, which encoded both the rejection rates, and the response times associated with accepting DI offers. Furthermore, vlPFC activity was significantly correlated with amygdala activity during high DI conditions, specifically encoding response time for accepting DI offers but not rejection rates. Importantly, these findings could not be captured using standard value-based models that rely solely on choice data. Our results underscore the dACC’s critical role in mediating the suppression of emotional responses to DI, enabling the acceptance of unfair offers in a dynamic bargaining process.
Biomimetic hydrogel platform reveals active force transduction from retinal pigment epithelium to photoreceptors
Authors: Korpela Sanna , Kauppila Maija , Karema-Jokinen Viivi , Sukki Lassi , Kallio Pasi , Skottman Heli , Nymark Soile , Ihalainen Teemu O. 
Published: January 2025

AbstractRetinal pigment epithelium (RPE) is an epithelial monolayer located at the back of the eye underneath the neural retina. RPE and retina interact closely, with RPE performing multiple tasks to ensure proper retinal physiology and forming a tight, interlocked structure with photoreceptor outer segments (POS). Essential for retinal welfare, RPE enables the daily renewal of POS by phagocytosing their aged tips. Current RPEin vitrocell culture systems lack the contact between RPE and retina, possibly limiting not only RPE maturation but also hindering the studies addressing the RPE-retina interactions. We constructed a retina-mimicking structure from a soft polyacrylamide hydrogel with Matrigel coating and introduced it to RPE cells’ apical side during culturing to model the RPE-retina interfacein vitro. RPE cells adhered to the hydrogels during culture, enabling further studies of the biophysical properties of the RPE-hydrogel interface with methods utilizing rheology and traction force microscopy. During phagocytosis, RPE cells generated considerable traction forces that were followed using a hydrogel coated with POS particles. Disruption of RPE’s actin cytoskeleton with Cytochalasin D significantly reduced the force generation. These results support the view of RPE as a mechanically active partner for retina. In addition, our retina-mimicking structure offers a tool for further biophysical modeling of the RPE-retina interface.
occumb: An R package for site occupancy modeling of eDNA metabarcoding data
Authors: Fukaya Keiichi , Hasebe Yuta 
Published: January 2025

AbstractEnvironmental DNA (eDNA) metabarcoding has become an increasingly popular method for the rapid assessment of species distribution and diversity. However, the detection of DNA sequences of species in eDNA metabarcoding is not flawless; thus, accounting for potential false negatives (nondetection of DNA sequences of existing species) is crucial for the effective implementation of eDNA-based monitoring and research. This study introduces the occumb R package, which was developed to facilitate the easy and flexible application of community site occupancy modeling for eDNA metabarcoding that accounts for the imperfect detection of DNA sequences of species. The package provides functions for specifying models using the formula syntax, Bayesian model fitting using Markov chain Monte Carlo (MCMC), posterior inferences, and model assessments and exploring optimal study settings based on the fitted model. A case study of eDNA metabarcoding on riverine aquatic insects is illustrated using the occumb package, emphasizing the importance of ensuring biological replicates in achieving reliable species detection in eDNA metabarcoding. By making complex community site occupancy models easily accessible to users, we hope that the development of the occumb package will promote eDNA metabarcoding applications for the accurate assessment of species distribution and diversity.
Evidence for multiple independent expansions of Fox gene families within flatworms
Authors: Gąsiorowski Ludwik 
Published: January 2025

AbstractExpansion and losses of gene families are important drivers of molecular evolution. A recent survey of Fox genes in flatworms revealed that this superfamily of multifunctional transcription factors, present in all animals, underwent extensive losses and expansions during platyhelminth evolution. In this paper, I analyzed Fox gene complement in four additional species of platyhelminths, that represent early-branching lineages in the flatworm phylogeny: catenulids (Stenostomum brevipharyngiumandStenostomum leucops) and macrostomorphs (Macrostomum hystrixandMacrostomum cliftonense). Phylogenetic analysis of Fox genes from this expanded set of species provided evidence for multiple independent expansions of Fox gene families within flatworms. Notably,FoxG, a panbilaterian brain-patterning gene, appears to be the least susceptible to duplication, whileFoxJ1, a conserved ciliogenesis factor, has undergone extensive expansion in various flatworm lineages. Analysis of the single-cell atlas of S.brevipharyngium, combined with RNAin situhybridization, elucidated the tissue-specific expression of the selected Fox genes:FoxGis expressed in the brain, three of the Fox genes (FoxN2/3-2, FoxO4andFoxP1) are expressed in the pharyngeal cells of likely glandular function, while one of theFoxQDparalogs is specifically expressed in the protonephridium. Overall, the evolution of Fox genes in flatworms appears to be characterized by an early contraction of the gene complement, followed by lineage-specific expansions that have enabled the co-option of newly evolved paralogs into novel physiological and developmental functions.Statements and DeclarationsThe author has no competing interests to declare that are relevant to the content of this article. The research was funded by the Alexander von Humboldt Foundation (The Humboldt Research Fellowship for Postdoctoral Researchers) and The Polish National Agency for Academic Exchange (Polish Returns NAWA grant no. BPN/PPO/2023/1/00002).