bluuebunny/crossref_metadata_2025_split huggingface dataset:
GsMTx-4 Reduces Mechanosensitivity in a Model of Schwannomatosis-related Pain
Authors: Gutierrez Carson , Rubright Randy , Ostrow Kimberly Laskie 
Published: February 2025

AbstractPatients with schwannomatosis (SWN) develop multiple tumors along major peripheral nerves, with most experiencing significant pain, though each patient’s symptoms are unique. Neuropathic, nociceptive, and inflammatory pain types have been reported, but many patients describe severe pain when a schwannoma is palpated or even lightly touched. Currently, the only effective treatment for pain relief is surgical removal. We are investigating the root causes of tumor-induced pain. In some cases, tumor growth increases pressure on nearby nerves, resulting in pain. Additionally, schwannoma cells in culture secrete proinflammatory cytokines into the surrounding medium. This conditioned medium (CM) sensitizes sensory neurons to painful stimuli both in vitro and in vivo. When injected into the glabrous skin of a mouse hindpaw, CM from painful schwannomas increases neuron sensitivity to light touch, as demonstrated by a fourfold reduction in paw withdrawal threshold (measured using the Von Frey assay) one hour post-injection (p = 0.006), with effects persisting for 24 hours (p = 0.002).We hypothesize that this increase in sensitivity is linked to mechanosensitive ion channels (MSCs), which detect pressure and stretch. These channels can be blocked by the peptide GsMTx-4. This peptide penetrates deeper into cell membranes under mechanical pressure to block MSCs from opening without affecting other ion channels. When co-injected with CM into the mouse hindpaw, 10 µM GsMTx-4 prevents heightened sensitivity to light touch. Moreover, GsMTx-4 can reverse hyperalgesia, restoring withdrawal thresholds to baseline levels. Thus, local injection of GsMTx-4 near painful tumors presents a promising, minimally invasive therapeutic approach for SWN patients.SignificancePain is a confounding comorbidity in the multiple tumor syndrome schwannomatosis. Patients harbor benign peripheral nerve sheath tumors that rarely become malignant or cause neurological deficits. Yet, patients undergo numerous surgeries for the removal of painful tumors. A non-invasive treatment for tumor-related pain is in dire need. We are examining the small peptide GsMTx-4, a blocker of mechanosensitive ion channels, as a potential therapy for painful tumors in the context of schwannomatosis.
Viral infection impacts volatile organic compound production in the coccolithophoreGephyrocapsa huxleyi
Authors: Buchholz Holger H. , Mojica Kristina D.A. , Comstock Jacqueline , Collart Lindsay , Giovannoni Stephen J. , Halsey Kimberly H. 
Published: February 2025

AbstractVolatile Organic Compounds (VOCs) are a diverse collection of molecules critical to cell metabolism, food web interactions, and atmospheric chemistry. The eukaryotic coccolithophoreGephyrocapsa huxleyi, an abundant coastal eukaryotic phytoplankter, forms massive blooms in coastal upwelling regions, which are often terminated by viruses (EhVs).G. huxleyiproduces organosulfur VOCs such as dimethyl sulfide (DMS) and halogenated metabolites that play key roles in atmospheric chemistry. Here we resolved the role of lytic viral infection by EhV207 on VOC production of the model strainG. huxleyiCCMP374. Our analysis identified 79 VOCs significantly impacted by viral infection, particularly during cell lysis, with sulfur containing VOCs like DMS dominating the profiles. Viral lysis results in a nearly six-fold increase in VOC production and generated a previously unrecognized range of VOCs, including 15 sulfur, 22 nitrogen, 2 phosphorus, 19 oxygen and 17 halogen-containing compounds. These findings reveal that viral infection ofG. huxleyireleases VOCs which are much more diverse than previously recognized. We further show that EhV207 primarily accelerates existing metabolic processes inG. huxleyiand facilitates the release of pre-existing intracellular VOCs rather than inducing novel biochemical pathways. This wide range of VOCs may be produced on a massive scale during coccolithophore bloom-and-bust cycles, with important impacts on coastal biogeochemistry and surface ocean/atmosphere interactions.
Aseptic, semi-sealed cranial chamber implants for chronic multi-channel neurochemical and electrophysiological neural recording in nonhuman primates
Authors: Choi Jiwon , Amjad Usamma , Murray Raymond , Shrivastav Ritesh , Teichert Tobias , Goodell Baldwin , Schaeffer David J. , Oluoch Julia K. , Schwerdt Helen N. 
Published: February 2025

AbstractWe developed an implantable neural interface for monitoring both chemical and electrical forms of brain activity in monkeys that maintains aseptic properties for year-long periods while leveraging the modular functions (e.g., sensor moveability) provided by a chamber system. Invasive electrophysiological recordings, especially in subcortical structures from nonhuman primates usually involves implanting electrodes into the brain through a skull-mounted chamber. These electrodes may be attached temporarily for several hours of recording, or permanently. Permanent attachments are favorable to allow for sealing the chamber completely from externally originating pathogenic species that can infiltrate and compromise the health of the animal. A sealed chamber also reduces the need for frequent chamber cleaning required to minimize the accumulation of pathogenic organisms. However, neurochemical measurements require specialized electrodes with extremely fragile carbon fiber tips and are not compatible with recently developed sealed chamber systems. Here, we leveraged osseointegrating materials and hermetic sealing strategies to enable both neurochemical and electrical neural activity measurements from a sealed chamber with an aspirating port for culturing chamber fluid to ensure an aseptic environment. The system was shown to provide successful recordings of neural activity in two monkeys while maintaining negative bacteria culture results for over a year post-implant.
Temporal dose inversion properties of adaptive biomolecular circuits
Authors: Nakamura Eiji , Blanchini Franco , Giordano Giulia , Hoffmann Alexander , Franco Elisa 
Published: February 2025

SUMMARYCells have the capacity to encode and decode information in the temporal features of molecular signals. Many pathways, for example, generate either sustained or pulsatile responses depending on the context, and such diverse temporal behaviors have a profound impact on cell fate. Here we focus on how molecular pathways can convert the temporal features of dynamic signals, in particular how they can convert transient signals into persistent downstream events and vice versa. We describe this type of behavior as temporal dose inversion, and we demonstrate that it can be achieved through adaptive molecular circuits. We consider motifs known as incoherent feedforward loop (IFFL) and negative feedback loop (NFL), and identify parametric conditions that enable temporal dose inversion. We next consider more complex versions of these circuits that could be realized using enzymatic signaling and gene regulatory networks, finding that both circuits can exhibit temporal dose inversion. Finally, we consider a generalized IFFL topology, and we find that both the time delay in the inhibition pathway and the relative signal intensities of the activation and inhibition signals are key determinants for temporal dose inversion. Our investigation expands the potential use of adaptive circuits as signal processing units and contributes to our understanding of the role of adaptive circuits in nature.
Proximity determines donor candidacy during DNA double-stranded break homology directed repair
Authors: Yeh Charles D , van de Venn Lilly , Kreutzer Susanne , Zheng Xinhe , Cantos Naomi C. , Schröder Markus , Hofmann Robin , Gerbaldo Felix E. , Clemens Alexandra , Wienert Beeke , Richardson Christopher D. , Kontarakis Zacharias , Corn Jacob E. 
Published: February 2025

AbstractDNA double-stranded breaks (DSBs) are especially toxic events that can be reversed by homology-directed repair (HDR), wherein information is copied from an intact template molecule. RAD51 mediates initial DSB/template pairing during homology search. A major challenge in understanding homology search in cells is the lack of tools to monitor this process. We developedRAD51proximityidentificationsequencing (RaPID-seq), a sensitive method that marks all candidate templates searched by RAD51. We find that HDR is hierarchical, such that DSB proximity determines template candidacy and subsequent recombination is unlocked by DSB/template homology. Sequences that lie outside the proximal window are not efficiently searched, even if identical in sequence. Our data reveal the invisible process of homology search and shed new light on fundamental mechanisms underlying genome editing.
Stable Actin As Synaptic Tag
Authors: Thomas Mitha , Bogaciu Cristian-Alexandru , Rizzoli Silvio O. , Fauth Michael 
Published: February 2025

AbstractAccording to the tagging and capture hypothesis, long-lasting long-term potentiation (LTP) requires protein synthesis and a synaptic tag, which is a synapse specific memory of the synapse with a so far unclear molecular or biophysical identity. Here we use an interdisciplinary approach to explore the hypothesis that interaction between the dynamics of actin and the spine geometry can provide such a memory. Using a mathematical model, we demonstrate that this implementation of the tag requires an increase in the stable, cross-linked pool of actin filaments, and is not possible without this stable pool. Using FRAP experiments, we show that such an increase in stable actin can indeed be observed after cLTP in vitro. Thus, the interaction between actin dynamics and spine geometry could indeed serve as a synaptic tag for LTP.
Exonuclease ISG20 inhibits human cytomegalovirus replication by inducing an innate immune defense signature
Authors: Hehl Matthias , Scherer Myriam , Raubuch Eva-Maria , Ploil Claudia , Rummel Teresa , Kirchner Philipp , Kottmann Nina , Reichel Anna , Kuderna Anna Katharina , König Anne-Charlotte , Friedel Caroline C. , Erhard Florian , Stamminger Thomas 
Published: February 2025

AbstractISG20 is an interferon-regulated protein that exhibits RNase activity thereby inhibiting the replication of a broad spectrum of RNA viruses. By single cell RNA sequencing, we identified ISG20 as an antiviral factor for human cytomegalovirus (HCMV) as it was upregulated in a population of HCMV-resistant cells. In accordance with an antiviral role on herpesviruses, overexpression of ISG20 in primary human fibroblasts led to reduced HCMV and HSV-1 replication, while knockdown of ISG20 enhanced virus growth. In Western blot kinetics, we observed that inhibition of HCMV replication by ISG20 occurs at the early stage of infection which correlated with reduced amounts of viral early and late transcripts. However, neither the half-life of viral and cellular RNAs nor of viral DNA was decreased in ISG20-expressing cells, indicating that ISG20 does not exert its antiviral effect via a degradation of RNAs or DNA. Instead, RNA-seq analysis revealed an innate immune defense signature upon ISG20 expression that comprised the upregulation of a distinct set of interferon stimulated genes (ISGs), zinc finger proteins (ZNFs) and of transposable elements (TEs). Our data indicate that this gene signature augments both IFN production and response of the host cell. Consistently, the JAK-STAT inhibitor ruxolitinib rescued HCMV gene expression in ISG20-expressing cells. We conclude that ISG20 induces a so far unprecedented immune defense signature that serves to amplify the IFN-mediated host cell defense thus explaining its broad antiviral activity.
Loss of Cathepsin K impairs collagen biogenesis and enhances actin polymerization in trabecular meshwork
Authors: Soundararajan Avinash , Jaysankar Krishna , Doud Emma , Pasteurin Rodahina Philihina , Surma Michelle , Pattabiraman Padmanabhan P 
Published: February 2025

AbstractTrabecular meshwork (TM) dysfunction and extracellular matrix (ECM) dysregulation contribute to increased intraocular pressure (IOP) in primary open-angle glaucoma (POAG). Earlier, we provide a proof-of-concept study identifying the regulation and the role of Cathepsin K (CTSK), a potent collagenase, in ECM homeostasis, actin bundling, and IOP regulation. Better understanding of the loss of CTSK function in TM remains unclear. Using siRNA-mediated knockdown of CTSK (siCTSK) in human TM cells, this study investigated the role of CTSK in actin and ECM homeostasis using an unbiased proteomics approach. Loss of CTSK significantly disrupted collagen biogenesis and ECM homeostasis. CTSK depletion also increased intracellular calcium levels, with proteomics data suggesting possible involvement of calcium-regulatory proteins. Additionally, PRKD1 activation enhanced actin polymerization through the LIMK1/SSH1/cofilin pathway, promoting focal adhesion maturation. Despite increased apoptotic markers (CASP3, CASP7, TRADD, PPM1F), caspase 3/7 activation was not induced, suggesting apoptosis-independent cellular remodeling. Notably, RhoQ and myosin motor proteins were significantly downregulated, indicating altered mechanotransduction in TM cells. These findings highlight the role of CTSK in maintaining ECM homeostasis, calcium signaling, and cytoskeletal regulation in TM. Its depletion induces actin polymerization, which may influence aqueous humor outflow. Targeting CTSK-related pathways may provide novel therapeutic strategies for regulating IOP and preventing glaucoma progression.
Enhancing Reproducibility Through Bioimage Analysis: The Significance of Effect Sizes and Controls
Authors: Barry David J. , Marcotti Stefania , Gerontogianni Lina , Kelly Gavin 
Published: February 2025

AbstractBioimage analysis is a powerful tool for investigating complex biological processes, but its robustness depends on both technical precision and rigorous experimental design. In particular, the use of appropriate controls is critical for drawing meaningful biological conclusions. However, controls are often inadequately applied or overlooked in favour of achieving statistical significance, frequently obtained through the misuse or misinterpretation of statistical tests. In this study, we reanalyse a publicly available image dataset to highlight the crucial role of controls in interpreting experimental outcomes. Our findings underscore the importance of focusing on effect sizes and biological relevance over arbitrary statistical thresholds. We also discuss the diminishing returns of increased data collection once statistical stability has been achieved, advocating for more efficient experimental designs. By refining control usage and emphasising effect sizes, this work aims to enhance the reproducibility and robustness of research findings. We provide open-access code to allow researchers to engage with the dataset, promoting better practices in experimental design and data interpretation.
Polycomb group proteins protect latent Kaposi sarcoma-associated herpesvirus from episome clearance and HUSH-dependent chromatin silencing
Authors: Weissmann Simon , Robitaille Alexis , Günther Thomas , Ziegler Marion , Grundhoff Adam 
Published: February 2025

AbstractKaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of a number of human neoplasms. KSHV causes lifelong chronic infections by establishing persistent reservoirs of latently infected cells in which the viral double-stranded DNA genome is present in the form of an extrachromosomal episome. Polycomb group protein (PcG) mediated gene repression is detected early after entry of the CpG-rich and epigenetically naïve viral DNA into the host nucleus. Here we show that the establishment and maintenance of KSHV latency is strongly influenced by Polycomb Repressive Complexes 1 and 2 (PRC1, and PRC2, respectively). Using a series of genetic deletion models, we dissect the functional interdependence of PRC1 and PRC2 on KSHV and identify KSHV episomes as a prime target for independent as well as collaborativede novoPRC recruitment. Loss of PRC function leads to a severely altered chromatin state on KSHV and we show that PRC mediated gene repression is not only preventing transcription of viral genomes but also protects KSHV episomes from detection by the human silencing hub (HUSH). Furthermore, we demonstrate that PRC complexes play an important role in ensuring episomal maintenance in dividing cells. Taken together, our results show that absence of PRC complexes creates a metastable state of KSHV latency and suggest early chromatinization as an integral step for KSHV latency establishment.
Mammalian oocytes receive maternal-effect RNAs from granulosa cells
Authors: Doherty Caroline A. , Tijjani Abdulfatai , Munger Steven C. , Laird Diana J. 
Published: February 2025

SummaryIt is currently thought that growing mammalian oocytes receive only small molecules via gap junctions from surrounding support cells, the granulosa cells. From the study of chimeric preantral oocyte and granulosa cell reaggregations, we provide evidence that growing mouse oocytes receive mRNAs from granulosa cells. Among the >1,000 granulosa-transcribed RNAs we identified in the oocyte, those that contribute to proper oocyte maturation and early embryo development were highly enriched. Predicted motifs for two RNA-binding proteins that function in RNA trafficking, FMRP and TDP43, were abundant in the UTRs of the granulosa-derived transcripts. Immunostaining demonstrated that both FMRP and TDP43 co-localize with the actin-rich granulosa cell protrusions that span the zone pellucida and connect to the oocyte, suggesting their role in importing mRNAs. Our results offer the possibility that oocyte failure may not always reflect an intrinsic oocyte deficiency but could arise from insufficient supply of maternal transcripts by granulosa cells during oocyte growth.
Semi-automatic quantification of 3D Histone H3 phosphorylation signals during cell division inArabidopsisroot meristems
Authors: Kelemen Adrienn , Uyttewaal Magalie , Máthé Csaba , Andrey Philippe , Bouchez David , Pastuglia Martine 
Published: February 2025

SummaryPosttranslational modification of histones during the cell cycle is a major process controlling many aspects of cell division. Among the variety of histone modifications, mitotic phosphorylation of histone H3 at serine 10 (H3S10ph) plays a crucial role, particularly in proper chromosome segregation. Here we aimed at precisely quantifying this phosphorylation dynamics during mitosis in plant cells, in order to reveal molecular pathways involved in this process.We describe an analysis pipeline based on 3D image analysis that allows to semi-automatically quantify H3S10 phosphorylation in mitoticArabidopsisroot cells. We also developed a new method for the compensation of signal attenuation in Z, based on measurement of objects of interest themselves.We show that this new attenuation correction method allows significant gains in accuracy and statistical power. Using this pipeline, we were able to reveal small H3S10ph differences between cells treated with hesperadin, an inhibitor of an H3S10ph kinase, or betweenArabidopsismutants affected in PP2A phosphatase activity.This tool opens new avenues to explore such regulation pathway in plants, using the wealth of genetic material available inArabidopsis. It can also be applied to study other histone post-translational modifications, and more generally to any discrete 3D signals.
Does a board of directors enhance sustainable development? Evidence from emerging economies in Southeast Asia
Authors: Nguyen Linh-TX 
Published: February 2025

Purpose
This study empirically examines the relationship between board effectiveness and corporate sustainability performance through the lens of agency and stakeholder theories to determine whether a board of directors enhances sustainable development.

Design/methodology/approach
The author uses best practices from Institutional Shareholders Services (2016) to develop a firm-specific board index that integrates four key attributes, including board size, board independence, board leadership structure and the presence of an audit committee. The analysis uses fixed-effects regressions on a sample of 535 listed non-financial firms in emerging Southeast Asian markets.

Findings
The findings demonstrate that an effective board can enhance corporate sustainability performance. Among the four board attributes, the author finds that an optimal board size, a majority of independent directors and the establishment of an audit committee contribute to improved corporate sustainability performance. However, there is no impact of CEO duality on sustainable development.

Originality/value
The author contributes to the literature by proposing a comprehensive firm-specific board index to evaluate board effectiveness, clarifying the attributes of a well-functioning corporate board. Additionally, our research emphasizes the crucial role of a well-functioning board of directors in enhancing sustainable development, particularly in emerging Southeast Asian markets.
Cultural intermediation as a balancing act: exploring the role of communications professionals as cultural intermediaries in UK cancer charities
Authors: Malaussene Laura 
Published: February 2025

PurposeThis study examined the role of communications professionals as cultural intermediaries within the UK cancer charity sector. It aimed to reposition politics within cultural and economic spheres in order to explore how these forces collectively shape the strategies and practices of communications professionals.Design/methodology/approachA qualitative method was employed by conducting 20 in-depth, semi-structured interviews to gain a deeper understanding of the experiences, perspectives and insights of various communications professionals in UK cancer charities.FindingsThe results showed that cultural intermediation has become increasingly complex in a cancer charity sector affected by changes in government leadership, increased competition and budget cuts. This evolution in communications practices has had an impact on relations with government and on the politicisation of cultural intermediaries’ strategies. Further, the infusion of neoliberalism and commercialisation underlines the central role of cultural intermediaries in navigating market relations and acting as neoliberal subjects.Originality/valuePolitics has been analytically excluded to the detriment of culture and economics in the external forces shaping the work of communications professionals as cultural intermediaries. This study seeks to reposition politics alongside other spheres of life in the analysis of cultural intermediation by utilizing concepts such as political economy, cultural intermediation and neoliberal subjects. It specifically focuses on the cancer charity sector, which has received less scholarly attention in the literature on cultural intermediaries.