bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fixation shifts in a novel “no-report” binocular rivalry paradigm induce saccade-related perceptual switches
Authors: Kingir Ege , Segawa Ryo , Hesse Janis K. , Kagan Igor , Wilke Melanie 
Published: February 2025

AbstractNo-report paradigms help to avoid report-related confounds in conscious perception studies. A novel no-report binocular rivalry paradigm by Hesse and Tsao (2020) tracks conscious content using eye position as subjects follow fixation points linked to the rivaling stimuli. However, it remains unclear whether perceptual changes arise spontaneously or are induced by external factors such as fixation shifts and saccades. We found an increased probability of perceptual switches time-locked to fixation point shifts, indicating that some switches are externally driven. To disentangle the effects of visual fixation shifts and saccades, we implemented a two-factorial design and found that saccades play a larger role in eliciting perceptual changes. We estimate that 14% of saccades trigger a switch, accounting for 24% of all perceptual transitions. Our findings provide an analysis framework and guidelines for excluding externally driven perceptual switches, enabling a clearer focus on internally generated perceptual dynamics.
Calcium channel-coupled transcription factors facilitate direct nuclear signaling
Authors: Rao Eshaan R. , Thaxton Tyler , Gama Eric , Godfrey Jack , Wei Cenfu , Lin Qiaoshan , Li Yan , Hejazi Pastor Daniel Parviz , Hansel Christian , Du Xiaofei , Gomez Christopher M. 
Published: February 2025

SummaryVGCCs play crucial roles within the CNS, in maintaining cell excitability, enabling activity- dependent neuronal development, and forming long-term memory by regulating Ca2+influx. The intracellular carboxyl-terminal domains of VGCC α1 subunits help regulate VGCC function.Emerging evidence suggests that some VGCC C-termini have functions independent of channel gating and exist as stable proteins. Here, we demonstrate that all VGCC gene family members express bicistronic mRNA transcripts that produce functionally distinct C-terminal proteins (CTPs) in tandem with full-length VGCC α1 subunits. Two of these CTPs, α1CCT and α1ACT, cycle to and from the nucleus in a Ca2+- and calmodulin-dependent fashion. α1CCT, α1ACT, and α1HCT regulate chromatin accessibility and/or bind directly to genes, regulating gene networks involved in neuronal differentiation and synaptic function in a Ca2+-dependent manner. This study elucidates a conserved process of coordinated protein expression within the VGCC family, coupling the channel function with VGCC C-terminal transcription factors.
A Pre-Bilaterian Origin of Phototransduction Genes and Photoreceptor Cells
Authors: Aleotti Alessandra , Giorgini Flaviano , Feuda Roberto 
Published: February 2025

AbstractThe evolution of vision is a major novelty in animals, playing a fundamental role in developing complex behaviours. Vision initiates with a light-triggered phototransduction cascade occurring in photoreceptor cells (PRCs). The two main PRC types, ciliary and rhabdomeric, employ both specific and common genes for phototransduction. Despite being crucial for vision, the origin and evolution of photoreceptor cells and phototransduction pathways remain unclear.Using phylogenetic methods, we studied the evolution of all phototransduction genes, elucidating their gene duplication patterns in over 80 species, including non-bilaterian metazoans and other eukaryotes. Then, we investigated the expression of phototransduction genes in available single-cell RNA-sequencing data from various animals, including non-bilaterians. By using phototransduction genes as markers, we identified putative photoreceptor-like cells across animals and compared their regulatory toolkits.Gene families encoding phototransduction components are generally ancient, predating the origin of vision. However, many phototransduction genes originated in the metazoan stem group. Moreover, putative photoreceptor cells identified in non-bilaterians appeared to express some but not all components of the two well-characterised phototransduction pathways, suggesting potential lineage-specific components involved in phototransduction. Finally, we identified conserved expression of certain transcription factors in putative PRCs in non-bilaterians, suggesting the homology of PRCs.
KYLO-0603, a novel liver-targeting, thyroid hormone receptor-β agonist for the treatment of MASH
Authors: lu Xueqin , Wang Shengjun , Du Yanchun , Xie Bixian , Chen Qingyan , Lin Jinzhen , Chen Bailing , Cui Kunyuan 
Published: February 2025

AbstractMetabolic dysfunction–associated steatohepatitis (MASH) is a progressive liver disease associated with liver-related complications and death. Kylo-0603 is a novel agonist for the thyroid hormone receptor β (THR-β) that has been developed by merging the structures of three acetylgalactosamine (GalNAc)-modified ASPGR ligands with a triiodothyronine (T3) analog. This unique design allows for both THR-β activation and targeted delivery to hepatocytes, significantly reducing the risk of adversed effects related to increased systemic thyroid hormone-like effects. Additionally, it effectively lowers serum cholesterol by as much as 69.2% and low-density lipoprotein cholesterol (LDL-C) levels by up to 88.2% in the MASH mouse model. Meanwhile, Kylo-0603 was shown to reduce steatosis by up to 1.3 points (P < 0.001), inflammation by 1.8 points (P < 0.0001), and ballooning by 0.8 points (P < 0.01). The non-alcoholic steatohepatitis (NASH) activity score (NAS) decreased by up to 3.7 points (P < 0.0001), and the fibrosis score dropped by 0.6 points (P < 0.05). These findings suggest that Kylo-0603 is effective in enhancing liver tissue NASH status and inhibiting fibrosis progression. In summary, Kylo-0603, as a highly both tissue and target selective and low-toxicity THR-β agonist, shows significant promise for treating MASH and is likely to emerge as a new therapeutic option for patients with this condition.
Disruptions in Outer Membrane-Peptidoglycan Interactions Enhance Bile Salt Resistance in O-antigen-ProducingE. coli
Authors: Qin Jilong , Hong Yaoqin , Vollmer Waldemar , Morona Renato , Totsika Makrina 
Published: February 2025

AbstractBile salts (BS) are derived from cholesterol in the liver and act as antimicrobial agents in the intestines by disrupting bacterial cell membranes and inducing oxidative stress. The gut bacteriumE. coliis naturally resistant to BS, including the model strain K12 that produces a truncated LPS without O-antigen (OAg). Paradoxically, restoring a wild-type like LPS with OAg sensitisesE. coliK12 to exogenous BS. In this study, we investigate this phenomenon. We show that mutations causing truncation of the LPS core oligosaccharide render these strains even more susceptible to BS, similar to the mutant strain MG1655-SΔwaaLdefective in OAg ligase, primarily due to the accumulation of the lipid-linked intermediate UndPP-OAg. Through the characterisation of BS-resistant suppressor mutants of MG1655-SΔwaaL, we identify key genetic disruptions involved in resistance. Notably, we observed the highest BS resistance in strains with a weaker connection between the outer membrane (OM) and peptidoglycan (PG), including strains lacking the major OM-anchored, PG-binding proteins OmpA or Lpp, or expressing versions of these that lack PG-binding. Our data suggest that BS-induced stress in OAg-producingE. coliis due to the spatial constraints between OM and PG, and that mutations disrupting OM-PG interactions alleviate this stress, enhancing BS resistance. These findings provide new insights into a major challengeE. colifaces in the gut environment where it needs to produce OAg for stable colonisation and resists BS.E. colican only survive BS exposure by fine-tuning the connectivity between its cell envelope layers, which highlights a potential target for modulating bacterial responses to BS in the gut.Author summaryEnteric bacteria residing in the human gut must withstand the host-derived antimicrobial agents, bile salts (BS), but the underlying resistance mechanisms are not fully elucidated. This study investigates the BS resistance mechanisms in O-antigen (OAg)-producingEscherichia coliK-12. We show that truncation of lipopolysaccharide (LPS) core oligosaccharides or restoration of OAg production increases BS sensitivity due to the accumulation of UndPP-OAg intermediates. By analysing suppressor mutants, we identify key genetic disruptions, particularly affecting the level of outer membrane-peptidoglycan (OM-PG) interactions involving OmpA and Lpp, which confer heightened BS resistance. Our findings highlight how BS-induced stress is linked to spatial constraints between the OM and PG layer, offering new insights into bacterial adaptation to BS stress. This research may provide new targets for therapeutic interventions to modulate gut microbial responses to BS.
DiatomNet: An automatic Diatom genus identification system through microscopic images and Deep Learning
Authors: Villar Pedro , Casado Jacobo , Fernández David , Sánchez Pedro , Tabik Siham 
Published: February 2025

ABSTRACTDiatoms are microscopic organisms belonging to the algae kingdom. They adapt to the ecosystem and modify their shape and texture depending on hundreds of ecosystem variables. Hence, these micro-organism are considered as the most accurate indicator to measure water quality. Commonly, the recognition of the class of diatoms in a microscopic image has always been done by expert biologists knowledgeable about the morphometric characteristics of these organisms. This work proposes a new automatic diatom genus recognition system from microscopic images using state-of-the-art deep CNNs. In particular, 1) we developed a public high quality database organized into 44 genus-level diatom classes, 2) designed a robust diatom classification model, and 3) provided a user-friendly interface to utilize our automatic diatom recognition tool.
Tiny killers: first record of rhabdocoel flatworms feeding on water flea embryos
Authors: Tüzün Nedim , Lemke Nina , Diez Yander L. , Artois Tom , Monnens Marlies 
Published: February 2025

ABSTRACTFlatworms are increasingly recognized for their ecological significance and potential to disrupt local fauna, yet most research has focused on conspicuous, larger planarians. Smaller flatworms, or microturbellarians, are often top predators within meiofaunal food webs. Here, we report a novel interaction involving a rhabdocoel microturbellarian,Strongylostoma simplex, predating onDaphniawater flea embryos. We identified the flatworm based on histological serial sections and recognized key diagnostic traits. In a laboratory experiment, we tested for survival and offspring production ofDaphnia magnain the presence and absence ofStrongylostoma simplex. Exposure to flatworms caused a drastic reduction in water flea fitness, indicated by the strongly reduced survival and offspring production in flatworm-exposedDaphnia. This finding corroborates our visual observations of egg predation by these flatworms, and suggests a strong pressure onDaphniapopulation dynamics. This is particularly concerning for small or isolated water bodies, such as the water reservoirs located in a cemetery in Berlin in which we documented this interaction, as this would increase the probability of encounters between flatworms and water fleas. AsDaphniaplay an essential role in regulating phytoplankton blooms and supporting higher trophic levels in freshwater ecosystems, understanding the ecological consequences of potentially invasive predatory flatworms is imperative.
Brain bases for navigating acoustic features
Authors: Billig Alexander J. , Sedley William , Gander Phillip E. , Kumar Sukhbinder , Lad Meher , Chait Maria , Mohammadi Yousef , Berger Joel I. , Griffiths Timothy D. 
Published: February 2025

AbstractWhether physical navigation shares neural substrates with mental travel in other behaviourally relevant domains is debated. With respect to sound, pure tone working memory in humans elicits hippocampal as well as auditory cortical and inferior frontal activity, and rodent work suggests that hippocampal cells that usually track an animal’s physical location can also map to tone frequency when task-relevant. We generated a sound dimension based on the density of random-frequency tones in a stack, resulting in a percept ranging from low- (“beepy”) to high-density (“noisy”). We established that unlike tone frequency, which listeners automatically associate with vertical position, this density dimension elicited no consistent spatial mapping. During functional magnetic resonance imaging, human participants (both sexes) held in mind the density of a series of tone stacks and, after a short maintenance period, adjusted further stacks to match the target (“navigation”). Density was represented most strongly in bilateral non-primary auditory cortex, specifically bilateral planum polare. Encoding and maintenance activity in hippocampus, inferior frontal gyrus, planum polare and posterior cingulate was positively associated with subsequent navigation success. Bilateral inferior frontal gyrus and hippocampus were among regions with elevated activity during navigation, compared to a parity-judgment condition with closely matched acoustics and motor demands. Bilateral orbitofrontal cortex was more active when navigation was toward a target density than when participants adjusted density in a control condition with no particular target. We find that self-initiated travel along a non-spatial auditory dimension engages a brain system overlapping with that supporting physical navigation.Significance StatementWork in rodents suggests that navigation in physical space and the active analysis of sounds share a neural substrate in the hippocampus, supporting the use of common computational mechanisms. We examined the human brain system for navigation through an acoustic environment to a remembered target. In addition to high-level auditory cortex we demonstrate involvement of the hippocampus along with sites in frontal and cingulate cortex that also support physical navigation.
Systematic silencing of oncogenic fusion transcripts with ultra-precise CRISPR-Cas13b
Authors: Hu Wenxin , Chen Honglin , Casan Joshua ML , Shembrey Carolyn , He Steven , Brown Lauren M , Hughes Timothy P. , White Deborah L. , De Weck Antoine , Voskoboinik Ilia , Trapani Joseph A , Ekert Paul G , Sadras Teresa , Fareh Mohamed 
Published: February 2025

ABSTRACTOncogenic gene fusions are key drivers of cancer, yet most remain untargetable by current therapies. Here, we establish CRISPR-PspCas13b as a personalizable platform for systematic silencing of various fusion transcripts. We reveal that recognition and cleavage of the breakpoint sequence by PspCas13b disrupts the fusion transcript, resulting in unexpected RNA nicking and ligation near the cleavage site, which generates out-of-frame, translation-incompetent transcripts. This approach efficiently degrades canonical and drug-resistant BCR::ABL1 mutants (e.g., T315I), a primary cause of resistance to tyrosine kinase inhibitors (TKIs) and relapse in chronic myeloid leukemia (CML). Silencing T315I BCR::ABL1 mRNA in drug-resistant CML cells triggers extensive transcriptomic, proteomic, and phosphoproteomic remodelling, causing erythroid differentiation and apoptosis. Beyond BCR-ABL1 mutants, personalized design ofPspCas13b effectively silences other undruggable fusions, including RUNX1::RUNX1T1 and EWSR1::FLI1, key drivers in acute myeloid leukemia and in Ewing sarcoma, respectively. Collectively, this study establishes a framework for systematic, precise, and personalizable targeting of otherwiseundruggableor drug-resistant oncogenic transcripts.
Specific cell states underlie complex tissue regeneration in spiny mice
Authors: Rivadeneira Emilio Oviedo , Allen Robyn , Adam Mike , Seifert Ashley W. 
Published: February 2025

ABSTRACTCell proliferation is an elemental feature of epimorphic regeneration in vertebrate taxa. We previously reported that in contrast to fibrotic repair observed in laboratory mouse (Mus) strains, highly regenerative spiny mice (Acomysspp.) exhibit cell cycle progression and cell proliferation to faithfully replace missing tissue. However, little is known about proliferation dynamics, and specific cell types and states that may contribute to complex tissue regeneration in mammals. Using temporal pulse-chase experiments, we show that stromal cells inAcomys dimidiatusrapidly re-enter the cell cycle in response to injury and maintain tight spatiotemporal control of cell cycle progression to restrict the proliferative population to a distal area relative to the injury. Conversely,Musstromal cells incorporate thymidine analogs without cell division supporting an S-phase arrest after D10. Deploying immunostaining and scRNA-seq, we identify several key cell types (CRABP1+, αSMA+) differentially associated with regenerating versus scar tissue. Importantly, our single cell data revealed distinct gene expression profiles for cross-species stromal cell types, identifying cell states specific for regenerative or fibrotic healing. While CRABP1+ fibroblasts are enriched inAcomysears before and after injury, similar fibroblasts enriched in young, postnatalMusears remain unable to promote regeneration. Our data underscore the finely regulated dynamics of proliferating cells during regeneration and emphasize that regeneration depends on multiple factors including the presence of specific cell types and the ability of cells to acquire specific states.Key Conclusions-Differentiated cells inAcomys,MusandDaniore-enter the cell cycle in response to injury, while homeostatic cycling cells contribute to blastema formation inAmbystoma-Pulse-chase thymidine analog labeling shows tight spatiotemporal control of proliferating stromal cells during regeneration inAcomys.-Following injury, CRABP1 and αSMA are expressed in distinct stromal cell populations inAcomysbut are co-expressed inMusstromal cell populations.-Species-specific cell states underlie regenerative and fibrotic repair-CRABP1+ cells are lost during embryonic development inMusear pinna but are retained inAcomysto adulthood.-Young neonatalMuswith abundant CRABP1+ cells still fail to execute regenerative healingSUMMARY STATEMENTComparing regenerative vs. fibrotic healing, we identify injury-induced cell states associated with persistent cell cycle progression and complex tissue regeneration in mammals.
Pallidal prototypic neuron and astrocyte activities regulate flexible reward-seeking behaviors
Authors: Kang Shinwoo , Yang Minsu Abel , Bennett Aubrey , Kang Seungwoo , Lee Sang Wan , Choi Doo-Sup 
Published: February 2025

AbstractBehavioral flexibility allows animals to adjust actions to changing environments. While the basal ganglia are critical for adaptation, the specific role of the external globus pallidus (GPe) is unclear. This study examined the contributions of two major GPe cell types—prototypic neurons projecting to the subthalamic nucleus (ProtoGPe→STNneurons) and astrocytes—to behavioral flexibility. Using longitudinal operant conditioning with context reversals, we found that ProtoGPe→STNneurons dynamically represent contextual information correlating with behavioral optimality. In contrast, GPe astrocytes exhibited gradual contextual encoding independent of performance. Deleting ProtoGPe→STNneurons impaired adaptive responses to changing action-outcome contingencies without altering initial reward-seeking acquisition, highlighting their specific role in enabling behavioral flexibility. Furthermore, we discovered that ProtoGPe→STNneurons integrate inhibitory striatal and excitatory subthalamic inputs, modulating downstream basal ganglia circuits to support flexible behavior. This research elucidates the complementary roles of ProtoGPe→STNneurons and astrocytes in cellular mechanisms of flexible reward-seeking behavior.
Development of the zebrafish anterior lateral line system is influenced by underlying cranial neural crest
Authors: Venkataraman Vishruth , McGrory Noel H. , Christiansen Theresa J. , Acedo Joaquin Navajas , Coates Michael I. , Prince Victoria E. 
Published: February 2025

AbstractThe mechanosensory lateral line system of aquatic vertebrates comprises a superficial network of distributed sensory organs, the neuromasts, which are arranged over the head and trunk and innervated by lateral line nerves to allow detection of changes in water flow and pressure. While the well-studied zebrafish posterior lateral line has emerged as a powerful model to study collective cell migration, far less is known about development of the anterior lateral line, which produces the supraorbital and infraorbital lines around the eye, as well as mandibular and opercular lines over the jaw and cheek. Here we show that normal development of the zebrafish anterior lateral line system from cranial placodes is dependent on another vertebrate-specific cell type, the cranial neural crest. We find that cranial neural crest and anterior lateral lines develop in close proximity, with absence of neural crest cells leading to major disruptions in the overlying anterior lateral line system. Specifically, in the absence of neural crest neither supraorbital nor infraorbital lateral lines fully extend, such that the most anterior cranial regions remain devoid of neuromasts, while supernumerary ectopic neuromasts form in the posterior supraorbital region. Both neural crest and cranial placodes contribute neurons to the lateral line ganglia that innervate the neuromasts and in the absence of neural crest these ganglia, as well as the lateral line afferent nerves, are disrupted. Finally, we establish that as ontogeny proceeds, the most anterior supraorbital neuromasts come to lie within neural crest-derived frontal and nasal bones in the developing cranium. These are the same anterior supraorbital neuromasts that are absent or mislocated in specimens lacking neural crest cells. Together, our results establish that cranial neural crest and cranial placode derivatives function in concert over the course of ontogeny to build the complex cranial lateral line system.HighlightsThe anterior lateral line and cranial neural crest develop in close proximityAbsence of neural crest disrupts anterior lateral line developmentAbsence of neural crest disrupts lateral line ganglion morphology and innervationEarly interactions of neural crest and placodes prefigure later anatomical interactions
Do CEO and board characteristics matter in the ESG performance of their firms?
Authors: Oyinlola Blessing 
Published: February 2025

Purpose
This study investigates the impact of chief executive officers (CEOs’) and board members’ personal characteristics on their firms’ environmental, social and governance (ESG) performance.

Design/methodology/approach
Using a sample of 120,834 firm-year observations, this study used fixed-effect ordinary least squares regression analysis to empirically identify which characteristics of the CEO and board members are linked to ESG performance.

Findings
The results from analyzing archival data of privately held Finnish firms show that education level positively influences ESG performance, while age and income negatively affect total ESG performance.

Research limitations/implications
The findings highlight the importance of these characteristics in promoting ESG practices in private firms. Therefore, it will enable regulators to encourage diversity among the board members and the CEO, thereby helping to identify potential areas for improvement in corporate governance and leadership practices. The results also provide insights into how organizations can better align their actions with their values and goals.

Originality/value
This study adds to existing literature on corporate governance and ESG performance by identifying the specific personal characteristics of the directors, such as previous conviction, age, income and marital status, and their influences on ESG performance in privately held firms in Finland.