bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced mRNA delivery using ultrasound-delivered click reactive anchors
Authors: Di Ianni Emilio , Jeon Jueun , Hu Huiyu , Quintana Jeremy M. , Lee Chanseo , Haidar Edwina Abou , Mohammadi Sedra , Zargani-Piccardi Ayrton , Mahamdeh Mohammed , Hernández Iván Coto , Ng Thomas S.C. , Breyne Koen , Lee Hakho , Breakefield Xandra O. , Miller Miles A. 
Published: January 2025

AbstractTherapeutic nucleic acid delivery has many potential applications, but it remains challenging to target extrahepatic tissues in a flexible and image-guided manner. To address this issue, we report a bioorthogonal pre-targeting strategy that uses focused ultrasound to promote the delivery of mRNA-loaded lipid nanoparticles (mRNA-LNP). We synthesized amphiphilic click reactive anchors (ACRAs) consisting of a phospholipid PEG-conjugate functionalized with transcyclooctene (TCO) or its companion reactive partner methyltetrazine (mTz), yielding ACRA-TCO and ACRA-mTz. ACRA derivatives were screened for cellular activity, yielding functionalized DOPE-PEG (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N- (polyethylene glycol)) derivatives outperforming those containing saturated lipid or branched PEG. Nanobubbles encapsulating ultrasound-responsive gas precursor delivered ACRA-TCO to targeted cells and tissues using focused ultrasound, and this pre-targeting promoted the subsequent delivery of mRNA- LNP functionalized with companion ACRA-mTz. In cell cultures and in mice, ultrasound pre-targeting enhanced the accumulation of mTz-functionalized small molecule and nanoparticle compounds by 75% and 3.6-fold, respectively, and increased gene expression using mRNA-LNPin vivo. Taken together, this report presents a modular, ultrasound-enabled strategy for enhancing nucleic acid delivery in targeted tissues.
A saga of agonistic interactions in house crickets (Acheta domesticus): A direct and indirect effects perspective
Authors: Sekhar M. A. , Rothamer Brooke A. , Gillam Erin , Dochtermann Ned A. 
Published: January 2025

AbstractAgonistic behaviours are widely observed across multiple taxa and are critical in shaping hierarchies, influencing resource acquisition, survival, and reproductive success. Individuals often alter their behaviour in response to the traits of others, referred to as indirect effects. Individuals also differ in their mean behavioural responses, referred to as direct effects. The combination of indirect and direct effects produce the observed social interactions. Importantly, these effects are typically measured on isolated parts of the full sequence of behaviors and traits expressed during social interactions. Here, we used house crickets,Acheta domesticus, to investigate how direct and indirect effects shape behaviors and traits across an agonistic interaction. We found that the probability of initiating aggression, but not contact, was influenced by both direct and indirect effects independent of mass. Amplitude, peak frequency, and pulse duration of stridulations occurring during agonistic interactions were influenced by direct effects but were not strongly influenced by indirect effects. These results demonstrate that the strength of indirect and direct effects vary over the course of an agonistic interaction and differentially affect the specific components of these interactions. Understanding when and how these effects are important is necessary for understanding agonistic behaviour and its evolution.
Molecular determinants of RNase MRP specificity and function
Authors: Smith Eric M. , Ly Jimmy , Haug Sofia , Cheeseman Iain M. 
Published: January 2025

AbstractRNase MRP and RNase P are evolutionarily related complexes that facilitate rRNA and tRNA biogenesis, respectively. The two enzymes share nearly all protein subunits and have evolutionarily related catalytic RNAs. Notably, RNase P includes a unique subunit, Rpp21, whereas no RNase MRP-specific proteins have been found in humans, limiting molecular analyses of RNase MRP function. Here, we identify the RNase MRP-specific protein, C18orf21/RMRPP1. RMRPP1 and Rpp21 display significant structural homology, but we identify specific regions that drive interactions with their respective complexes. Additionally, we reveal that RNase MRP is required for 40S, but not 60S, ribosome biogenesis uncovering an alternative pathway for ribosome assembly. Finally, we identify Nepro as an essential rRNA processing factor that associates with the RNase MRP complex. Together, our findings elucidate the molecular determinants of RNase MRP function and underscore its critical role in ribosome biogenesis.
Prey capture learning drives critical period-specific plasticity in mouse binocular visual cortex
Authors: Bissen Diane , Cary Brian A. , Zhang Amanda , Sailor Kurt A. , Van Hooser Stephen D. , Turrigiano Gina G. 
Published: January 2025

SummaryCritical periods are developmental windows of high experience-dependent plasticity essential for the correct refinement of neuronal circuitry and function. While the consequences for the visual system of sensory deprivation during the critical period have been well-characterized, far less is known about the effects of enhanced sensory experience. Here, we use prey capture learning to assess structural and functional plasticity mediating visual learning in the primary visual cortex of critical period mice. We show that prey capture learning improves temporal frequency discrimination and drives a profound remodeling of visual circuitry through an increase in excitatory connectivity and spine turnover. This global and persistent rewiring is not observed in adult hunters and is mediated by TNFα-dependent mechanisms. Our findings demonstrate that enhanced visual experience in a naturalistic paradigm during the critical period can drive structural plasticity to improve visual function, and promotes a long-lasting increase in spine dynamics that could enhance subsequent plasticity.
Involvement of orexin nerves in early stage of Alzheimer’s disease model mice and preventive effect of orexin receptor antagonists
Authors: Hada Kazuhiro , Murata Yuki , Yoshiaki Ohi , Hashimoto Sana , Watanabe Hinata , Ozeki Kayoko , Saido Takaomi C , Saito Takashi , Sasaguri Hiroki , Mizoguchi Hiroyuki , Yamada Kiyofumi , Wakiya Yoshifumi 
Published: January 2025

AbstractBackgroundMild cognitive impairment (MCI) is a condition between healthy cognition and dementia with a high probability of progression to Alzheimer’s disease (AD). Elevated levels of orexin (OX) have been reported in the cerebrospinal fluid of patients with MCI and AD.ObjectiveTo investigate the efficacy of dual OX receptor antagonists (suvorexant and lemborexant) in an early-stage AD mouse model (App-KI).MethodsThe expression of theOX receptorgene, the levels of suvorexant and lemborexant in the brain after a single oral dose, and their effects on locomotor activity were investigated in wild-type mice. In addition, the cognitive function of wild-type and App-KI mice was assessed using the Y-maze test after oral administration of suvorexant or lemborexant once a day for 60 d. After the behavioral test, amyloid-beta levels were quantified in the hippocampal CA1 region of App-KI mice.ResultsThe expression of theOX receptorgene was highest in the lateral hypothalamus and was also observed in other brain regions. Drug levels peaked at 20–40 min for suvorexant and 15 min for lemborexant and declined, still detectable 24 h later. Locomotor activity was reduced after suvorexant or lemborexant administration; however, 24 h after administration, locomotor activity did not differ from the control group. In particular, the Y-maze test showed that suvorexant and lemborexant prevented cognitive impairment in App-KI mice. Furthermore, suvorexant and lemborexant suppressed amyloid-beta accumulation in the hippocampal CA1 region of App-KI mice.ConclusionThe results suggest that suvorexant and lemborexant effectively suppress the early stages of AD.
Global risk assessment of Lyme borreliosis transmission
Authors: Cobos-Mayo Marina , Martín-Taboada Adrián , Aliaga-Samanez Alisa , Segura Marina , Olivero Jesús 
Published: January 2025

ABSTRACTWe analysed the geographic risk of Lyme borreliosis taking into account the biogeography of tick vectors and carrier hosts, together with environmental and anthropogenic factors. Four pathogeographical scenarios were set in order to represent the contribution of vectors and hosts in the spatial zoonotic risk. For that propose, we built distribution models based on the occurrence of Lyme borreliosis cases in humans and ixodid vectors. BesidesIxodesspecies, we considered other ixodid ticks with potential to be vectors. These models were combined through fuzzy logic operators, according to the criteria stablished in each scenario. Finally, the transmission risk model for Lyme borreliosis which best fitted its global distribution was selected. The risk model selected considered ixodid vectors and mammal carriers as explanatory variables together with environment and anthropogenic factors.Ixodesspecies contributed to explain the geographical risk of Lyme borreliosis to larger extent than other ixodid ticks. The risk model described regions with Lyme borreliosis transmission risk where its presence is still uncertain, such as northern Africa and inland areas of western USA. Likewise, our model indicated favourable conditions for the presence of human cases in northern latitudes beyond its endemic distribution. Applying this multi-scenario methodology approach have led us to a risk model, in which the diversity of ixodid vectors and carrier hosts might modify the spatial risk without a geographical limitation.
Cellular and synaptic organization of the Octopus vertical lobe
Authors: Bidel Flavie , Meirovitch Yaron , Yang Fuming , Lichtman Jeff William , Hochner Binyamin 
Published: January 2025

SummaryUnderstanding memory formation and its influence on behavior is a central challenge in neuroscience. Associative learning networks, including the mushroom body in insects, the cerebellum in mammals, and the vertical lobe (VL) in cephalopods, typically exhibit a 3-layered architecture, characterized by divergence (fan-out) followed by convergence (fan-in), facilitating sparse sensory coding (Babadi and Sompolinsky, 2014; Lin et al., 2014; Litwin-Kumar et al., 2017; Turchetti-Maia et al., 2017). Previously, using volumetric electron microscopy, we showed that the VL uniquely comprises 22 million simple amacrine (SAM) interneurons, each receiving a singular input subject to activity-dependent long-term potentiation, contrasting with typical middle-layer interneurons (Bidel, Meirovitch et al., 2023). We also demonstrated that these SAMs provide excitatory feedforward input to the output cell layer, balanced by approximately 400,000 inhibitory complex amacrines (CAM), which are morphologically diverse and integrate numerous inputs (Bidel, Meirovitch et al., 2023). Here, we leverage the same digital tissue to explore the CAMs’ morphological diversity, identifying correlations between structure, postsynaptic site density, and synaptic input proportions, which led to the classification of CAMs into distinct groups. Further analysis of the input layer in the VL revealed a meticulous structural and synaptic compartmentalization, with distinct synaptic bouton types forming three zones that integrate different inputs towards CAMs. Additionally, we identify the potential presence of a neurogenic niche in the VL, hinting at parallels with neurogenic processes in other species and warranting further investigation, particularly in the context of learning and memory. This study deepens our understanding of the VL’s cellular and synaptic architecture, revealing both shared and unique features compared to other associative networks, and highlighting the intricate interplay of structural and functional elements in memory formation.Highlights (85 characters including space)The VL both aligns with and deviates from standard associative network featuresThe VL input layer presents a unique compartmentalization by axonal bouton typeThe minority inhibitory interneurons differentiate into unique functional subtypesMirroring the mammalian hippocampus, the VL may contain an adult neurogenic niche
Electroencephalographic responses before, during, and after upper limb paired associative stimulation
Authors: Shikauchi Yumi , Uehara Kazumasa , Okazaki Yuka O. , Kitajo Keiichi 
Published: January 2025

AbstractPaired associative stimulation (PAS) is a non-invasive protocol involving repeated stimulus pairs to activate two cortical areas alternately, inducing Hebbian-like plasticity. However, its neurophysiological impacts remain unclear. To determine the changes that occur in the brain during PAS, brain activity during PAS must be measured and distinguished from the electromagnetic artifacts produced by the stimulation. Here, we present a novel dataset of electroencephalography (EEG) measurements during PAS with an inter-stimulus-interval of 25 ms (PAS25, expected to induce long-term potentiation-like changes) or 35 ms (PAS35, no expected change). This dataset includes raw data and pre-processed data with electromagnetic artefacts removed. he right ulnar nerve’s electrical stimulation preceded transcranial magnetic stimulation to the left primary motor cortex in both cases. EEG was measured before and after the PAS sessions, with only electrical or magnetic stimulation. To demonstrate the quality of the data, we summarize the stability of the stimulation site and the event-related potentials before, during, and after PAS. This dataset will enable observing brain dynamics due to the accumulation of stimulations during PAS and differences in responsiveness to stimulations before and after PAS.
Lévy Flight Patterns in the Cortical Architecture ofMacaca mulatta
Authors: Tozzi Arturo 
Published: January 2025

ABSTRACTLévy flights (LF), a concept originating in statistical physics, describe random walks in which the step lengths follow a heavy-tailed probability distribution, often a power law. Unlike Brownian motion, where step lengths are constrained within a narrow range, LF are characterized by the coexistence of many short steps interspersed with occasional long jumps. Applying advanced computational techniques, we looked for LF-like patterns in high-resolution histological images ofMacaca mulatta(Rhesus macaque) cortical area 4 from BrainMaps.org. Step-length distributions, derived from pairwise distances between neuronal somata, exhibited heavy-tailed behavior consistent with power-law models across all samples. Maximum likelihood estimation of power-law exponents (α values: 0.87-1.08) strongly supported the heavy-tailed nature of these patterns, showing a better fit with power-law models compared to exponential or normal distributions. Connectivity analyses revealed a dual organizational structure within cortical layers: densely interconnected local clusters coexisting with sparse long-range connections. k-Nearest neighbors graphs demonstrated small-world network properties, with average clustering coefficients ranging from 0.622 to 0.630 across samples. This consistent structural organization aligns with LF principles, wherein local processing is optimized alongside global integration for efficiency and functionality. The implications extend to developmental biology, as the emergence of LF-like patterns likely reflects intrinsic self-organizing processes during embryonic and fetal development. This LF-like organization provides a natural framework for designing artificial networks that optimize performance in tasks requiring both localized specialization and global integration. Moreover, understanding the developmental origins of these patterns could guide strategies for neural repair and regeneration in stroke or neurodegenerative diseases.
Human cerebral organoids model tumor infiltration and migration supported by astrocytes in an autologous setting
Authors: Schickel Esther , Bender Tamara , Kaysan Leon , Hufgard Simone , Mayer Margot , Grosshans David R. , Thielemann Christiane , Schroeder Insa S. 
Published: January 2025

SummaryEfforts to achieve precise and efficient tumor targeting of highly malignant brain tumors are constrained by the dearth of appropriate models to study the effects and potential side effects of radiation, chemotherapy, and immunotherapy on the most complex human organ, the brain. We established a cerebral organoid model of brain tumorigenesis in an autologous setting by overexpressing c-MYC as one of the most common oncogenes in brain tumors. GFP+/c-MYChighcells were isolated from tumor organoids and used in two different culture approaches: assembloids comprising of a normal cerebral organoid with a GFP+/c-MYChightumor sphere and co-culture of cerebral organoid slices at air-liquid interface with GFP+/c-MYChighcells. GFP+/c-MYChighcells used in both approaches exhibited tumor-like properties, including overexpression of the c-MYC oncogene, high proliferative and invasive potential, and an immature phenotype as evidenced by increased expression of Ki-67, VIM, and CD133. Organoids and organoid slices served as suitable scaffolds for infiltrating tumor-like cells. Using our highly reproducible and powerful model system that allows long-term culture, we demonstrated that the migratory and infiltrative potential of tumor-like cells is shaped by the environment in which glia cells provide support to tumor-like cells.
A multi-pore model of the blood-brain barrier tight junction strands recapitulates the permeability features of wild-type and mutant claudin-5
Authors: Berselli Alessandro , Alberini Giulio , Cerioni Linda , Benfenati Fabio , Maragliano Luca 
Published: January 2025

ABSTRACTIn the blood-brain barrier (BBB), endothelial cells are joined together by multi-protein assemblies called tight junctions (TJs), which seal the paracellular space and restrict the passage of substances. Among the proteins forming BBB TJs, Claudin-5 (Cldn5) is the most abundant one. Structural models for complexes of Cldn5 and other claudins have been proposed and assessed via experimental and computational approaches. In these models, first introduced for channel-forming, selectively permeable claudins, protomers are arranged to form pores in the paracellular space that regulate transport by electrostatic and/or steric effects arising from the pore-lining residues. With limited exceptions, however, previous computational studies focused on oligomers of only a few subunits, while extended polymeric claudin strands form TJs. Here, we employ multi-microsecond all-atom molecular dynamics and free energy (FE) calculations to study two distinct models of TJ-forming Cldn5 complexes, called multi-Pore I and multi-Pore II, each comprising sixteen protomers arranged around three adjacent pores. Free energy calculations of water and ions permeation across the pores reveal that, in both models, the passage of ions is hindered by FE barriers, which are higher than in single-pore architectures. Moreover, only the multi-Pore I structural model recapitulates the effect of the G60R variant of Cldn5, making it permeable to anions. The results provide new insights into Cldn5 structure and function and validate a structural model of BBB TJs that may be useful for the study of barrier impairment in brain diseases and for developing new therapeutic approaches.
Origin of the non-Fermi-liquid behavior in
CeRh2As2
Authors: Khanenko P. , Hafner D. , Semeniuk K. , Banda J. , Lühmann T. , Bärtl F. , Kotte T. , Wosnitza J. , Zwicknagl G. , Geibel C. , Landaeta J. F. , Khim S. , Hassinger E. , Brando M. 
Published: January 2025

Unconventional superconductivity in heavy-fermion systems appears often near magnetic quantum critical points (QCPs). This seems to be the case also for CeRh2As2 (Tc ≈0.31 K). CeRh2As2 shows two superconducting (SC) phases, SC1 and SC2, for a magnetic field along the c axis of the tetragonal unit cell, but only the SC1 phase is observed for a field along the basal plane. Furthermore, another ordered state (phase I) is observed below T0≈0.48K whose nature is still unclear: Thermodynamic and magnetic measurements pointed to a nonmagnetic multipolar state, but recent µSR and nuclear quadrupole resonance/nuclear magnetic resonance (NMR) experiments have clearly detected antiferromagnetic (AFM) order below T0. Also, quasi-two-dimensional AFM fluctuations were observed in NMR and neutron-scattering experiments above T0. The proximity of a QCP is indicated by non-Fermi-liquid (NFL) behavior observed above the ordered states in both specific heat C(T)/T∝T−0.6 and resistivity ρ(T)∝T. These T dependencies are not compatible with any generic AFM QCP. Because of the strong magnetic-field anisotropy of both the SC phase and phase I, it is possible to study a field-induced SC QCP as well as a phase-I QCP by varying the angle α between the field and the c axis. Thus, by examining the behavior of the electronic specific-heat coefficient C(T)/T across these QCPs, we can determine which phase is associated with the NFL behavior. Here, we present low-temperature specific-heat measurements taken in a magnetic field as high as 21 T applied at several angles α. We observe that the NFL behavior very weakly depends on the field and the angle α, a result that is at odds with observations in standard magnetic QCPs. This suggests a nonmagnetic origin of the quantum critical fluctuations.

Published by the American Physical Society
2025
The relationship between financial statement comparability and accounting conditional and unconditional conservatism
Authors: Salehi Mahdi , Ghasemi Sarnish Toktam , Rababah Abedalqader 
Published: January 2025

PurposeThe primary objective of this study is to examine the correlation between financial statement comparability and conditional and unconditional conservatism within companies listed on the Tehran Stock Exchange (TSE).Design/methodology/approachTo achieve this, a sample of 193 companies, resulting in 1,546 firm-year observations, were listed on the TSE between 2014 and 2021. The study’s research hypotheses are assessed by applying multiple regression models.FindingsThe findings reveal a notable positive association between financial statement comparability and conditional conservatism. Additionally, the research results indicate a significant and negative connection between financial statement comparability and unconditional conservatism.Practical implicationsAccording to the findings, corporate managers may prioritize financial statement comparability to enhance conditional accounting conservatism, which might be translated as a suitable benchmark for competitors. Equity owners may decrease the agency problems associated with CEOs by emphasizing comparable financial reports, as it improves the quality of financial figures and facilitates stakeholders’ evaluation and comparison of various companies’ performances.Originality/valueA review of the relevant literature underscores the absence of research focusing on the relationship between financial statement comparability and conditional and unconditional conservatism within emerging markets. Consequently, this study aims to address this gap by investigating this relationship in the context of emerging markets and contributing to the existing body of literature in this field.