bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transitions from monotonic to tuned responses in recurrent neural network models during timing prediction
Authors: Hendrikx Evi , Manns Daniel , van der Stoep Nathan , Testolin Alberto , Zorzi Marco , Harvey Ben M. 
Published: August 2024

AbstractThe brain exhibits a gradual transition in responses to visual event duration and frequency through the visual processing hierarchy: from monotonically increasing to timing-tuned responses. Over their hierarchies, properties of both response types are progressively transformed. Here, we implement simulations based on artificial neural networks to investigate the requirements of neural systems for the emergence of such responses and their properties’ transformations. We see that recurrent networks develop monotonic responses whose properties’ progressions over network layers resemble those over brain areas. Responses to another sensory quantity, Furthermore, recurrent networks can further develop tuned responses, but only with training, a gradual transition between monotonic and tuned responses emerges. Particularly, if this training is done on predictable sequences, the tuned properties’ progressions resemble those observed in the brain. These results suggest that the emergence of visual timing-tuned responses and the subsequent hierarchical transformations of these responses result from recurrent neural computation and predictive processing of sensory event timing.
Diverse RNA Structures Induce PRC2 Dimerization and Inhibit Histone Methyltransferase Activity
Authors: Song Jiarui , Yao Liqi , Gooding Anne R. , Thron Valentin , Kasinath Vignesh , Cech Thomas R. 
Published: August 2024

SUMMARYMethyltransferase PRC2 (Polycomb Repressive Complex 2) introduces histone H3K27 trimethylation, a repressive chromatin mark, to tune the differential expression of genes. PRC2 is precisely regulated by accessory proteins, histone post-translational modifications and, notably, RNA. Research on PRC2-associated RNA has mostly focused on the tight-binding G-quadruplex (G4) RNAs, which inhibit PRC2 enzymatic activity in vitro and in cells. Our recent cryo-EM structure provided a molecular mechanism for G4 RNA inactivating PRC2 via dimerization, but it remained unclear how diverse RNAs associate with and regulate PRC2.Here, we show that a single-stranded G-rich RNA and an atypical G4 structure called pUG-fold unexpectedly also mediate near-identical PRC2 dimerization resulting in inhibition of PRC2 methyltransferase activity. The conformational flexibility of arginine-rich loops within subunits EZH2 and AEBP2 of PRC2 can accommodate diverse RNA secondary structures, resulting in protein-RNA and protein-protein interfaces similar to those observed previously with G4 RNA. Furthermore, we address a recent report that failed to detect PRC2-associated RNAs in living cells by demonstrating the insensitivity of PRC2-RNA interaction to photochemical crosslinking. Our results support the significance of RNA-mediated PRC2 regulation by showing that this interaction is not limited to a single RNA secondary structure, consistent with the broad PRC2 transcriptome containing many G-tract RNAs incapable of folding into G4 structures.
TRAIL receptor agonist TLY012 in combination with PD-1 inhibition promotes tumor regression in an immune-competent mouse model of pancreatic ductal adenocarcinoma
Authors: Louie Anna D. , Huntington Kelsey E. , Lee Young , Mompoint Jared , Wu Laura Jinxuan , Lee Seulki , Miner Thomas J. , El-Deiry Wafik S. 
Published: August 2024

AbstractPancreatic ductal adenocarcinoma (PDAC) has an immunosuppressed, apoptosis-resistant phenotype. TLY012 is a pegylated recombinant Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL), an orphan drug for chronic pancreatitis and systemic sclerosis. Innate immune TRAIL signaling suppresses cancer. We hypothesized that combination of immune checkpoint-blocking anti-PD-1 antibody and TLY012 would have synergistic anti-tumor efficacy in immune-competent PDAC-bearing mice. PDAC tumor-bearing C57Bl/6 mice treated 10 mg/kg anti-mouse PD-1 antibody twice weekly and 10 mg/kg TLY012 three times weekly had reduced tumor growth and tumor volume at 70 days compared to either drug alone (all p<0.005). B-cell activating factor (BAFF), which promotes PDAC tumors, decreased to 44% of control mice with dual treatment at 7 days and remained decreased at 3 months. Long-term dual treatment showed the highest levels of proinflammatory cytokines interferon gamma (average 5.6 times control level, p=0.046), CCL5 (average 14.1 times control level, p=0.048), and interleukin-3 (IL-3, average 71.1 times control level, p=0.0053). Flow cytometry showed trends toward decreased circulating regulatory T cells, increased NK cells, and a higher proportion of CD8+ T cells within tumors in dual treatment group. In summary, combination of anti-PD-1 and TLY012 prevented growth of PDAC in an immunocompetent mouse model while increasing tumor-infiltrating CD8+ T cells, decreasing circulating T-regulatory cells and altering cytokine expression of CCL5, interferon gamma and IL-3 to promote proinflammatory, antitumor effects. Combining TLY012 and anti-mouse PD-1 creates changes in immune cell and cytokine levels to induce a more proinflammatory immune environment that contributes to decreased PDAC tumor growth.
RepeatAscarischallenge reduces worm intensity through gastric cellular reprograming
Authors: Wu Yifan , Suarez-Reyes Charlie , Kneubehl Alexander R. , Weatherhead Jill E. 
Published: August 2024

AbstractAscariasis (roundworm) is the most prevalent parasitic nematode infection worldwide, impacting approximately 500 million people predominantly in low- and middle-income countries (LMICs). While people of all ages are infected withAscaris, infection intensity (defined by worm burden) paradoxically peaks in pre-school and school aged children but then declines with age. The cause of age-dependentAscarisworm intensity is not well understood but may be dependent on cellular changes in mucosal barrier sites. We have previously found that the gastric mucosa is a critical barrier site forAscarisinfection. Following oral ingestion ofAscariseggs, larvae use AMCase secreted by gastric chief cells and acid secreted by gastric parietal cells to hatch. Once hatched, larvae translocate across the gastric mucosa to initiate the larval migratory cycle. However, inducing mucosal injury with administration of Tamoxifen induces mucosa cellular changes that impairsAscarishatching and reduces larval translocation across the gastric mucosa. In this study we established a repeatedAscaris suumchallenge mouse model and evaluated if repeated Ascaris challenge also lead to cellular changes in the gastric mucosal barrier. We found that repeatedAscarischallenge caused cellular changes in the gastric mucosa which reduced worm intensity in the liver independent of the adaptive immune response. Thus, in endemic regions, where individuals experience recurrent infection throughout their lives, gastric cellular changes may be a key mechanism leading to the observed age-dependentAscarisworm intensity changes from childhood to adulthood.
Developmental transformations of Purkinje cells tracked by DNA electrokinetic mobility
Authors: Brandenburg C. , Crutcher G.W. , Romanowski A.J. , Donofrio S.G. , Duraine L.R. , Owusu-Mensah R.N.A. , Sugihara I. , Blatt G.J. , Sillitoe R.V. , Poulopoulos A. 
Published: August 2024

ABSTRACTBrain development relies on orchestrated placement and timing of neurogenesis in progenitor zones to produce the expansive cellular diversity of the brain. We took advantage of bioelectric interactions between DNA and embryonic tissue to perform “stereo-tracking”, a developmental targeting strategy that differentially labels cells positioned at different depths within intact progenitor zones. This three-dimensional labeling was achieved by delivery of plasmids with distinct electrokinetic mobilities into neural progenitor zonesin utero. We applied stereo-tracking with light sheet imaging in the cerebellum and identified that Purkinje cells follow embryonically committed developmental trajectories linking distinct progenitor zone fields to the topography of the mature cerebellar cortex. In the process of stereo-tracking, we identified a previously unreported subcellular structure on the axon initial segment of Purkinje cells. These structures, we termed “axon bubbles”, are developmentally timed and differentially labeled by lipid-modified proteins. Our findings demonstrate key rules that orchestrate the stereotyped transformations from fetal progenitors into mature networks of neuronal circuits, and demonstrate the potential of progenitor zone stereo-tracking to reveal new biology within intact developing systems.
Variational inference of single cell time series
Authors: Xu Bingxian , Braun Rosemary 
Published: August 2024

AbstractTime course single–cell RNA sequencing (scRNA-seq) enables researchers to probe genome–wide expression dynamics at the the single cell scale. However, when gene expression is affected jointly by time and cellular identity, analyzing such data — including conducting cell type annotation and modeling cell type–dependent dynamics — becomes challenging. To address this problem, we propose SNOW (SiNgle cell flOW map), a deep learning algorithm to deconvolve single cell time series data into time– dependent and time–independent contributions. SNOW has a number of advantages. First, it enables cell type annotation based on the time–independent dimensions. Second, it yields a probabilistic model that can be used to discriminate between biological temporal variation and batch effects contaminating individual timepoints, and provides an approach to mitigate batch effects. Finally, it is capable of projecting cells forward and backward in time, yielding time series at the individual cell level. This enables gene expression dynamics to be studied without the need for clustering or pseudobulking, which can be error prone and result in information loss. We describe our probabilistic framework in detail and demonstrate SNOW using data from three distinct time course scRNA-seq studies. Our results show that SNOW is able to construct biologically meaningful latent spaces, remove batch effects, and generate realistic time–series at the single–cell level. By way of example, we illustrate how the latter may be used to enhance the detection of cell type–specific circadian gene expression rhythms, and may be readily extended to other time–series analyses.
Rapid Visual Engagement in Neural Processing of Detailed Touch Interactions
Authors: Smit Sophie , Ramírez-Haro Almudena , Quek Genevieve L. , Varlet Manuel , Moerel Denise , Grootswagers Tijl 
Published: August 2024

AbstractTouch perception is an inherently multisensory process in which vision plays an essential role. However, our understanding of how vision encodes sensory and emotional-affective aspects of observed touch, and the timing of these processes, is still limited. Here we address this gap by investigating the neural dynamics of visual touch observation by analysing electroencephalographic (EEG) data from participants viewing detailed hand interactions from the Validated Touch-Video Database. We examined how the brain encodes basic body cues such as hand orientation and viewing perspective, in addition to sensory aspects, including the type of touch (e.g., stroking vs. pressing; hand vs. object touch) and the object involved (e.g., knife, brush), as well as emotional-affective dimensions. Using multivariate decoding, information about body cues was present within 60 ms, with sensory and emotional details, including valence, arousal, and pain present around 130 ms, demonstrating efficient early visual processing. Threat was most clearly identified by approximately 265 ms, similarly involving visual regions, suggesting that such evaluations require slightly extended neural engagement. Our findings reveal that bottom-up, automatic visual processing is integral to complex tactile assessments, important for rapidly extracting both the personal relevance and the sensory and emotional dimensions of touch.
Sex and morph variation in activity from early ontogeny to maturity in ruffs (Calidris pugnax)
Authors: Rohr-Bender Veronika A. , Kupán Krisztina , Lopez-Nava Guadalupe , Forstmeier Wolfgang , Hertel Anne , Razumov Vitali , Martin Katrin , Kempenaers Bart , Küpper Clemens 
Published: August 2024

AbstractIntraspecific variation provides the substrate for the evolution of organisms. Ruffs show exceptional phenotypic variation in physiology, appearance and behaviour linked to variation between sexes and male alternative reproductive tactics (ARTs). The male ARTs are associated with the evolution of separate morphs, which are encoded by an autosomal supergene. However, the effects of the supergene on females and chicks are much less well understood. In particular, it is still unknown, whether females also show morph-specific behavioural variation, when behavioural differences emerge during ontogeny, and whether behavioural differences can be detected outside of the breeding context. To address these knowledge gaps, we repeatedly measured the activity in an unfamiliar environment, also known as exploration behaviour, of 109 hand-raised young ruffs throughout their first two years of life. We used automated tracking in an open field arena, and quantified the distance moved within 10 minutes to examine behavioural differences between sexes, morphs and individuals. The activity of young ruffs rapidly increased during the first month after their crouching reflex, a response to potential threats, subsided. Repeatability of individual activity was initially low but increased throughout juvenile ontogeny and was high (R = 0.5) from day 21 onwards. Variation in activity was clearly sex-linked with females moving more than males, indicating potential energetic trade-offs accompanying the strong sexual size dimorphism. In contrast, morph differences in activity remained inconsistent and elusive, both in females and in males. Our results indicate that in species where much of the known behavioural variation is linked to mating tactics, a non-reproductive behaviour can show between-individual variation and clear sex differences, whereas morph differences appear less pronounced.
GPRC6A as a novel kokumi receptor responsible for enhanced taste preferences by ornithine
Authors: Yamamoto Takashi , Ueji Kayoko , Mizuta Haruno , Inui-Yamamoto Chizuko , Kumamoto Natsuko , Shibata Yasuhiro , Ugawa Shinya 
Published: August 2024

AbstractThe concept of “kokumi,” which refers to an enhanced and more delicious flavor of food, has recently generated considerable interest in food science. However, kokumi has not been well studied in gustatory physiology, and the underlying neuroscientific mechanisms remain largely unexplored. Our previous research demonstrated that ornithine (L-ornithine), which is abundant in shijimi clams, enhanced taste preferences in mice. The present study aimed to build on these findings and investigate the mechanisms responsible for kokumi in rats. In two-bottle preference tests, the addition of ornithine, at a low concentration that did not increase the favorability of this substance alone, enhanced the animals’ preferences for umami, sweet, fatty, salty, and bitter solutions, with the intake of monosodium glutamate showing the most significant increase. Additionally, a mixture of umami and ornithine synergistically induced significant responses in the chorda tympani nerve, which transmits taste information to the brain from the anterior part of the tongue. The observed preference enhancement and increase in taste-nerve response were abolished by antagonists of the G-protein-coupled receptor family C group 6 subtype A (GPRC6A). Furthermore, immunohistochemical analysis indicated that GPRC6A was expressed in a subset of type II taste cells in rat fungiform papillae. These results provide new insights into flavor-enhancement mechanisms, confirming that ornithine is a kokumi substance and GPRC6A is a novel kokumi receptor.
Scaling law for a buckled elastic filament in a shear flow
Authors: Sznajder Paweł , Zdybel Piotr , Liu Lujia , Ekiel-Jeżewska Maria L. 
Published: August 2024

We analyze the three-dimensional (3D) buckling of an elastic filament in a shear flow of a viscous fluid at low Reynolds number and high Péclet number. We apply the Euler-Bernoulli beam (elastica) theoretical model. We show the universal character of the full 3D spectral problem for a small perturbation of a thin filament from a straight position of arbitrary orientation. We use the eigenvalues and eigenfunctions for the linearized elastica equation in the shear plane, found earlier by Liu [] with the Chebyshev spectral collocation method, to solve the full 3D eigenproblem. We provide a simple analytic approximation of the eigenfunctions, represented as Gaussian wave packets. As the main result of the paper, we derive the square-root dependence of the eigenfunction wave number on the parameter χ̃=−ηsin2ϕsin2θ, where η is the elastoviscous number and the filament orientation is determined by the zenith angle θ with respect to the vorticity direction and the azimuthal angle ϕ relative to the flow direction. We also compare the eigenfunctions with shapes of slightly buckled elastic filaments with a non-negligible thickness with the same Young's modulus, using the bead model and performing numerical simulations with the precise numerical codes.

Published by the American Physical Society
2024
Financial structure and innovation: firm-level evidence from Africa
Authors: Ayalew Misraku Molla , Zhang Joseph H. 
Published: August 2024

PurposeThe purpose of this paper is to examine the effect of the financial structure on innovation.Design/methodology/approachWe utilize the matched firm-level data from two sources: the World Bank Enterprise Survey and the Innovation Follow-Up Survey. A total of 3,664 firms from 11 African countries are included.FindingsThe authors find a financially constrained and low technology-intensive firm that uses internal finance more than its peers is less likely to innovate. Our results also show that a firm that uses new equity and debt finance more than its peers is more likely to innovate. The results particularly suggest the significant effect of bank and trade credit finance on firms’ innovation. The extent and, in some cases, the direction of the effect of dependence on internal finance, new equity finance and debt finance on innovation vary due to the heterogeneity in firm size, age and ownership status. Corporate innovation is also associated with firm size, R&D, cooperation, staff training, public support, exportation and group membership.Practical implicationsThe management of companies, particularly financially constrained firms, should reduce their dependence on internal finance, which negatively affects their innovation. As a remedy, they could improve their reliance on new equity finance and debt finance, especially bank finance and trade credit finance, which positively affect their innovativeness.Social implicationsA pending policy task for African business leaders is to design and evaluate reforms that help create strong financial sectors willing to provide capital to a broad range of firms, particularly small and young firms.Originality/valueThis study adds new evidence to the recent surge of debate on the trade-off between going public, using debt or heavily using internal sources to finance innovative projects, and which of these is more important in promoting firm-level innovation.
Fast fashion consumption as a female competition strategy: implications for sustainable consumption
Authors: Font Carina Mae , Font Xavier 
Published: August 2024

PurposeThis research considers new and unexplored explanations of why consumers continue to engage in environmentally damaging, fast fashion consumption. It explains why rational arguments alone do not prevent fast fashion consumption or encourage consumers to move toward greater adoption of sustainable fashion consumption behaviours.Design/methodology/approachThis research compared the effects of a “neutral” control and an “intrasexual rivalry” experimental condition on: (1) likelihood to buy, and (2) willingness to pay, of frequent female fast fashion shoppers (N = 184).FindingsWomen use fast fashion as a conspicuous signal to other women, although this is not necessarily why they waste fast fashion purchases. Mating motives appear to produce a significant increase in fast fashion buying behaviour with women feeling intrasexual pressure to engage in consumption, and utilising consumption themselves as a self-promotion strategy.Practical implicationsRetailers tackling wasteful fast fashion consumption can demonstrate that sustainable consumption provides a superior conspicuous signal to fast fashion consumption, instead of solely using rational messaging.Originality/valueGrounded in evolutionary psychology, this study uses three theories of intrasexual rivalry, conspicuous consumption and conspicuous waste to understand how both the volume and variety of fast fashion consumed are used as conspicuous signals in a mate attraction context.
Are indeterminate sentenced prisoners prepared for open prison? Practical implications/applications of an exploratory study in an English open prison
Authors: Edgell Toni , Lorimer Hannah 
Published: August 2024

Purpose
Research indicates the challenges indeterminate sentenced prisoners (ISPs) face within open prison may have a potentially devastating impact on rehabilitation and prison sentence progression. The authors conducted a study in an English open prison to explore whether the closed prison environment within England and Wales is sufficiently preparing ISPs for the transition to open conditions. There is currently a gap in existing research concerning this issue, which this paper aims to narrow for the purpose of informing good practice and improving sentence progression and rehabilitation outcomes within His Majesty’s Prison and Probation Service.

Design/methodology/approach
Qualitative and exploratory. Reflexive thematic analysis was conducted to identify themes (Braun and Clarke, 2019).

Findings
Findings indicated the need for policy in closed prisons to better prepare ISPs for open prison and the need for policy in open prisons to better support ISPs during the liminal phase.

Practical implications
Findings aimed to inform consideration for improvements to enhance preparation for, and transition to, open conditions. A 17-month follow-up after dissemination of the research found evidence for the practical application of the findings at a local level within HMPPS and potential for wider applications linking to strategy and ISP initiatives.

Originality/value
If applied more widely across HMPPS in both closed and open prisons, the research findings have the potential to improve sentence progression and rehabilitation outcomes for ISPs.