bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated calcineurin activity in primary astrocytes leads to the dephosphorylation of connexin 43 in conjunction with increased membrane permeability
Authors: Weiss Blaine E. , Kraner Susan D. , Artiushin Irina A. , Norris Christopher M.
Published: May 2024

Hyperactivation of the Ca2+/calmodulin-dependent phosphatase calcineurin (CN) is observed in reactive astrocytes associated with neuroinflammation and progressive degenerative diseases, like Alzheimer’s disease. Apart from key transcription factors (e.g. nuclear factor of activated t cells and nuclear factor-κB) very few other CN-dependent pathways have been studied in astrocytes. The hemichannel protein, connexin 43 (Cx43) is found at high levels in astrocytes and contains a CN-sensitive Ser residue near its carboxy terminus. CN-dependent dephosphorylation of Cx43 has been reported in primary astrocytes treated with injurious stimuli, but much remains unknown about CN/Cx43 interactions in the context of neuroinflammation and disease. Western blots were used to assess total Cx43 and dephosphorylated Cx43 subtypes in rat embryonic primary astrocytes treated with a hyperactive CN fragment (ΔCN, via adenovirus), or with a proinflammatory cytokine cocktail. Under similar treatment conditions, an ethidium bromide (EtBr) uptake assay was used to assess membrane permeability. Effects of ΔCN and cytokines were tested in the presence or absence of the CN inhibitor, cyclosporin A. A connexin inhibitor, carbenoxolone was also used in EtBr assays to assess the involvement of connexins in membrane permeability. Treatment with ΔCN or cytokines increased dephosphorylated Cx43 levels in conjunction with increased membrane permeability (elevated EtBr uptake). Effects of ΔCN or cytokine treatment were blocked by cyclosporine A. Treatment-induced changes in EtBr uptake were also inhibited by carbenoxolone. The results suggest that Cx43 hemichannels could be an important mechanism through which astrocytic CN disrupts neurologic function associated with neurodegenerative disease.
Protective effects of orientin against spinal cord injury in rats
Authors: Song Xiaoqing , Fan Xuliang
Published: May 2024

We aimed to study the reparative effects of orientin against spinal cord injury (SCI) in rats and explore its potential mechanisms. Sprague–Dawley rats were divided into Sham, SCI, Orientin, and SB203580 [an inhibitor of p38 mitogen-activated protein kinase (p38MAPK)] groups. In the SCI group, rats underwent Allen’s beat. SCI animals in Orientin and SB203580 groups were respectively treated with 40 mg kg−1 orientin and 3 mg kg−1 SB203580 once daily. Functional recovery was evaluated based on Basso, Beattie, and Bresnahan scoring. Histopathological analysis was performed using hematoxylin-eosin and Nissl staining. Cell apoptosis was examined by TUNEL staining. The relative quantity of apoptosis-related proteins, glial fibrillary acidic protein (GFAP), neurofilament 200 (NF200), and brain derived neurotrophic factor (BDNF) was detected via western blotting. The indices related to inflammation and oxidation were measured using agent kits. The p38MAPK/inducible nitric oxide synthase (iNOS) signaling activity was detected using real-time quantitative PCR, western blotting, and immunohistochemical staining. Orientin was revealed to effectively mitigate cell apoptosis, neuroinflammation, and oxidative stress in impaired tissues. Meanwhile, orientin exerted great neuroprotective effects by abating GFAP expression, and up-regulating the expression of NF200 and BDNF, and significantly suppressed the p38MAPK/iNOS signaling. Orientin application could promote the repair of secondary SCI through attenuating oxidative stress and inflammatory response, reducing cell apoptosis and suppressing p38MAPK/iNOS signaling.
Is the Electroconvulsive Therapy Video on YouTube Supportive Information for Patients and Their Primary Caregivers?
Authors: Abu Sabra Mohammad A. , Al Kalaldeh Mahmoud , AlOsta Mohammad R.
Published: May 2024

Background

Electroconvulsive therapy (ECT) is a significant contemporary medical treatment modality for various mental disorders that have not responded to other treatments. YouTube is a valuable place to get health-related educational content that can have a big impact on patients' and their primary caregivers' behaviors and decisions.

Objective

The aim of the study is to analyze the content of YouTube videos related to ECT to investigate the quality and reliability of videos as supportive information for patients and their primary caregivers.

Methods

A total of 250 videos related to ECT that are available on YouTube were analyzed. The Global Quality Scale and the modified DISCERN tool were used to assess the quality and reliability of the videos. Details of the content of the video, caregiver appearance, methods of information presentation, source of the video, and video parameters were analyzed as well.

Result

The analysis revealed that the median total score of Global Quality Scale was 3 (interquartile range, 2; min–max, 1–5), which means the video quality was medium. The median total score of the modified DISCERN tool was 3 (interquartile range, 1; min–max, 0–5), which means the videos were highly reliable. Most of the video sources in the included videos were educational (41.2%, n = 103) from formal caregivers, and there was no significant difference between Global Quality Scale scores, video parameters, and modified DISCERN scores.

Conclusions

YouTube is considered a supportive source of information related to ECT but needs more encouragement from formal caregivers to disseminate high-quality and reliable healthcare content on YouTube platforms to ensure access to accurate information.
Shake it off: exploring drivers and outcomes of autotomy in marine invertebrates
Authors: Jobson Sara , Hamel Jean-François , Mercier Annie
Published: May 2024

Autotomy refers to self-amputation where the loss of a limb or organ is generally said to be (1) in response to stressful external stimuli; (2) voluntary and nervously mediated; (3) supported by adaptive features that increase efficiency and simultaneously mediate the cost; and (4) morphologically delineated by a predictable breakage plane. It is estimated that this phenomenon has evolved independently nine different times across the animal kingdom, appearing in many different taxa, including vertebrate and invertebrate as well as aquatic and terrestrial animals. Marine invertebrates use this behaviour in a diversity of manners that have yet to be globally reviewed and critically examined. Here, published data from marine invertebrate taxa were used to explore instances of injury as an evolutionary driver of autotomy. Findings suggest that phyla (e.g. Echinodermata and Arthropoda) possibly experiencing high rates of injury (tissue damage or loss) are more likely to be able to perform autotomy. Additionally, this review looks at various morphological, physiological and environmental conditions that have either driven the evolution or maintained the behaviour of autotomy in marine invertebrates. Finally, the use of autotomic abilities in the development of more sustainable and less ecologically invasive fisheries is explored.
Variation in farming damselfish behaviour creates a competitive landscape of risk on coral reefs
Authors: Sheppard Catherine E. , Boström-Einarsson Lisa , Williams Gareth J. , Exton Dan A. , Keith Sally A.
Published: May 2024

Interspecific interactions are fundamental drivers of animal space use. Yet while non-consumptive effects of predation risk on prey space use are well-known, the risk of aggressive interactions on space use of competitors is largely unknown. We apply the landscape of risk framework to competition-driven space use for the first time, with the hypothesis that less aggressive competitors may alter their behaviour to avoid areas of high competitor density. Specifically, we test how aggressive risk from territorial algal-farming damselfishes can shape the spatial distribution of herbivore fish competitors. We found that only the most aggressive damselfish had fewer competitors in their surrounding area, demonstrating that individual-level behavioural variation can shape spatial distributions. In contradiction to the landscape of risk framework, abundances of farming damselfish and other fishes were positively associated. Our results suggest that reef fishes do not simply avoid areas of high damselfish abundance, but that spatial variation in aggressive behaviour, rather than of individuals, created a competitive landscape of risk. We emphasize the importance of individual-level behaviour in identifying patterns of space use and propose expanding the landscape of risk framework to non-predatory interactions to explore cascading behavioural responses to aggressive risk.
Disentangling developmental effects of play aspects in rat rough-and-tumble play
Authors: Liu Quanxiao , Radchenko Mariia , Špinka Marek
Published: May 2024

Animal play encompasses a variety of aspects, with kinematic and social aspects being particularly prevalent in mammalian play behaviour. While the developmental effects of play have been increasingly documented in recent decades, understanding the specific contributions of different play aspects remains crucial to understand the function and evolutionary benefit of animal play. In our study, developing male rats were exposed to rough-and-tumble play selectively reduced in either the kinematic or the social aspect. We then assessed the developmental effects of reduced play on their appraisal of standardized human–rat play (‘tickling’) by examining their emission of 50 kHz ultrasonic vocalizations (USVs). Using a deep learning framework, we efficiently classified five subtypes of these USVs across six behavioural states. Our results revealed that rats lacking the kinematic aspect in play emitted fewer USVs during tactile contacts by human and generally produced fewer USVs of positive valence compared with control rats. Rats lacking the social aspect did not differ from the control and the kinematically reduced group. These results indicate aspects of play have different developmental effects, underscoring the need for researchers to further disentangle how each aspect affects animals.
Robust spatial self-organization in crowds of asynchronous pedestrians
Authors: Tomaru Takenori , Nishiyama Yuta , Feliciani Claudio , Murakami Hisashi
Published: May 2024

Human crowds display various self-organized collective behaviours, such as the spontaneous formation of unidirectional lanes in bidirectional pedestrian flows. In addition, parts of pedestrians’ footsteps are known to be spontaneously synchronized in one-dimensional, single-file crowds. However, footstep synchronization in crowds with more freedom of movement remains unclear. We conducted experiments on bidirectional pedestrian flows (24 pedestrians in each group) and examined the relationship between collective footsteps and self-organized lane formation. Unlike in previous studies, pedestrians did not spontaneously synchronize their footsteps unless following external auditory cues. Moreover, footstep synchronization generated by external cues disturbed the flexibility of pedestrians’ lateral movements and increased the structural instability of spatial organization. These results imply that, without external cues, pedestrians marching out of step with each other can efficiently self-organize into robust structures. Understanding how asynchronous individuals contribute to ordered collective behaviour might bring innovative perspectives to research fields concerned with self-organizing systems.
Opening science to society: how to progress societal engagement into (open) science policies
Authors: Wehn U. , Ajates R. , Mandeville C. , Somerwill L. , Kragh G. , Haklay M.
Published: May 2024

A broad understanding of the aims and objectives of the international open science movement was recently adopted with the 2021 UNESCO Recommendation on Open Science, expanding the focus of open science to include scientific knowledge, infrastructures, knowledge systems and the open engagement of societal actors. In response, recent discussions on science policy practice are shifting to the implementation of open science via national policies. While policy instruments to support some aspects of open science are well-studied, guidance on the emerging ‘social’ aspects of open science has lagged, prompting UNESCO to generate guidance. In this paper, several authors of the UNESCO Open Science Toolkit guidance document on ‘Engaging societal actors in Open Science’ synthesize the scholarly underpinnings behind its recommendations. This work draws upon a targeted search from academic, policy, and grey literature in the fields of open science and community engagement, with a special focus on citizen science, to derive guidance on how to overcome barriers to the uptake of societal engagement approaches. The results present building blocks of what an enabling environment for the open engagement of societal actors could look like, identifying key considerations and reflecting on opportunities and challenges for progressing and evaluating sound open engagement of societal actors into regional & national (open) science policies.
A memory-theoretic account of citation propagation
Authors: Dougherty Michael R. , Illingworth David A. , Nguyen Rosalind
Published: May 2024

Despite the common assumption that citations are indicative of an article’s scientific merit, increasing evidence indicates that citation counts are largely driven by variables unrelated to quality. In this article, we treat people’s decisions of what to cite as an instance of memory retrieval and show that observed citation patterns are well accounted for by a model of memory. The proposed exposure model anticipates that small alterations in factors that affect people’s ability to retrieve to-be-cited articles from memory early in their life cycle are magnified over time and can lead to the emergence of highly cited papers. This effect occurs even when there is no variation in the starting point exposure probabilities (i.e. when assuming a level playing field where all articles are treated equally and of equal ‘quality’), and is exacerbated by natural variation in retrievability of articles due to encoding. We discuss the implications of the model within the context of research evaluation and hiring, tenure and promotion decisions.
The behavioural responses of bumblebees
Bombus terrestris
to simulated rain
Authors: Reeves Laura A. , Jarvis Ellie M. , Lawson David A. , Rands Sean A.
Published: May 2024

Bumblebee activity typically decreases during rainfall, putting them under the threat of the increased frequency of precipitation due to climate change. A novel rain machine was used within a flight arena to observe the behavioural responses of bumblebees (
Bombus terrestris
) to simulated rain at both a colony and individual level. During rainfall, a greater proportion of workers left the arena than entered, the opposite of which was seen during dry periods, implying that they compensate for their lack of activity when conditions improve. The proportion of workers flying and foraging decreased while resting increased in rain. This pattern reversed during dry periods, providing further evidence for compensatory activity. The increase in resting behaviour during rain is thought to evade the high energetic costs of flying while wet without unnecessarily returning to the nest. This effect was not repeated in individual time budgets, measured with lone workers, suggesting that the presence of conspecifics accelerates the decision of their behavioural response, perhaps via local enhancement. Bumblebees probably use social cues to strategize their energetic expenditure during precipitation, allowing them to compensate for the reduced foraging activity during rainfall when conditions improve.
Metabarcoding analysis provides insight into the link between prey and plant intake in a large alpine cat carnivore, the snow leopard
Authors: Yoshimura Hiroto , Hayakawa Takashi , Kikuchi Dale M. , Zhumabai Uulu Kubanychbek , Qi Huiyuan , Sugimoto Taro , Sharma Koustubh , Kinoshita Kodzue
Published: May 2024

Species of the family Felidae are thought to be obligate carnivores. However, detection of plants in their faeces raises questions about the role of plants in their diet. This is particularly true for the snow leopard (
Panthera uncia
). Our study aimed to comprehensively identify the prey and plants consumed by snow leopards. We applied DNA metabarcoding methods on 90 faecal samples of snow leopards collected in Kyrgyzstan, employing one vertebrate and four plant markers. We found that argali (
Ovis ammon
) was detected only from male snow leopards.
Myricaraia
sp. was the most consumed among 77 plant operational taxonomic units found in snow leopard samples. It frequently appeared in samples lacking any prey animal DNA, indicating that snow leopards might have consumed this plant especially when their digestive tracts were empty. We also observed differences in the patterns of plant consumption between male and female snow leopards. Our comprehensive overview of prey and plants detected in the faeces of snow leopards and other sympatric mammals will help in formulating hypotheses and guiding future research to understand the adaptive significance of plant-eating behaviour in felids. This knowledge supports the enhancement of their captive environments and the conservation planning of their natural habitats.
Long-term aquarium records delineate the synchronized spawning strategy of
Acropora
corals
Authors: Sakai Yusuke , Yamamoto Hiromi H. , Maruyama Shinichiro
Published: May 2024

Aligning spawning timing with seasonal environmental changes is critical for both terrestrial and aquatic organisms. However, mechanisms to regulate reproductive activity in response to environmental factors are not well understood, partly owing to the technical difficulty in maintaining detailed long-term observational data of the reproductive activities in the same population across years. In this study, we present an application of the aquarium system to examine the long-term spawning properties of corals. Spawning records over a 15-year period at the Okinawa Churaumi Aquarium revealed that the spawning timing of
Acropora
corals in aquarium tanks aligned well with that of wild corals from a neighbouring reef. Using the aquarium population as a model, we investigated the relationship between key environmental factors and the timing of the first and peak spawning dates of
Acropora
corals during a 15-year period. The results suggest that the spawning window of each spawning season is largely influenced by the water temperature and that the timing of peak spawning can be fine-tuned in response to environmental fluctuations. This behavioural feature can prevent synchronous spawning events during unfavourable environmental conditions and increase long-term reproductive reliability.
Unravelling Antibody-Induced Mechanical Stability of Antigen: Insights from Single-Molecule Studies
Authors: Chakraborty Soham , Pandit Shivam , Bhatt Madhu , Chowdhury Debojyoti , Chakrabarty Suman , Haldar Shubhasis
Published: May 2024

The intricate nature of antigen-antibody interactions plays a pivotal role in immunological responses. Despite the multitude of ligand-binding sites on antigens, the influence of antibodies on their mechanical stability remains elusive. This study elucidates the impact of IgM, the largest antibody isotype, on the mechanical stability of protein L, a bacterial superantigen, using single-molecule magnetic tweezers and steered molecular dynamics. Our findings reveal a concentration-dependent elevation in mechanical stability induced by IgM, as demonstrated by prolonged unfolding dwell times. Through steered molecular dynamics simulations, we elucidate the distinct mechanical responses of protein L binding interfaces at various IgM complex states, highlighting their synergistic effect on IgM dimer complex stability. Notably, this enhanced response stems from the altered unfolding pathway of protein L upon IgM interaction, providing significant insights into the generic mechanisms governing antibody-induced mechanical stability of antigenic substrates in physiological conditions, shedding light on the underlying folding dynamics and molecular mechanics of antigen-antibody interaction.
Local climate variability, phenology and morphological traits of the long distance migrants Savi’s warblerLocustella luscinioidesand Sedge warblerAcrocephalus schoenobaenusin reedbeds of a man-made wetland of SE Iberia
Authors: Peiró Ignacio García
Published: May 2024

As a consequence of climatic variability in the northern hemisphere, the Mediterranean region is experiencing the most pronounced effects of rising temperatures and decreasing precipitation. This has a multitude of effects on bird migration, with particular relevance to migratory passerines associated with wetlands, whose area has been in decline in this region since the last century. In order to relate phenology to morphology and climate in two species of trans-Saharan migrants closely associated with reedbeds, this study analysed the relationships between Savi’s warblersLocustella luscinioidesand Sedge warblersAcrocephalus schoenobaenusabundances, local climatology and morphological traits in an inland coastal artificial wetland in southeastern Iberia over a 12-year period. The climatic variability observed in this wetland was reflected in a negative trend between local temperatures and the year, and a positive trend with annual precipitation. This was confirmed in subsequent series. The abundance of Savi’s warbler increased adaptively with the year, while that of the Sedge warbler decreased non-adaptively, although neither change was statistically significant. A two-year delay was observed in the interannual phenology peak of the Savi’s warbler relative to the Sedge warbler. The monthly abundances of Savi’s warblers exhibited a significant positive correlation with intra-annual temperatures, explaining approximately half of the intra-annual phenology. No morphological trait could be identified as an explanatory factor for these trends, as no significant correlation with year was detected. Consequently, a coincidence with the morphological traits of both species associated with global climate change could not be established, which supports the hypothesis of migratory bird mismatch in the southeastern Iberia. In a future scenario in the eastern fringe of the Iberian Peninsula, an increase in the abundance of some trans-Saharan migrants, such as the Savi’s warbler, is to be expected as a consequence of climatic improvement, in particular rising temperatures. Further studies are required to ascertain whether this phenomenon occurs in other trans-Saharan migrants in other localities in the west.
Regeneration in the absence of canonical neoblasts in an early branching flatworm
Authors: Gąsiorowski Ludwik , Chai Chew , Rozanski Andrei , Purandare Gargi , Ficze Fruzsina , Mizi Athanasia , Wang Bo , Rink Jochen C.
Published: May 2024

The remarkable regenerative abilities of flatworms are closely linked to neoblasts – adult pluripotent stem cells that are the only division-competent cell type outside of the reproductive system. Although the presence of neoblast-like cells and whole-body regeneration in other animals has led to the idea that these features may represent the ancestral metazoan state, the evolutionary origin of both remains unclear. Here we show that the catenulidStenostomum brevipharyngium, a member of the earliest-branching flatworm lineage, lacks conventional neoblasts despite being capable of whole-body regeneration and asexual reproduction. Using a combination of single-nuclei transcriptomics, in situ gene expression analysis, and functional experiments, we find that cell divisions are not restricted to a single cell type and are associated with multiple fully differentiated somatic tissues. Furthermore, the cohort of germline multipotency genes, which are considered canonical neoblast markers, are not expressed in dividing cells, but in the germline instead, and we experimentally show that they are neither necessary for proliferation nor regeneration. Overall, our results challenge the notion that canonical neoblasts are necessary for flatworm regeneration and open up the possibility that neoblast-like cells may have evolved convergently in different animals, independent of their regenerative capacity.
Intra- and inter-chain contacts determine TCR specificity: applying protein co-evolution methods to TCRαβ pairing
Authors: Milighetti Martina , Nagano Yuta , Henderson James , Hershberg Uri , Tiffeau-Mayer Andreas , Bitbol Anne-Florence , Chain Benny
Published: May 2024

The six complementarity determining regions (CDRs) of the T cell receptor (TCR) form multiple contacts with cognate peptide and major histocompatibility complex, thus determining antigen specificity. However, the importance of contacts between the CDRs themselves remains poorly understood. With a systematic study of over 200 unique TCR structures, we identify consistent intra and inter-chain CDR contact zones. We hypothesise that these interactions may restrict TCRα/TCRβpairing within epitope-specific repertoires. Indeed, we show that the sequences of paired TCRαand TCRβare not independent within the repertoires of TCRs specific for most epitopes examined. We show that this sequence restriction can be quantified using a mutual information framework, can be learnt by co-evolution models without using a training set of known pairs and allowsde novopredictions of TCRα/TCRβpairing.
Systematic deconstruction of myeloid cell signaling in tuberculosis granulomas reveals IFN-γ, TGF-β, and time are associated with conserved myeloid diversity
Authors: Peters Joshua M. , Gideon Hannah P. , Hughes Travis K. , Gunnarson Cal , Maiello Pauline , Mugahid Douaa , Nyquist Sarah K. , Bromley Joshua D. , Blainey Paul C. , Junecko Beth F. , Nelson Molly L. , Lauffenburger Douglas A. , Lin Philana Ling , Flynn JoAnne L. , Shalek Alex K. , Fortune Sarah M. , Mattila Joshua T. , Bryson Bryan D.
Published: May 2024

Myeloid cells are key constituents of tuberculosis (TB) granulomas. They are the major target of pathogen infection and play central roles in pathogen control, antigen presentation, adaptive immune cell recruitment, and tissue homeostasis. However, the role of myeloid cells in TB has been studied largely throughex vivoexperimental approaches that do not capture the dynamic phenotypic and functional states of these cells in the disease environment. To address this gap, we used a combination of bulk and single-cell RNA sequencing (scRNA-seq), computational modeling, and imaging to define the molecular diversity of myeloid cells in granulomas fromMycobacterium tuberculosis-infected nonhuman primates. We observed an increase in myeloid cell diversity in granulomas compared to non-granulomatous lung tissue. This increased transcriptional diversity is defined by a continuum of macrophage differentiation-, metabolism-, and cytokine-regulated transcriptional programs.In vitroexperimental modeling of monocyte-to-macrophage differentiation in defined cytokine environments implicates differentiation time, IFN-γ, and TGF-β signaling as candidate drivers of macrophage diversity. We next examined the conservation of these populations across additional experimental models of Mtb infection and found myeloid cell subsets enriched across the TB disease spectrum. To further contextualize these responses, we constructed an atlas of myeloid cells across diverse human lung pathologies, finding myeloid cell subpopulations that were similar between TB and other lung pathologies as well as subpopulations that distinguish between diseases. Collectively, this study identifies points of integration between myeloid cell biology in TB granulomas and other lung diseases that can be used for defining the signals that instruct myeloid cell behavior in TB and other diseases, as well as advance myeloid cell-targeted therapies.
Inactivation of PRMT1 inhibits cardiac fibrosis via transcriptional regulation and perturbation of FBL activity in fibroblast-to-myofibroblast transition
Authors: Qian Jiang , Jackson-Weaver Olan , Shen Yudao , Jin Jian , Chen Yibu , Li Meng , Subramanyan Ram Kumar , Xu Jian
Published: May 2024

Cardiac fibrosis is a recognized cause of morbidity and mortality, yet effective pharmacological therapy that directly targets the fibrotic process remains lacking. Here we surveyed a group of methyltransferases known as protein arginine methyltransferases (PRMT) and demonstrated that PRMT1, which is the most highly expressed PRMT in the heart, was upregulated in activated cardiac fibroblasts, or myofibroblasts, in failing hearts. Deleting Prmt1 specifically in myofibroblasts or treating systemically with the PRMT1 inhibitor MS023 blocked myofibroblast formation, leading to a significant reduction in cardiac fibrosis and improvement in cardiac function in both acute and chronic heart injury models that manifest pervasive cardiac fibrosis. PRMT1 promoted the transition of cardiac fibroblasts to myofibroblasts by regulating transcription and epigenetic status. Additionally, PRMT1 methylated a key nucleolar protein fibrillarin 1 (FBL) and regulated nucleoli morphology and function during fibroblast fate transition. We further demonstrated a previously unrecognized requirement for FBL in myofibroblasts formation, by regulating myofibroblast gene induction and contractile force generation.
Discovery and characterization of dietary antigens in oral tolerance
Authors: Blum Jamie E. , Kong Ryan , Schulman E.A. , Chen Francis M. , Upadhyay Rabi , Romero-Meza Gabriela , Littman Dan R. , Fischbach Michael A. , Nagashima Kazuki , Sattely Elizabeth S.
Published: May 2024

Food antigens elicit immune tolerance through the action of regulatory T cells (Tregs) in the intestine. Although antigens that trigger common food allergies are known, the epitopes that mediate tolerance to most foods have not been described. Here, we identified murine T cell receptors specific for maize, wheat, and soy, and used expression cloning to de-orphan their cognate epitopes. All of the epitopes derive from seed storage proteins that are resistant to degradation and abundant in the edible portion of the plant. Multiple unrelated T cell clones were specific for an epitope at the C-terminus of 19 kDa alpha-zein, a protein from maize kernel. An MHC tetramer loaded with this antigen revealed that zein-specific T cells are predominantly Tregs localized to the intestine. These cells, which develop concurrently with weaning, constitute up to 2% of the peripheral Treg pool. Bulk and single-cell RNA sequencing revealed that these cells express higher levels of immunosuppressive markers and chemokines compared to other Tregs. These data suggest that immune tolerance to plant-derived foods is focused on a specific class of antigens with common features, and they reveal the functional properties of naturally occurring food-specific Tregs.
A zinc finger transcriptional repressor ZOS5-09 regulates rice grain size, starch and protein biosynthesis
Authors: Jaiswal Priya , Qasim Falah , Mahto Arunima , Vichitra Ankur , Tyagi Akhilesh K , Agarwal Pinky
Published: May 2024

Grain size is one of the key determinants of grain yield. Transcription factors form an important class of regulatory proteins that play crucial roles in regulating developmental responses. Our study focuses on a novel seed-preferential C2H2 zinc finger transcription factor, ZOS5-09 (LOC_Os05g38600) that plays an important role in regulating grain-related traits in rice. Rice plants with ZOS5-09 promoter::GUS construct showed its high expression in rice endosperm. In planta reporter effector assays and localization studies showed that ZOS5-09 is a nuclear-localized transcriptional repressor. It has a C-terminal NoRS (nucleolar retention signal). Ectopic and seed-preferential overexpression of ZOS5-09 resulted in lethality. Seed-preferential overexpression without NoRS was detrimental to grain filling. Rice plants with knock-down or CRISPR based knock-out of ZOS5-09 displayed reduced grain length and weight but increased grain width. Plant height, second leaf width, and panicle number were reduced and second leaf length were increased. The change in grain size was due to lower cell proliferation and increased cell size in the transverse direction due to down regulation of cell cycle related genes and increased expression of expansins. Decreased expression of ZOS5-09 also resulted in reduced total starch and protein content and higher endosperm chalkiness, thus, negatively affecting grain quality. ZOS5-09 directly regulated a seed storage protein encoding gene, GLU6 by binding to the zinc finger binding site in its promoter. It acted as a repressor by promoting deacetylation upon interaction with a histone deacetylase. In summary, our results indicate that optimum expression of ZOS5-09 is essential for proper rice grain development. Our study highlights the role of a transcriptional repressor in regulating rice grain traits and improves our understanding of the transcriptional regulatory networks affecting grain size.
Country-Wide Agent-Based Epidemiological Modeling Using 17 Million Individual-Level Microdata
Authors: Hesam Ahmad , Pijpers Frank P , Breitwieser Lukas , Hofstee Peter , Al-Ars Zaid
Published: May 2024

Calibration is a crucial step in developing agent-based models. Agent-based models are notorious for being difficult to calibrate as they can express various degrees of freedom when model parameters are unknown. Models that appear correctly calibrated to match macro-level observed data perform poorly when micro-level insights need to be inferred. As a result, policymakers cannot be certain that an agent-based model can accurately describe the dynamics of the real-world phenomena that the model tries to mimic. To begin tackling this challenge, we developed a methodology for an epidemiological use case at a full population scale of 17 million agents to observe the effects of using microlevel data for the calibration on the accuracy of the microlevel model outcomes. We show that by calibrating a model on national statistics, but using individual-level microdata, we can on average get 36% more accurate model outcomes on a subnational level. Our model implementation performs two orders of magnitude faster than prior work and allows efficient calibration on HPC computer systems.
Guidelines and Standard Frameworks for Artificial Intelligence in Medicine: A Systematic Review
Authors: Shiferaw Kirubel Biruk , Roloff Moritz , Balaur Irina , Welter Danielle , Waltemath Dagmar , Zeleke Atinkut Alamirrew
Published: May 2024

A growing volume of evidence marks the potential of Artificial Intelligence (AI) in medicine, in improving diagnostic accuracy, clinical decision support, risk/event prediction, drug discovery, and patient management. However, the continuous integration of AI into clinical settings requires the development of up-to-date and robust guidelines and standard frameworks that consider the evolving challenges of AI implementation in medicine. This review evaluates these guidelines’ quality and summarizes ethical frameworks, best practices, and recommendations.

The Appraisal of Guidelines, Research, and Evaluation (AGREE II) tool was used to assess the quality of guidelines based on six domains: scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability, and editorial independence. The protocol of this review including the eligibility criteria, the search strategy data extraction sheet and methods, was published prior to the actual review with International Registered Report Identifier (IRRID) of(DERR1-10.2196/47105).

The initial search resulted in 4,975 studies from two databases and five studies from manual search. Nine articles were selected for data extraction based on the eligibility criteria. We found that while guidelines generally excel in scope, purpose, and editorial independence, there is significant variability in applicability and the rigour of guideline development. Well-established initiatives such as DECIDE-AI, SPIRIT-AI, and CONSORT-AI have shown high quality, particularly in terms of stakeholder involvement. However, applicability remains a prominent challenge among the guidelines. We conclude that the reproducibility, ethical and environmental aspects of AI in medicine still need attention from both medical and AI communities. This review emphasizes the crucial need for high-quality guidelines and opens a new avenue in evaluating guidelines themselves. Our work highlights the need for working toward the development of integrated and comprehensive reporting guidelines that adhere to the principles of Findability, Accessibility, Interoperability and Reusability (FAIR). This alignment is essential for fostering a cultural shift towards transparency and open science, which are pivotal milestone for sustainable digital health research.
Feather aerodynamics suggest importance of lift and flow predictability over drag minimization
Authors: Alenius Frida , Revstedt Johan , Johansson L. Christoffer
Published: May 2024

Partly overlapping feathers form a large part of birds’ wing surfaces, but in many species the outermost feathers split, making each feather function as an independent wing. These feathers are complex structures that evolved to fulfil both aerodynamic and structural functions. Yet, relatively little is known about how the profile shape and microstructures of feathers impact aerodynamic performance. Here we determine, using fluid dynamic modelling, the aerodynamic capabilities of a section of the primary flight feather forming the leading edge of the split wing tip of a Jackdaw (Corvus monedula). Our findings demonstrate that the feather section exhibits a relatively high performance, with lift comparable to manmade aerofoils and plates with larger camber at higher Reynolds number. However, there is a drag penalty associated with the feather shaft. The model’s vortex shedding behaviour results in stable lift, with small fluctuations, compared to manmade aerofoils. Notably, the aerodynamic pitch torque around the shaft varies with angle of attack. This, when combined with the built-in pitch-up twist of the feather implies a passive pitch control mechanism for the feather. Taken together, our findings suggest evolutionary adaptations of the flow around the feather, which could be of interest when designing micro-air vehicles and wind turbines.
PITPβ promotes COPI vesicle fission through lipid transfer and membrane contact formation
Authors: Park Kunyou , Ju Sungeun , Choi Hyewon , Gao Peng , Bang Geul , Choi Jung Hoon , Jang Jiwon , Morris Andrew J. , Kang Byung-Ho , Hsu Victor W. , Park Seung-Yeol
Published: May 2024

Intracellular transport among organellar compartments occurs in two general ways, by membrane-bound carriers or membrane contacts. Specific circumstances that involve the coordination of these two modes of transport remain to be defined. Studying Coat Protein I (COPI) transport, we find that phosphatidylcholine with short acyl chains (sPC) is delivered through membrane contact from the endoplasmic reticulum (ER) to sites of COPI vesicle formation at the Golgi to support the fission stage. Phosphatidylinositol transfer protein beta (PITPβ) plays a key role in this process, with the elucidation of this role advancing a new understanding of how PITPβ acts, providing a mechanistic understanding of a specific circumstance when vesicular transport requires membrane contact, and contributing to a basic understanding of how transport carriers in a model intracellular pathway are formed.

Specific circumstances that membrane contact is needed for vesicular transport remain to be defined. We find that a critical lipid is delivered through membrane contact to support the fission stage of a model intracellular transport pathway.
Decoding Salience: A Functional Magnetic Resonance Imaging Investigation of Reward and Contextual Unexpectedness in Memory Encoding and Retrieval
Authors: Yi Yeo-Jin , Kreißl Michael C. , Speck Oliver , Düzel Emrah , Hämmerer Dorothea
Published: May 2024

The present study investigated the neuromodulatory substrates of salience processing and its impact on memory encoding and behaviour, with a specific focus on two distinct types of salience: reward and contextual unexpectedness. 46 participants performed a novel task paradigm modulating these two aspects independently and allowing for investigating their distinct and interactive effects on memory encoding while undergoing high resolution fMRI. By using advanced image processing techniques tailored to examine midbrain and brainstem nuclei with high precision, our study additionally aimed to elucidate differential activation patterns in subcortical nuclei in response to reward-associated and contextually unexpected stimuli, including distinct pathways involving in particular dopaminergic modulation. We observed a differential involvement of the ventral striatum, substantia nigra and caudate nucleus, as well as a functional specialisation within the subregions of the cingulate cortex for the two salience types. Moreover, distinct subregions within the substantia nigra in processing salience could be identified. Dorsal areas preferentially processed salience related to stimulus processing (of both reward and contextual unexpectedness) versus ventral areas were involved in salience-related memory encoding (for contextual unexpectedness only). These functional specialisations within SN are in line with different projection patterns of dorsal and ventral SN to brain areas supporting attention and memory, respectively. By disentangling stimulus processing and memory encoding related to two salience types, we hope to further consolidate our understanding of neuromodulatory structures' differential as well as interactive roles in modulating behavioural responses to salient events.
An orphan viral genome with controversial evolutionary status sheds light on a distinct lineage of flavi-like virus infecting plants
Authors: Xu Zhongtian , Zheng Luping , Gao Fangluan , Li Yiyuan , Sun Zongtao , Chen Jianping , Zhang Chuanxi , Li Junmin , Wang Xifeng
Published: May 2024

Advancements in high-throughput sequencing and associated bioinformatics methods have significantly expanded the RNA virus repertoire, including novel viruses with highly divergent genomes encoding ‘orphan’ proteins that apparently lack homologous sequences. This absence of homologs in routine sequence similarity search complicates their taxonomic classification and raises a fundamental question: Do these orphan viral genomes representbona fideviruses? In 2022, an orphan viral genome encoding a large polyprotein was identified in alfalfa (Medicago sativa) and named Snake River alfalfa virus (SRAV). Initially, SRAV was proposed to be within the flavi-like lineage of the familyFlaviviridae. Subsequently, another research group showed its common occurrence in alfalfa but challenged its taxonomic position, suggesting it belongs to the familyEndornaviridaerather thanFlaviviridae. In this study, a large-scale analysis of 77 publicly available small RNA datasets indicated that SRAV could be detected across various tissues and cultivars of alfalfa, and has a broad geographical distribution. Moreover, profiles of the SRAV-derived small interfering RNAs (vsiRNAs) exhibited typical characteristics of virus in plant hosts. Through comprehensive evolutionary analysis, we demonstrated that SRAV should be a positive single-stranded RNA (ssRNA) flavi-like virus that infects alfalfa, rather than a member of the double-stranded RNA (dsRNA) of the familyEndornaviridae. Our findings suggest that SRAV represents a unique class of plant-hosted flavi-like viruses with unusual genome organization and evolutionary status, differing from previously identified flavi-like viruses documented to infect plants. The latter shows a close evolutionary relationship to flavi-like viruses primarily found in plant-feeding invertebrates and lacks evidence of triggering host RNA interference (RNAi) responses so far. In summary, our study resolves the taxonomic controversy surrounding SRAV and suggests the potential existence of two distinct clades of plant-hosted flavi-like viruses with independent evolutionary origins. Furthermore, our research provides the first evidence of plant-hosted flavi-like viruses triggering the host’s RNAi antiviral response. The widespread occurrence of SRAV underscores its potential ecological significance in alfalfa, a crop of substantial economic importance.
Plant growth promotion inOryza sativabyBradyrhizobium sp.isolated from the rhizosphere ofAeschynomene indica
Authors: Samuel Karl Joseph , Rajeswari R.
Published: May 2024

Aeschynomene indicais traditionally used as green manure in Tamil Nadu, India, to cultivateOryza sativa. This plant containsBradyrhizobium sp. in its root and stem nodules as PGPR. In this work, we isolatedBradyrhizobium sp.from the root nodules ofA. indicausing a selective medium and used it as a biofertilizer forO. sativa. The isolated microorganism was confirmed by various biochemical tests of Bergey’s Manual. Plant growth activity was measured in terms of plant height, plant diameter, leaf width, leaf length, grain weight, soil nitrogen fixation and nutritional value of the grains. Growth promotion of isolatedBradyrhizobium sp. was compared with commercial NPK fertilizers and commercialRhizobiumliquid fertilizer. Plants treated withBradyrhizobium sp.provided a yield of 37.2 grams with average weight of 0.0182 g/grain while NPK treated plants had 38.4 g with average weight of 0.0175 g/grain. Total nitrogen fixed byBradyrhizobium sp.(192 kb/ha) is almost similar to that of commercial NPK fertilizer (196 kg/ha). The nutritional value of the grains produced byBradyrhizobiumtreatment (302 kcal) is higher than that of NPK fertilizer (286.12 kcal). Thus, free-livingBradyrhizobium sp.can be used as a biofertilizer for crops which does not have nodulation capability.