bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing the accuracy and safety of automated CO2 angiography to iodine angiography in peripheral arterial disease with chronic limb ischemia: a prospective cohort study
Authors: Afsharirad Ali , Javankiani Sepide , Noparast Morteza
Published: January 2025

Introduction:

Diagnostic angiography of peripheral arteries using carbon dioxide (CO2) is feasible in nearly all areas below the diaphragm. Using carbon dioxide as a contrast material in angiography provides the highest quality diagnostic results in the vascular segments above the knee. However, its diagnostic reliability decreases as it moves toward the distal side of the vessels below the knee. This study investigated the diagnostic accuracy and consistency between CO2 and iodine contrast angiography in patients with peripheral vascular disease (PVD) with chronic limb ischemia (CLI).

Methods:

The study prospectively enrolled 35 patients with PVD and CLI and performed both CO2 and iodine contrast angiography, comparing the results for each patient. Image quality, stenosis severity, and anatomical location were analyzed.

Results:

In this study, a total of 35 patients (19 male) with an average age of 56.91 ± 10.73 were examined. Among them, 13 patients (37.1%) had involvement in the femoral region, 8 patients (22.9%) in the popliteal region, 8 patients (22.9%) in the tibial region, and 6 patients (17.1%) in the foot region. CO2 angiography produced excellent image quality in 40% of cases, with good quality in another 25.7%. The quality decreased in the popliteal and foot regions. While stenosis assessment was comparable between the two methods in the femoral, popliteal, and tibial regions, there was a significant difference in the foot region. The sensitivity, specificity, positive predictive value, and negative predictive value of CO2 angiography were all 100% in the femoral and popliteal areas. However, these values were lower in the tibial and foot areas.

Discussion:

The study concluded that the use of CO2 angiography, particularly for vascular lesions above the popliteal cavity, is a valuable and safe method for peripheral vascular examination of the lower limbs. It can serve as an alternative to iodine contrast angiography, especially in patients with kidney failure.
Giant hemorrhagic omental cyst mimicking ascites in an 8-month-old infant: a case report
Authors: Neupane Narayan Prasad , Gyawali Balkrishna , Shah Abhishek Kumar , Kaini Manisha , Yadav Manish
Published: January 2025

Introduction:

Omental cysts are rare congenital lymphatic lesions in children, presenting as a palpable mass, abdominal distension, or acute abdomen. Complications include hemorrhage, rupture, and torsion. Diagnosis is challenging due to nonspecific symptoms, often requiring imaging. Surgical excision is the definitive treatment. This case highlights a unique presentation of a large hemorrhagic cyst, initially misdiagnosed as ascites.

Case presentation:

An 8-month-old male presented with irritability for 1 week, abdominal distension, poor feeding, and no stools for 3 days. Examination revealed fever, tachycardia, pale appearance, and distended abdomen with shifting dullness. Investigations showed severe anemia, leukocytosis, and complex ascites on imaging. Surgical exploration identified a 25 × 15 cm hemorrhagic omental cyst, resected alongside herniotomy for a left inguinal hernia. Histopathology confirmed cystic lymphangioma. Recovery was uneventful, with normal follow-up ultrasound at 6 months.

Discussion:

Omental cysts, rare in children, arise from ectopic lymphatic tissue and present variably as abdominal distension, pain, or intestinal obstruction. Misdiagnosed as ascites in this case, imaging often identifies cystic masses, though definitive diagnosis can be challenging. This infant’s severe anemia was unusual, requiring pre- and postoperative transfusions. Treatment typically involves complete excision; here, open resection was chosen due to the cyst’s size and hemorrhagic nature. This case underscores diagnostic challenges and emphasizes tailored management for rare abdominal cysts in children.

Conclusion:

This case highlights the diagnostic challenges of omental cysts in pediatric patients with atypical presentations. It underscores the importance of considering rare entities like omental cysts in acute abdomen cases and utilizing comprehensive diagnostic and surgical approaches.
Heart failure and microvascular dysfunction: an in-depth review of mechanisms, diagnostic strategies, and innovative therapies
Authors: Singh Ajeet , Ashraf Saad , Irfan Hamza , Venjhraj Fnu , Verma Amogh , Shaukat Ayesha , Tariq Muhammad Daoud , Hamza Hafiz Muhammad
Published: January 2025

Microvascular dysfunction (MVD) is increasingly recognized as a critical contributor to the pathogenesis of heart failure (HF), particularly in heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). Coronary microvascular dysfunction (CMD) significantly impacts HFpEF by reducing coronary flow reserve and myocardial perfusion reserve, leading to adverse outcomes such as myocardial ischemia, diastolic dysfunction, and increased risk of major cardiovascular events, including atrial fibrillation. In HFrEF, microvascular impairment is linked to heightened oxidative stress, reduced nitric oxide production, and activation of the renin-angiotensin-aldosterone system, further driving disease progression and contributing to poor prognosis. Advancements in diagnostic techniques, such as positron emission tomography, cardiac magnetic resonance imaging, and biomarker analysis, improve our ability to assess CMD in heart failure patients, enabling earlier diagnosis and risk stratification. Emerging therapies, including sodium-glucose cotransporter-2 inhibitors, angiotensin receptor-neprilysin inhibitors, and endothelial-targeted interventions, enhance microvascular function and improve patient outcomes. The role of personalized medicine is becoming increasingly important, as individualized therapeutic approaches tailored to patient-specific microvascular abnormalities are essential for optimizing treatment effectiveness. This review underscores the pivotal role of MVD in HF. It highlights the urgent need for innovative therapeutic strategies and diagnostic tools to address this complex condition and improve clinical outcomes for HF patients.
Examining the human-centred challenges of human–swarm interaction
Authors: Lyons Joseph B. , Capiola August , Adams Julie A. , Mator Janine D. , Cherry Erin , Barrera Kristen
Published: January 2025

We adopt a tripart approach in describing the human-centred challenges with human–swarm interaction. First, the results of large-N laboratory studies will be discussed which found evidence of trust biases (e.g. system-wide trust (SWT)), uncertainties regarding appropriate control strategies and timing, and inaccuracies of perceived swarm reliability. Second, the results of a small-N subject-matter expert study will be discussed, highlighting evidence for component-specific trust (CST) and will highlight concerns from expert operators regarding: understanding appropriate inputs for swarm control, transfer of control, general transparency for swarms including the need for understanding why errors might occur and concerns regarding the effects of command latency. Third, human-centred challenges from the use of swarms in the real world will be discussed. These challenges include lessons learned regarding human–swarm interfaces, the intense challenges of logistics when using swarms in the real world, and otherwise hidden challenges of using swarms for real-world scenarios such as the Defense Advanced Research Project Agency (DARPA) OFFensive Swarm-Enabled Tactics (OFFSET) programme and the use of swarms for monitoring operations for the Air Force Marathon. This article will close with a brief discussion of the opportunity space within human–swarm interaction if the research community is able to close the gap on these human-centred challenges.

This article is part of the theme issue ‘The road forward with swarm systems’.
Performance prediction of hub-based swarms
Authors: Jain Puneet , Dwivedi Chaitanya , Smith Nicholas , Goodrich Michael A.
Published: January 2025

There are powerful tools for modelling swarms that have strong spatial structures like flocks of birds, schools of fish and formations of drones, but relatively little work on developing formalisms for other swarm structures like hub-based colonies doing foraging, maintaining a nest or selecting a new nest site. We present a method for finding low-dimensional representations of swarm state for simulated homogeneous hub-based colonies solving the best-of-N problem. The embeddings are obtained from latent representations of convolution-based graph neural network architectures and have the property that swarm states which have similar performance have very similar embeddings. Such embeddings are used to classify swarm state into binned estimates of success probability and time to completion. We demonstrate how embeddings can be obtained in a sequence of experiments that progressively require less information, which suggests that the methods can be extended to larger swarms in more complicated environments.

This article is part of the theme issue ‘The road forward with swarm systems’.
On the ethical governance of swarm robotic systems in the real world
Authors: Winfield Alan F. T. , Swana Matimba , Ives Jonathan , Hauert Sabine
Published: January 2025

In this paper, we address the question: what practices would be required for the responsible design and operation of real-world swarm robotic systems? We argue that swarm robotic systems must be developed and operated within a framework of ethical governance. We will also explore the human factors surrounding the operation and management of swarm systems, advancing the view that human factors are no less important to swarm robots than social robots. Ethical governance must be anticipatory, and a powerful method for practical anticipatory governance is ethical risk assessment (ERA). As case studies, this paper includes four worked examples of ERAs for fictional but realistic real-world swarms. Although of key importance, ERA is not the only tool available to the responsible roboticist. We outline the supporting role of ethical principles, standards, and verification and validation. Given that real-world swarm robotic systems are likely to be deployed in diverse ecologies, we also ask: how can swarm robotic systems be sustainable? We bring all of these ideas together to describe the complete life cycle of swarm robotic systems, showing where and how the tools and interventions are applied within a framework of anticipatory ethical governance.

This article is part of the theme issue ‘The road forward with swarm systems’.
Linking the function of cis-acting RNA elements to coronavirus replication using interactomes
Authors: Yao Yueh-Chun , Yang Chun-Chun , Wang Meilin , Hsieh Feng-Cheng , Lin Ching-Hung , Hsu Hsuan-Wei , Lai Chien-Chen , Wang Wei-Chen , Kuo Cheng-Yu , Yang Cheng-Yao , Wu Hung-Yi
Published: January 2025

RNA structures that are functionally important are defined as cis-acting RNA elements because their functions cannot be compensated for in trans. The cis-acting RNA elements in the 3′ UTR of coronaviruses are important for replication; however, the mechanism linking the cis-acting RNA elements to their replication function remains to be established. In the present study, a comparison of the biological processes of the interactome and the replication efficiency between the 3′ UTR cis-acting RNA elements in coronaviruses, including severe acute respiratory syndrome coronavirus 2, suggests that (i) the biological processes, including translation, protein folding and protein stabilization, derived from the analysis of the cis-acting RNA element interactome and (ii) the architecture of the cis-acting RNA elements and their interactomes are highly correlated with coronavirus replication. In addition, alteration of the interactome using the compound 5-benzyloxygramine can cause reduced coronavirus replication, reinforcing the connection between cis-acting RNA elements and replication by interactome. Together, these results link cis-acting RNA elements to the coronavirus replication and establish a model to analyse the cis-acting RNA elements in the replication of RNA viruses by interactome.
Thermodynamic principles link in vitro transcription factor affinities to single-molecule chromatin states in cells
Authors: Schaepe Julia M. , Fries Torbjorn , Doughty Benjamin R. , Crocker Olivia J. , Hinks Michaela M. , Marklund Emil , Greenleaf William J.
Published: January 2025

The molecular details governing transcription factor (TF) binding and the formation of accessible chromatin are not yet quantitatively understood - including how sequence context modulates affinity, how TFs search DNA, the kinetics of TF occupancy, and how motif grammars coordinate binding. To resolve these questions for a human TF, erythroid Kruppel-like factor (eKLF/KLF1), we quantitatively compare, in high throughput, in vitro TF binding rates and affinities with in vivo single molecule TF and nucleosome occupancies across engineered DNA sequences. We find that 40-fold flanking sequence effects on affinity are consistent with distal flanks tuning TF search parameters and captured by a linear energy model. Motif recognition probability, rather than time in the bound state, drives affinity changes, and in vitro and in nuclei measurements exhibit consistent, minutes-long TF residence times. Finally, pairing in vitro biophysical parameters with thermodynamic models accurately predicts in vivo single-molecule chromatin states for unseen motif grammars.
Extracting Knowledge from Scientific Texts on Patient-Derived Cancer Models Using Large Language Models: Algorithm Development and Validation
Authors: Yao Jiarui , Perova Zinaida , Mandloi Tushar , Lewis Elizabeth , Parkinson Helen , Savova Guergana
Published: January 2025

Patient-derived cancer models (PDCMs) have emerged as indispensable tools in both cancer research and preclinical studies. The number of publications on PDCMs increased significantly in the last decade. Developments in Artificial Intelligence (AI), particularly Large Language Models (LLMs), hold promise for extracting knowledge from scientific texts at scale. This study investigates the use of LLM-based systems for automatically extracting PDCM-related entities from scientific texts. We evaluated two approaches: direct prompting and soft prompting using LLMs. For direct prompting, we manually create prompts to guide the LLMs to output PDCM-related entities from texts. The prompt consists of an instruction, definitions of entity types, gold examples and a query. We automatically train soft prompts – a novel line of research in this domain - as continuous vectors using machine learning approaches. Our experiments utilized state-of-the-art LLMs – proprietary GPT4-o and a series of open LLaMA3 family models. In our experiments, GPT4-o with direct prompts maintained competitive results. Our results demonstrate that soft prompting can effectively enhance the capabilities of smaller open LLMs, achieving results comparable to proprietary models. These findings highlight the potential of LLMs in domain-specific text extraction tasks and emphasize the importance of tailoring approaches to the task and model characteristics.
A parent-of-origin effect on embryonic telomere elongation determines telomere length inheritance
Authors: Jeon Hyuk-Joon , Levine Mia T. , Lampson Michael A.
Published: January 2025

Telomere length is inherited directly as a DNA sequence and as a classic quantitative trait controlled by many genes across the genome. Here, we show that neither paradigm fully accounts for telomere length inheritance, which also depends on a parent-of-origin effect on telomere elongation in the early embryo. By reciprocally crossing mouse strains with different telomere lengths, we find that telomeres elongate in hybrid embryos only when maternal telomeres are short and paternal telomeres are long. In the reciprocal cross, telomeres shorten. These differences in embryonic telomere elongation, which emerge before zygotic genome activation, predict adult telomere length. Moreover, when telomeres do elongate, we find molecular signatures of a recombination-based mechanism of telomere elongation, called the Alternative Lengthening of Telomeres (ALT) pathway, previously suggested to elongate telomeres in the pre-implantation embryo. We propose that ALT is triggered by a combination of genetic asymmetry in telomere length and epigenetic asymmetry between maternal and paternal chromosomes in the zygote. Our findings offer new insight into the complex interaction of genetic and epigenetic determinants of telomere length inheritance.
The application of metagenomics in the detection of arboviruses in mosquitoes (Diptera: Culicidade). A systematic review
Authors: David Everson dos Santos , Komninakis Shirley Vasconcelos , da Costa Fonseca Erique , da Silva Soledade Anne Caroline , Carmo dos Santos Karen , Picanço Souto Raimundo Nonato
Published: January 2025

Advances in deforestation and climate change directly imply changes in habits and the distribution of Culicidae across the globe, especially mosquitoes of medical importance and the main vectors of arboviruses. The viral metagenomics technique can be an important tool in characterizing the viral diversity present in mosquitoes. Thus, the aim was to identify evidence of the effectiveness of the viral metagenomics technique in detecting arboviruses in mosquitoes. This is a systematic review based on the PRISMA 2020 protocol. The research was carried out in five electronic databases: LILACS, PubMed, SciELO, Scopus and Web of Science, chosen to include studies published in health and interdisciplinary areas, as well as a complementary research on Google Scholar. Studies that used the viral metagenomics approach for the genomic evaluation of arboviruses found in mosquito samples were included, where the results demonstrated the presence of viral diversity and the identification of the genome of probable pathogenic viruses. The protocol was registered on the PROSPERO platform under the number CRD42024484713. 238 studies published in recent years were identified in the electronic databases. According to the inclusion/exclusion criteria, only 20 studies met the objectives for the systematic review. In all the studies, the viral metagenomics technique of genomic sequencing was applied to detect viruses, mainly those related to specific insect viruses, arboviruses, pathogenic viruses, animal viruses and plant viruses belonging to various viral families. Despite the challenges to be overcome in terms of the absence of reference sequences in genomic databases, the effectiveness of the metagenomics technique in characterizing the mosquito virome is clear from the studies, which broadens the understanding of viral diversity.
Single-cell transcriptional profiling reveals a novel RAB13+endothelial subpopulation and profibrotic mesenchymal cells in the aged human bone marrow
Authors: Cenzano Itziar , Cócera Miguel , Lopez-Perez Ana Rosa , Campos-Dopazo Lorea , Ruiz Javier , Sancho Ignacio , Martin-Uriz Patxi San , Sarvide Sarai , Aguirre-Ruiz Paula , Vilas-Zornoza Amaia , Ripalda-Cemborain Purificacion , Alignani Diego , Lopez Aitziber , Barrios Marta Miñana , Agreda Delia Quilez , Ye Jin , Lehmann Robert , Sudupe Laura , Abengozar-Muela Marta , Tamariz-Amador Luis-Esteban , Muiños-López Emma , Saez Borja , Tegner Jesper , Calvo Isabel A. , Gomez-Cabrero David , Prosper Felipe
Published: January 2025

The bone marrow (BM) microenvironment plays a crucial role in regulating hematopoiesis, yet the molecular and functional changes associated with aging in humans remain poorly understood. Using single-cell RNA sequencing (scRNA-seq), we uncovered transcriptional shifts in BM endothelial cells (EC) and mesenchymal stem cells (MSC) during aging. Our analysis revealed that aged sinusoidal EC adopt a prothrombotic, exhibit mitochondrial dysfunction, and have compromised vascular function. Additionally, we identified a unique arterial EC subset, present only in aged individuals, associated with transcriptional elongation and senescence processes and characterized byRAB13expression. MSC from aged subjects displayed an impaired matrix remodeling and epithelial-mesenchymal transition, driven partly by a subpopulation of THY1+profibrotic stromal cells absent in young subjects. Aged MSC were also characterized by an increased ATP-oxidative metabolism and reduced protein folding capacity. Finally, using immunofluorescent imaging and spatial transcriptomics, we confirmed the presence of RAB13+senescent EC in aged samples and revealed significant age-related changes in cell-cell communication within the BM niche. In summary, this work provides a comprehensive view of the molecular diversity, cellular interactions, and spatial organization of aged EC and MSC, offering novel insights and potential targets that could be exploited for preventing aged-associated changes in humans.
Morphology and distribution of a new scale mechanoreceptor type in olive-headed sea snakes (Hydrophis major)
Authors: Wagner Alizée , Johnson Chad , Ha Myoung Hoon , Sanders Kate L. , Collin Shaun P. , Crowe-Riddell Jenna M.
Published: January 2025

Snakes are known for their superb sensory specialisations but are not widely appreciated for their sense of touch despite emerging evidence of tactile specialisation among sea snakes. This is partly due to the challenges in quantifying such small and numerous scale mechanoreceptors or ‘scale sensilla’ across individuals. By using a novel application of gel-based 3D profilometry (GelSight scanner) in combination with scanning electron-and light microscopy, we comprehensively quantified the morphology and distribution of scale mechanoreceptors in a sea snake,Hydrophis major(Hydrophiinae), for the first time. We discovered a new type of scale mechanoreceptor distinguished by its larger size (43.65 ± 22.57 μm height) and asymmetrical peak shape, created by a thickening in the cornified outer layers of the epidermis. Asymmetrical peaks contain a dermal papilla with central cells, indicative of meissner-like corpuscles that underlie smooth dome-shaped mechanoreceptors (31.88 ± 19.03 μm height) typically found in both sea snakes, but is positioned slightly off centre from the tallest point of the asymmetrical peak. Smooth domes are concentrated anterior-posteriorly on the head with the highest densities on the rostrum and nasal scales (9.83 ± 1.88 and 5.24 ± 2.85 per mm², respectively). Asymmetrical peaks are rarer; detected only on the dorsal and lateral sides of the head and most common on the postocular scale (mean density 1.26 ± 0.72 per mm²). We suggest functional differences in mechanosensory capabilities: asymmetrical peaks may serve primarily proprioceptive purposes whereas smooth domes are used for hydrodynamic reception.
ScaleSC: A superfast and scalable single cell RNA-seq data analysis pipeline powered by GPU
Authors: Hu Wenxing , Zhang Haotian , Sun Yu H. , Cao Shaolong , Gagnon Jake , Ouyang Zhengyu , Moroishi Yuka , Zhang Baohong
Published: January 2025

The rise of large-scale single-cell RNA-seq data has introduced challenges in data processing due to its slow speed. Leveraging advancements in GPU computing ecosystems, such as CuPy, and building on Scanpy and rapids-singlecell package, we developed ScaleSC, a GPU-accelerated solution for single-cell data processing. ScaleSC delivers over a 20x speedup through GPU computing and significantly improves scalability, handling datasets of 10–40 million cells with over 1000 batches by overcoming the memory bottleneck on a single A100 card- far surpassing rapids-singlecell’s capacity of processing only 1 million cells without multi-GPU support. We also resolved discrepancies between GPU and CPU algorithm implementations to ensure consistency. In addition to core optimizations, we developed new advanced tools for marker gene identification, cluster merging, and more, with GPU-optimized implementations seamlessly integrated. Designed for ease of use, the ScaleSC package is compatible with Scanpy workflows, requiring minimal adaptation from users. The ScaleSC package (https://github.com/interactivereport/ScaleSC) promises significant benefits for the single-cell RNA-seq computational community.
Towards Multi-Brain Decoding in Autism: A Self-Supervised Learning Approach
Authors: Ranjabaran Ghazaleh , Moreau Quentin , Dubois Adrien , Dumas Guillaume
Published: January 2025

Abstract

This study introduces a self-supervised learning (SSL) approach to hyperscanning electroencephalography (EEG) data, targeting the identification of autism spectrum condition (ASC) during social interactions. Hyperscanning enables simultaneous recording of neural activity across interacting individuals, offering a novel path for studying brain-to-brain synchrony in ASC. Leveraging a large-scale, single-brain EEG dataset for SSL pretraining, we developed a multi-brain classification model fine-tuned with hyperscanning data from dyadic interactions involving ASC and neurotypical participants. The SSL model demonstrated superior performance (78.13% accuracy) compared to supervised baselines and logistic regression using spectral EEG biomarkers. These results underscore the efficacy of SSL in addressing the challenges of limited labeled data, enhancing EEG-based diagnostic tools for ASC, and advancing research in social neuroscience.
The heritability of migration behaviours in a wide-ranging ungulate
Authors: Bonar Maegwin , Wootton Eric , Anderson Charles R. , Wittemyer George , Northrup Joseph M. , Shafer Aaron B. A.
Published: January 2025

Migration behaviour is thought to be declining globally in the face of rapid human-mediated environmental change. While many species exhibit individual plasticity in their migratory behaviour, not all species demonstrate the level of plasticity necessary to adjust to novel conditions. Selection on heritable behaviours might therefore play an important role in the maintenance of migratory phenotypes for some species. Using GPS and genomic data from 242 individuals (256 animal-years) in a pedigree-free quantitative genetic approach, we estimated heritability, repeatability, and sources of environmental variation for migration traits in migrating mule deer (Odocoileus hemionus). We also estimated heritability of body size to ensure validity of our results. Heritability estimates of body size traits were comparable to the current estimates for ungulate body size. We found low heritability for broad patterns of migration timing, distance, and duration, but high heritability for movement rate along the migratory route. Our findings suggest that wild mule deer populations have the potential to respond to selection pressure generated by human activity or global environmental changes through microevolutionary changes in migration behaviours.

Significance Statement

Migration behaviour is critical for the reproduction and survival of a wide variety of taxa, yet there have been global declines in migrations in the face of rapid human-mediated environmental change. Despite our understanding that variation in migration behaviour has both genetic and environmental components, studies quantifying the sources of genetic variation contributing to migration phenotypes are lacking. Our study provides, to our knowledge, the first empirical evidence of heritability in a migration behaviour in ungulates. These results have implications for the evolution and maintenance of migration behaviours in natural populations.
Identity-by-descent mapping using multi-individual IBD with genome-wide multiple testing adjustment
Authors: Cai Ruoyi , Browning Sharon R.
Published: January 2025

We present an identity-by-descent mapping approach to test the association between genome-wide loci and complex traits. Our method evaluates whether levels of genetic similarities at specific genomic locations, captured by local relatedness matrices derived from multi-individual IBD sharing, are associated with phenotypic variation in complex traits. In addition, we propose an approach to adjust for multiple testing in genome-wide IBD mapping scans based on the correlation structure between test statistics across the genome. Through simulation studies, we demonstrate that our test has a well-controlled genome-wide type-I error rate and superior power to detect rare and untyped variants compared to standard single-variant tests. We applied our method to systolic blood pressure data from White British individuals in the UK Biobank.
Platelet mitochondrial transfer via extracellular vesicles modulates neutrophil phenotype and function
Authors: Allan Harriet E. , Dark Nicola , Vulliamy Paul , Crescente Marilena , Armstrong Paul C. , Ferreira Plinio , Warner Timothy D.
Published: January 2025

Platelet activation causes the release of extracellular vesicles, of which a small proportion contain respiratory competent mitochondria. Mitochondria are integral for energy production and in the regulation of apoptotic pathways. However, the existence of extracellular mitochondria highlights a potential new role in intercellular communication. We hypothesised that platelet extracellular vesicles could be taken up by circulatory cells and alter their function. In this work we demonstrate that platelet extracellular vesicles containing mitochondria interact with and are internalised by neutrophils. Flow cytometry revealed that this interaction promotes neutrophil surface receptor changes, indicative of enhanced neutrophil activation, adhesion and migration pathways. The internalisation of platelet mitochondria renders neutrophils unable to subsequently engulf bacteria, demonstrating reduced phagocytic capacity, but enhances the formation of neutrophil extracellular traps, both alone and in the presence of additional stimuli. Our findings show that platelet mitochondria released in extracellular vesicles can alter neutrophil activity and so may be important intercellular communicators and modulators of inflammatory and immune responses.
Phage defense and genome editing using novel retrons sourced from isolated environmental bacteria
Authors: Nakamura Kazuo L , Zhang Karen , Mestre Mario R , Rojas-Montero Matías , Shipman Seth L
Published: January 2025

Retrons are bacterial immune systems that protect a bacterial population against phages by killing infected hosts. Retrons typically comprise a reverse transcriptase, a template noncoding RNA that is partially reverse transcribed into RT-DNA, and a toxic effector. The reverse transcriptase, noncoding RNA, and RT-DNA complex sequester the toxic effector until triggered by phage infection, at which point the toxin is released to induce cell death. Due to their ability to produce single-stranded DNA in vivo, retrons have also been engineered to produce donor templates for genome editing in both prokaryotes and eukaryotes. However, the current repertoire of experimentally characterized retrons is limited, with most retrons sourced from clinical and laboratory strains of bacteria. To better understand retron biology and natural diversity, and to expand the current toolbox of retron-based genome editors, we developed a pipeline to isolate retrons and their bacterial hosts from a variety of environmental samples. Here, we present six of these novel retrons, each isolated from a different host bacterium. We characterize the full operon of these retrons and test their ability to defend against a panel ofE. coliphages. For two of these retrons, we further unravel their mechanism of defense by identifying the phage genes responsible for triggering abortive infection. Finally, we engineer these retrons for genome editing inE. coli, demonstrating their potential use in a biotechnological application.
An early surge of norepinephrine along brainstem pathways drives sensory-evoked awakening
Authors: Matosevich Noa , Regev Noa , Kimchy Uddi , Zelinger Noam , Kabaha Sina , Gabay Noam , Marmelshtein Amit , Nir Yuval
Published: January 2025

The locus coeruleus norepinephrine (LC-NE) system regulates arousal and awakening; however, it remains unclear whether the LC does this in a global or circuit specific manner. We hypothesized that sensory-evoked awakenings are predominantly regulated by specific LC-NE efferent pathways. Anatomical, physiological, and functional modularities of LC-NE pathways involving the mouse basal forebrain (BF) and pontine reticular nucleus (PRN) were tested. We found partial anatomical segregation between the LC->PRN and LC->BF circuits. Extracellular NE dynamics in BF and PRN exhibited distinct sound-evoked activation during sleep, including a fast sound-evoked NE peak specific to PRN. Causal optogenetic interrogation of LC efferent pathways, by retro-ChR2 activation or PdCO silencing of synapses in target regions, revealed a pivotal role for early LC->PRN activity in driving arousal and sound-evoked awakenings. Together, our results uncover a prominent role for early LC-NE PRN activity in connecting sensory and arousal pathways and establish LC heterogeneity in regulating arousal.

Abstract Figure
The Expression ofPax6Genes in an Eyeless Arachnid Suggests Their Ancestral Role in Arachnid Head Development
Authors: Joyce Isabella , Barnett Austen A.
Published: January 2025

Background

Many animal lineages utilizePax6transcription factors during eye development. Within Arthropoda, evidence suggests thatPax6genes are necessary for the specification of eyes in myriapods, crustaceans, and insects. However, recent data have argued thatPax6genes lack a role in the development of the eyes in Chelicerata (=arachnids, horseshoe crabs, and sea spiders). An alternative hypothesis argues that the absence ofPax6expression in developing chelicerate eyes could be explained by an earlier role for these genes in patterning eye precursor cells. The arachnid miteArchegozetes longisetosuslacks eyes, however it retains twoPax6paralogs in its genome. By leveraging these aspects ofA. longisetosus, we tested the hypothesis that ancestrally chelicerates did not usePax6genes to pattern their eyes but rather used them to pattern the central nervous system. We reasoned that if we observed comparable expression patterns ofPax6genes inA. longisetosusin comparison to those in arachnids that have retained eyes, then this would support the hypothesis thatPax6genes were not ancestrally used for eye specification in chelicerates.

Results

We followed the expression of canonical arthropod retinal determination genes to confirm thatA. longisetosusdoes not develop vestigial eyes. We found that the expression of thePax6paralogs was consistent with their roles in the development of the ocular region and central nervous system. By co- staining for these genes simultaneously with the conserved head patterning geneorthodenticle, we also observed early expression patterns of these genes in the protocerebrum of earlyA. longisetosusembryos that are comparable to those arachnids with embryonic eyes.

Conclusions

Our data provide support for the hypothesis thatPax6genes were not ancestrally used to pattern chelicerate eyes. The expression patterns ofPax6genes inA. longisetosuswere comparable to those of other arachnids that have eyes. This suggests that the retention ofPax6genes inA. longisetosusis due to their ancestral, non-eye patterning roles. Further supporting this hypothesis is our observation thatA. longisetosusdoes not pattern vestigial eyes. Lastly, our data suggests that thePax6genes, withorthodenticle, acted to specify the ancestral arachnid protocerebrum.
MITF regulates gene expression in middle tufted neurons and other projection neurons of the olfactory bulb
Authors: Mechmet Fatich , San José Alba Sabaté , Sigurðsson Snævar , Gautsson Ingvi , Steingrímsson Eiríkur , Petersen Pétur Henry
Published: January 2025

The microphthalmia-associated transcription factor (MITF) is a master transcription factor in melanocytes and plays equally important roles in mast cells. It is required for the generation, differentiation, and function of these cell types in vertebrates.Mitfis also expressed in the projection neurons of the olfactory bulb (OB), the mitral and tufted (M/T) cells. Loss ofMitfleads to neuronal hyperactivity in primary M/T cells but the general function ofMitfin neurons is unknown. Here, we identify putative MITF target genes in M/T cells, which show limited overlap with known targets in other cell types. These genes can be divided into two groups, those likely to inhibit neuronal activity and genes expressed specifically in a subclass of tufted cells, the middle tufted cells (mTCs). The mTCs are reduced in number in theMitfmutant OB, suggesting a role forMitfin the generation or survival of the mTCs and/or their function.

Significance statement

Identifying MITF target genes in the OB offers insights into its role in olfaction and the regulation of neuronal activity as well as uncovering its role in mTCs. MITF may play a role in various other processes in neurons.
Capturing dynamic phage-pathogen coevolution by clinical surveillance
Authors: Mathur Yamini , Boyd Caroline M. , Farnham Jeannette E. , Monir Md Mamun , Islam Mohammad Tarequl , Sultana Marzia , Ahmed Tahmeed , Alam Munirul , Seed Kimberley D.
Published: January 2025

Bacteria harness diverse defense systems that protect against phage predation1, many of which are encoded on horizontally transmitted mobile genetic elements (MGEs)2. In turn, phages evolve counter-defenses3, driving a dynamic arms race that remains underexplored in human disease contexts. For the diarrheal pathogenVibrio cholerae, a higher burden of its lytic phage, ICP1, in patient stool correlates with reduced disease severity4. However, direct molecular evidence of phage-driven selection of epidemicV. choleraehas not been demonstrated. Here, through clinical surveillance in cholera-endemic Bangladesh, we capture the acquisition of a parasitic anti-phage MGE, PLE11, that initiated a selective sweep coinciding with the largest cholera outbreak in recent records. PLE11 exhibited potent anti-phage activity against co-circulating ICP1, explaining its rapid and dominating emergence. We identify PLE11-encoded Rta as the novel defense responsible and provide evidence that Rta restricts phage tail assembly. Using experimental evolution, we predict phage counteradaptations against PLE11 and document the eventual emergence and selection of ICP1 that achieves a convergent evolutionary outcome. By probing how PLEs hijack phage structural proteins to drive their horizontal transmission while simultaneously restricting phage tail assembly, we discover that PLEs manipulate tail assembly to construct chimeric tails comprised of MGE and phage-encoded proteins. Collectively, our findings reveal the molecular basis of the natural selection of a globally significant pathogen and its virus in a clinically relevant context.
Revealing the hidden social structure of pigs with AI assisted automated monitoring data and social network analysis
Authors: Agha Saif , Psota Eric , Turner Simon P. , Lewis Craig R. G. , Steibel Juan P , Doeschl-Wilson Andrea
Published: January 2025

Social interactions of farm animals affect their performance, health and welfare. The recent advances in AI-automated monitoring technologies offer digital phenotypes, at low-cost, that record the animals in real-time. This proof-of-concept study addresses, for the first time, the hypothesis that applying social network analysis (SNA) on automated data could potentially facilitate the analysis of social structures of farm animals. Data was collected using automated recording systems that captured 2D camera images and videos of pigs in six pens (16–19 animals each) on a PIC breeding company farm (USA). The system provided real-time data, including ear-tag readings, elapsed time, posture (standing, lying, sitting), and XY coordinates of the shoulder and rump for each pig. Weighted SNA was performed, based on the proximity of “standing” animals, for two 3-day periods: the early growing period (first month after mixing) and the later period (60 days post-mixing). Group level degree, betweenness, and closeness centralization showed a significant increase from the early growing period to the later one (p<0.02), highlighting the pigś social dynamics over time. Largest clique size remained unchanged (p=0.28), but the number of maximal cliques significantly decreased from the early to late growing period (p=0.007). Individual SNA traits were stable over these periods, except for closeness centrality and clustering coefficient which significantly increased (p<0.00001). This study demonstrates that combining AI-assisted monitoring technologies with SNA offers an efficient, real-time approach to gain novel insights into animal social interactions. This approach can optimize on-farm management or breeding practices, leading to improved animal performance, health, and welfare.

Highlights

Social network analysis (SNA) applied to automated monitoring data provides novel insight into social interactions of pigs.

Group level SNA centralization traits highlighted pigs ‘social dynamics over time.

The stability of key individual SNA traits can be leveraged for breeding purposes.

AI-assisted monitoring combined with SNA help optimizing management practices on commercial farms.
Alterations of Task-based fMRI Topology Underlying Cognitive Flexibility and Stability in Schizophrenia
Authors: Sundermeier Maren , Standke Isabel , Schubotz Ricarda I. , Dannlowski Udo , Lencer Rebekka , Mecklenbrauck Falko , Trempler Ima , Zahedi Anoushiravan
Published: January 2025

Recently, it has been suggested that brain dysconnectivity in patients with schizophrenia contributes to the wide-ranging cognitive deficits that characterize the disorder. Graph theoretical analysis offers a unique method for studying how architectural alterations in large- scale brain networks may contribute to cognitive impairments in these patients. Implementing this technique, we analyzed the functional brain activity during a predictive switch-drift task from 21 patients with schizophrenia and 22 matched healthy controls. We specifically calculated task-based global graph measures for the functional networks that were activated during expected events, events requiring a flexible updating of predictions, and events that required the stabilization of predictions. By implementing Bayesian multivariate generalized linear models, we found functional network alterations during all event types, which indicated less centralized, less integrated, and simultaneously less segregated network topology in patients with schizophrenia compared to controls. In addition, the rate of correctly detected switches, requiring flexible updating of internal models, predicted global graph measures differently for patients compared to controls. In particular, lower cognitive flexibility in patients was associated with reduced integration of functional networks. Overall, the results indicate an adaptation of network topologies, resulting in less optimal network organization in patients with schizophrenia compared to healthy controls.
Roles Played by Enhancer of Split Transcription Factors inDrosophilaR7 Photoreceptor Specification
Authors: Ronald A. Arias , Yannis E. Mavromatakis , Tomlinson Andrew
Published: January 2025

When a cell receives multiple developmental signals simultaneously, the intracellular transduction pathways triggered by those signals are coincidentally active. How then, do the cells decode the information contained within those multiple active pathways to derive a precise developmental directive? The specification of the Drosophila R7 photoreceptor is classic model system for investigating such questions. The R7 fate is specified by the combined actions of the of the Notch (N) and receptor tyrosine kinase (RTK) signaling pathways. The two pathways cross-communicate in an integrative mechanism but also supply information independently of each other. Collectively, this information is summed to provide an unambiguous directive for the R7 fate. Our goal is to understand these mechanisms. Here, we examine how N activity represses transcription of thephyllopodgene in the process of information integration with the RTK pathway, and how it represses expression of theseven-upgene in an independent mechanism needed for R7 fate. We describe how N activity achieves these transcriptional repressions, and identify Enhancer of Split transcription factors as the mediators of those actions.

Summary Statement

This work examines the role played by Enhancer of Split transcription factors in mediating N signals in Drosophila R7 photoreceptor specification.
Early Universe Hypercharge Breaking and Neutrino Mass Generation
Authors: López-Zurdo S. , Lozano-Onrubia A. , Merlo L. , No J. M.
Published: January 2025

We show that the conditions allowing for a spontaneous breaking of the U(1)Y hypercharge gauge symmetry of the standard model (SM) in the early Universe are generically present in extensions of the SM addressing the generation of light neutrino masses via radiative contributions. In such scenarios, the breaking of (hyper)charge at high temperatures yields new possibilities for explaining the observed matter-antimatter asymmetry of the Universe. Considering for concreteness the Zee-Babu radiative neutrino mass generation model, we show that a period of hypercharge breaking prior to the electroweak phase transition could allow for successful baryogenesis via a nonconventional leptogenesis mechanism, based on the presence of charge-breaking masses for the SM leptons in the early Universe.

Published by the American Physical Society
2025
Firing propagation in empirical cognitive networks of human brain
Authors: Chen Dehua , Gao Ruohua , Yang Zhiyin , Huo Siyu , Liu Zonghua
Published: January 2025

Understanding the physical mechanisms of brain functions has always been a challenging problem in the fields of nonlinear dynamics and network science. A promising approach to address this problem is by studying signal propagation on brain cognitive networks. So far, in the context of signal propagation, some progress has been achieved on complex networks, especially on the network, but little attention has been paid to the empirical cognitive networks of the human brain, which are the networks responsible for cognitive tasks. Here we study how neural firings are propagated in the empirical cognitive networks of human brain. We find that the firing propagation can be seriously influenced by both the global topology of the network and the local topology of the source node. There is an optimal range of coupling strength related to synchronization for each source node, and multiple source nodes favor firing propagation. Further, we show that peripheral nodes of a network may have stronger ability of firing propagation than hub nodes. Interestingly, a remote firing propagation is observed, where firings are not propagated in a sequential rule, but propagated to farther distant nodes without the firings of intermediate nodes. A detailed theoretical analysis is provided to explain both the firing propagation and remote firing propagation.

Published by the American Physical Society
2025