bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying the success of prey crypsis, aposematism and evasiveness in avoiding predators’ attack
Authors: Linke Daniel , Mejia Jacqueline Hernandez , Navarro Valery N. P. Eche , Gohil Prapti , García César Ramírez , Salinas Letty , Elias Marianne , Matos-Maraví Pável 
Published: November 2024

AbstractAntipredator defences typically act at distinct stages of the predation sequence—encounter, identification, approach, and subjugation. However, their effectiveness has rarely been quantified and compared simultaneously in wild predator-prey systems. We conducted a study in Peru, where we installed aviaries at two localities and recorded the responses of wild avian predators to three types of antipredator defences—crypsis, aposematism, and evasiveness—expressed by three butterfly species. The study included both immature and adult birds from insectivorous species in forest and urban environments. We tested the theoretical expectations that cryptic butterflies (Nymphalidae: Euptychiina) were rarely detected, aposematicHeliconius(Nymphalidae: Heliconiinae) were often sighted but seldom attacked, and evasiveSpicauda(Hesperiidae: Eudaminae) were frequently detected and attacked but evaded capture at higher rates. Despite these distinct defensive strategies, mortality rates among prey types were largely similar, but predator life stage strongly influenced defence effectiveness. Immature birds were more likely to attackHeliconius, possibly reflecting a lack of learned avoidance for aposematic signals. Additionally, predator family influenced predation patterns, with more skilled insectivores (e.g., Vireonidae) showing higher capture success against defended prey. These findings illuminate the evolutionary pressures that shape predator behaviour and prey defences in tropical ecosystems, where high predator diversity possibly maintains the coexistence of multiple defensive strategies. The observed similar mortality rates underscore the adaptive value of these defences, as they collectively distribute the total predation pressure across prey species.
An ultra-conserved ARF-DNA interface underlies auxin-triggered transcriptional response
Authors: Rienstra Juriaan , Carrillo Carrasco Polet Vanessa , Hernandez Garcia Jorge , Weijers Dolf 
Published: November 2024

AbstractAuxin Response Factor (ARF) plant transcription factors are the key effectors in auxin signalling. Their DNA-Binding Domain (DBD) contains a B3 domain that allows base-specific interactions with Auxin Response Elements (AuxREs) in DNA target sites. Land plants encode three phylogenetically distinct ARF classes: the closely related A- and B-classes have overlapping DNA binding properties, contrasting with the different DNA-binding properties of the divergent C-class ARFs. ARF DNA-binding divergence likely occurred early in the evolution of the gene family, but the molecular determinants underlying it remain unclear. Here, we show that the B3 DNA-binding residues are deeply conserved in ARFs, and variability within these is only present in tracheophytes, correlating with greatly expanded ARF families. Using the liverwortMarchantia polymorpha, we confirm the essential role of conserved DNA-contacting residues for ARF function. We further show that ARF B3-AuxRE interfaces are not mutation-tolerant, suggesting low evolvability that has led to the ultra-conservation of the B3-DNA interface between ARF classes. Our data support the almost complete interchangeability between A/B-class ARF B3 by performing interspecies domain swaps, even between lineages that diverged over half a billion years ago. Our analysis further suggests that DNA-binding specificity diverged early during ARF evolution in a common streptophyte ancestor, followed by strong selection as part of a competition-based auxin response systemSignificance StatementAuxin response evolved nearly half a billion years ago in the earliest land plants. Auxin response is mediated by a family of DNA-binding ARF transcription factors. It has been unclear if and how the ARF family has evolved. In this paper, the authors show that the central protein-DNA interface that defines the genes that are under auxin control has remained essentially unchanged throughout auxin response evolution, explaining how auxin has become a dominant signal controlling growth and development in all land plants.
Synonymous codon usage defines functional gene families
Authors: Ghanegolmohammadi Farzan , Ohnuki Shinsuke , Byrne Shane , Begley Thomas J. , Dedon Peter C. 
Published: November 2024

AbstractBackgroundThe degeneracy of the genetic code is increasingly recognized for roles in regulating translation rate, protein folding, and cell response. However, the functional genomics of codon usage patterns remains poorly defined. We previously showed that prokaryotic and eukaryotic cells respond to individual stresses by uniquely reprogramming the tRNA pool and the dozens of tRNA modifications comprising the tRNA epitranscriptome to cause selective translation of mRNAs from codon-biased genes. Here, we systematically defined distinct values of codon bias in theSaccharomyces cerevisiaegenome by modeling isoacceptor codon distributions using a new statistical toolbox – analysis of synonymous codon signatures (ASCS).ResultsApplication of ASCS to theS. cerevisiaegenome revealed linear relationships between patterns of codon bias and gene function using canonical correlation analysis. By mapping codon-biased open reading frames (ORFs) onto a functional network of Gene Ontology (GO) categories, we identified 115 gene families distinguished by unique codon usage signatures. The codon usage patterns were found to strongly predict functional clusters of genes, such as translational machinery, transcription, and metabolic processes.ConclusionsThe ASCS-derived model of codon usage patterns inS. cerevisiaereveals functional codon bias signatures and captures more biologically meaningful information when compared to other codon analytical approaches.
Selecting cacao clones with high productivity potential and tolerance to Black Pod Rot (BPR) and Frosty Pod Rot (FPR)
Authors: López Marlon Enrique , Ramírez Oscar Arnulfo , Dubón Aroldo , Díaz Javier 
Published: November 2024

ABSTRACTCacao (Theobroma cacao) is affected annually by Frosty Pod Rot (FPR) (Moniliopthora roreri) and Black Pod Rot (BPR) (Phytophthorasp). The loss caused by both diseases is threatening cacao production worldwide. Therefore, cacao breeding programs focus on developing new cacao clones with high productivity potential and disease resistance. However, this challenge is not easy to achieve due to the long time required for selection, the influence of environmental conditions on the severity of the disease, and the avoidance of chemical control of diseases. Therefore, genetic resistance should be the best option for selecting and releasing new cacao clones to the farmers. In this study, 40 cacao clones, 20 from CATIE and 20 from FHIA breeding programs were evaluated from 2013 to 2017. Three criteria were used to select clones: Yield, Percentage Disease Pod (PDP), and Disease and Production Index (DPI). Results indicated that depending on the cacao breeding program objectives, it is possible to use those criteria to select new cacao clones that are highly productive and resistant to diseases because cacao clones with high productivity are not always the most resistant to diseases and vice versa; however, a combination of both criteria can be used to select cacao clones with high productivity potential and resistance to FPR and BPR.
Electroconvulsive therapy generates a postictal wave of spreading depolarization in mice and humans
Authors: Rosenthal Zachary P , Majeski Joseph B. , Somarowthu Ala , Quinn Davin K , Lindquist Britta E. , Putt Mary E. , Karaj Antoneta , Favilla Chris G , Baker Wesley B. , Hosseini Golkoo , Rodriguez Jenny P , Cristancho Mario A , Sheline Yvette I , Shuttleworth C. William , Abbott Christopher C. , Yodh Arjun G , Goldberg Ethan M 
Published: November 2024

AbstractElectroconvulsive therapy (ECT) is a fast-acting, highly effective, and safe treatment for medication-resistant depression. Historically, the clinical benefits of ECT have been attributed to generating a controlled seizure; however, the underlying neurobiology is understudied and unresolved. Using optical neuroimaging of neural activity and hemodynamics in a mouse model of ECT, we demonstrated that a second brain event follows seizure: cortical spreading depolarization (CSD). We found that ECT pulse parameters and electrode configuration directly shaped the wave dynamics of seizure and subsequent CSD. To translate these findings to human patients, we used non-invasive diffuse optical monitoring of cerebral blood flow and oxygenation during routine ECT treatments. We observed that human brains reliably generate hyperemic waves after ECT seizure which are highly consistent with CSD. These results challenge a long-held assumption that seizure is the primary outcome of ECT and point to new opportunities for optimizing ECT stimulation parameters and treatment outcomes.
High-throughput, multiplexed quantification, and sorting of single EVs at single-molecule level
Authors: Park Juhwan , Feng Michelle , Yang Jingbo , Shen Hanfei , Qin Zhiyuan , Guo Wei , Issadore David A. 
Published: November 2024

AbstractWe have developed a platform for the high-throughput, multiplexed, and ultra-sensitive profiling of individual extracellular vesicles (EVs) directly in plasma, which we call BDEVS - AgaroseBead-basedDigital Single Molecule-SingleEV Sorting. Unlike conventional approaches, BDEVS achieves single molecule sensitivity and moderate multiplexing (demonstrated 3-plex) without sacrificing the throughput (processing ten thousand of EVs per minute) necessary to resolve EVs directly in human plasma. Our platform integrates rolling circle amplification (RCA) of EV surface proteins, which are cleaved from single EVs, and amplified within agarose droplets, followed by flow cytometry-based readout and sorting, overcoming steric hindrance, non-specific binding, and the lack of quantitation of multiple proteins on EVs that have plagued earlier approaches. We evaluated the analytical capabilities of BDEVS through head-to-head comparison with gold-standard technologies, and demonstrated a ∼100x improvement in the limit of detection of EV subpopulations. We demonstrate the high throughput (∼100k beads / minute) profiling of individual EVs for key immune markers PD-L1, CD155, and the melanoma tumor marker TYRP-1, and showed that BDEVS can precisely quantify and sort EVs, offering unprecedented resolution for analyzing tumor-immune interactions and detecting rare EV subpopulations in complex clinical specimens. We demonstrate BDEVS’s potential as a transformative tool for EV-based diagnostics and therapeutic monitoring in the context of cancer immunology by analyzing plasma samples from patients with melanoma, where EV heterogeneity plays a critical role in disease progression and response to therapy.Graphical Abstract
Spatiotemporal regulation by downstream genes ofProk2in olfactory system: from development to function
Authors: Kim Bo-Ra , Rha Min-Seok , Cho Hyung-Ju , Yoon Joo-Heon , Kim Chang-Hoon 
Published: November 2024

AbstractOlfaction is important for the quality of life; however, in Kallmann syndrome (KS), defective development results in olfactory dysfunction. The mechanism underlying olfactory development, especially in the olfactory epithelium (OE), which detects olfactory signals, remains unclear. Mutations inPROK2, which encodes prokineticin-2, occur in approximately 9% of the KS patients with olfactory defects. In this study, we examined olfactory function and analyzed the causes of olfactory dysfunction based on spatiotemporal development and gene expression changes inProk2knockout (KO) model mice with KS. AdultProk2KO mice exhibited reduced ability to detect olfactory signals. Maturation of olfactory sensory neurons (OSNs) in the OE and formation of glomeruli in the olfactory bulb (OB) in adultProk2KO mice were disrupted, thus causing olfactory dysfunction. Molecular analysis ofProk2KO mice during embryonic development revealed abnormal development of OB layers and reduced differentiation to mature OSNs in the OE, which caused defects in the entire olfactory system. Downstream signaling genes ofProk2, including intermediate filament genes and genes expressed in the putative OB, mediated olfactory system organization. Our findings reveal the role ofProk2in olfactory system organization, providing insights into the mechanisms through which olfactory development defects translate to olfactory function.
Building capacity among caregivers for managing children with Type 1 Diabetes Mellitus through a structured Interprofessional training program
Authors: Juhi Ayesha , Valladath Saleena Ummer , Mondal Himel , Kumar Rajan , Bhattacharya Sangita , Nath Santanu , Dhanvijay Anupkumar , Prabhu Mukhayprana 
Published: November 2024

ABSTRACTBackgroundEffective management of type 1 diabetes mellitus (T1DM) in children necessitates not only medical care but also substantial involvement from caregivers, who often encounter psychological, financial, and emotional challenges. This study aimed to develop and evaluate a structured educational program for caregivers of children with T1DM, facilitated by an interprofessional team.MethodsThis mixed-method study, conducted from May 15 to August 15, 2023, comprised two parts. First, a structured educational module was developed based on a needs assessment from semi-structured interviews with 20 caregivers. The module was created in English, Hindi, and Khortha (the local language of Deoghar, Jharkhand, India) and validated by a panel of 10 experts (CVI = 0.83). It was delivered using audio-visual aids, live demonstrations, posters, and booklets. The program’s effectiveness was evaluated through a pre-post-test questionnaire.ResultsThe interviews revealed themes such as misunderstandings of treatment plans, distress from frequent insulin administration, fear of glucose monitoring, financial burdens, and psychological stress. Data from 68 of the 75 caregivers who participated in the educational program were analyzed. The Wilcoxon signed-rank test indicated a significant improvement in caregiver knowledge and management practices (P < 0.001), with a large effect size (Cohen’s d = 3.2).ConclusionThis study demonstrates that structured educational interventions can significantly enhance caregivers’ knowledge and practices in managing T1DM. Multidisciplinary education and support are crucial for addressing the emotional and financial burdens caregivers face, ultimately improving the well-being of both caregivers and children.
A New Labelling Method of99mTc-PSMA-HBED-CC
Authors: Phromphao Benchamat , Shiratori Shuichi 
Published: November 2024

AbstractObjective68Ga-PSMA-HBED-CC (68Ga-PSMA-11) was approved by the US FDA as the first PSMA-targeted PET imaging drug for patients with prostate cancer. However, the utility of68Ga-PSMA-HBED-CC may be limited due to PET/CT or PET/MR accessibility and68GaCl3availability produced from68Ge/68Ga generator or cyclotron. Thus, in-house preparation of99mTc-PSMA-HBED-CC was developed as an alternative to68Ga-PSMA-HBED-CC to be ubiquitous and affordable in the worldwide population.MethodsA solution of99mTc-pertechnetate was added to PSMA-HBED-CC and 4% SnCl2·2H2O in a 10 mL sterile vial. The mixture was heated at 100°C for 15 minutes and then allowed to cool to room temperature. Labeling conditions were optimized to maximize the radiochemical yield of99mTc-PSMA-HBED-CC. The chelation completeness was monitored using instant thin layer chromatography (iTLC), and the stability of99mTc-PSMA-HBED-CC was subsequently evaluated.ResultsThe radiolabeling of99mTc-PSMA-HBED-CC was succeeded using the appropriate amount of 10 µg PSMA-HBED-CC 3 µg SnCl2·2H2O and99mTc-pertechnetate 370 MBq at 100 °C for 15 mins, yielded the best result in high radiochemical yield (71.49 ± 2.42%), radiochemical purity (98.29 ± 2.65%), specific activity of 37.84 ± 1.47 GBq/µmol.99mTc-PSMA-HBED-CC is stable with radiochemical purity of more than 95% within 4 hrs at room temperature.ConclusionA new labelling method of99mTc-PSMA-HBED-CC was developed. Quality control parameters of99mTc-PSMA-HBED-CC met the criteria in accordance with the European Pharmacopoeia.
Structure and evolution of Photosystem I in the early-branching cyanobacteriumAnthocerotibacter panamensis
Authors: Jiang Han-Wei , Gisriel Christopher J. , Cardona Tanai , Flesher David A. , Brudvig Gary W. , Ho Ming-Yang 
Published: November 2024

AbstractThylakoid-free cyanobacteria are thought to preserve ancestral traits of early-evolving organisms capable of oxygenic photosynthesis. However, and until recently, photosynthesis studies in thylakoid-free cyanobacteria were only possible in the model strain Gloeobacter violaceus. Here, we report the isolation, biochemical characterization, cryo-EM structure, and phylogenetic analysis of photosystem I from a newly-discovered thylakoid-free cyanobacterium, Anthocerotibacter panamensis, a distant relative of the genus Gloeobacter. We find that A. panamensis photosystem I exhibits a distinct carotenoid composition and has one conserved low-energy chlorophyll site, which was lost in G. violaceus. These features explain the capacity of A. panamensis to grow under high light intensity, unlike other Gloeobacteria. Furthermore, we find that, while at the sequence level photosystem I in thylakoid-free cyanobacteria has changed to a degree comparable to that of other strains, its subunit composition and oligomeric form might be identical to that of the most recent common ancestor of cyanobacteria.
A study protocol for an international registry observational study evaluating clinical outcomes of transcatheter versus standard surgical mitral valve operation for secondary mitral regurgitation: the TEERMISO study
Authors: Nappi Francesco , Avtaar Singh Sanjeet Singh , Salsano Antonio , Spadaccio Cristiano , Shingu Yasushige , Wakasa Satoru , Fiore Antonio 
Published: November 2024

AbstractBackgroundSecondary mitral regurgitation (SMR) is a condition affecting the left ventricle (LV) rather than the mitral valve (MV). If the mitral valve (MV) remains structurally unchanged, enlargement of the left ventricle (LV) or impairment of the papillary muscles (PM) can occur. Several mechanical interventions are available to dictate the resolution of MR. However, there is a lack of robust data to compare mitral valve replacement, mitral valve repair (including subvalvular repair), and transcatheter mitral valve procedures (TMVp). This study aims to compare the effectiveness and clinical outcomes of TMVp using the edge-to-edge mitral valve repair (TEER) technique and standard surgical mitral valve procedures (S-SMVp) in patients with SMR.Methods and analysisFive cardiac surgery centres from four European countries and Japan have collaborated to create a multicentre observational registry (TEERMISO). The registry will enrol consecutive patients who underwent mechanical intervention for SMR between January 2007 and December 2023. The investigators assessed the difference between replacement and repair for both the standard surgical approach and the transcatheter procedure. The main clinical outcome will be the degree of LV remodelling as assessed by the Left Ventricular End-Diastolic Volume Index at 10 years. The study will measure several secondary endpoints, including all-cause mortality as the primary endpoint, followed by functional status, hospitalisation, neurocognition, physiological measures (echocardiographic assessment), adverse events and reoperation.Ethics and disseminationEthics approval was obtained in Montpellier University Hospital on 24 May 2022 (Institutional Review Board (IRB) Approval Number: IRB-MTP_2022_05_202201143). The results of the main study and each sub-analysis will be submitted for publication in a peer-reviewed journal. ClinicalTrials.gov ID:NCT05090540; IRB ID: 202201143. (Supplementary material)Strengths and limitations of this studyThis study will be conducted as a large international registry concerning interventions to correct secondary mitral regurgitation; it will provide clinicians important information about transcatheter and surgical techniques in the specific field of the secondary mitral regurgitation.The primary outcome will offer opportunity to better predict left ventricular remodeling after the procedures.The secondary outcomes of this study will offer opportunity to provide important information abut survivalThe retrospective nature of the study is a limitation to the study design.
The clots removed from ischaemic stroke patients by mechanical thrombectomy are amyloid in nature
Authors: Grixti Justine M. , Chandran Arun , Pretorius Jan-Hendrik , Walker Melanie , Sekhar Alakendu , Pretorius Etheresia , Kell Douglas B 
Published: November 2024

AbstractIschemic stroke due to large vessel occlusion results from the blockage of a major cerebral artery by a clot; however, the origins and molecular composition of these clots remain poorly understood. Mechanical thrombectomy has become a standard treatment to remove obstructive clots, providing a unique opportunity to analyze their properties. We previously demonstrated that blood can clot into an amyloid-like form, generating fibrinaloid microclots (2–200 μm) that are highly resistant to fibrinolysis. In this study, archived clots from eight ischemic stroke patients with large vessel occlusion were examined, using samples stored in the Walton Centre Clot Bank in Liverpool, UK. All clots exhibited strong, heterogeneous amyloid staining, revealing a pervasive amyloid component. These findings represent a previously unreported characteristic of stroke clots, highlighting the potential for amyloid-targeted therapies to overcome their fibrinolytic resistance and providing a foundational new insight into ischaemic stroke pathophysiology and treatment.
AI-enabled conversational agent increases engagement with cognitive-behavioral therapy: A randomized controlled trial
Authors: McFadyen Jessica , Habicht Johanna , Dina Larisa-Maria , Harper Ross , Hauser Tobias U. , Rollwage Max 
Published: November 2024

AbstractTimely support after referral to mental healthcare is crucial, yet patients often face prolonged wait times without intervention. Digital mental health interventions offer scalable solutions, but many struggle to achieve acceptable patient engagement. Tailoring and personalizing materials to individual needs is paramount for driving engagement, a task that generative artificial intelligence AI (genAI) is potentially able to achieve. To examine this promise, we conducted a randomized controlled trial using a genAI-enabled therapy app, Limbic Care, which delivers personalized cognitive behavioral therapy (CBT) materials, against PDF workbooks delivering static CBT content, as commonly used in standard care. Adults with elevated symptoms of anxiety or depression (N = 540) were randomly assigned to the app or control group for six weeks. The app group exhibited a threefold increase in engagement (2.4 times higher usage frequency, 3.8 times longer usage durations). While both groups showed similar overall symptom improvement, participants who engaged with the app’s clinical personalization capabilities experienced significantly greater reductions in anxiety symptoms and enhanced well-being than those who engaged with the standard CBT materials. Importantly, the app was safe, with no increase in adverse events compared to standard care. Our findings suggest that genAI-enabled therapy apps can safely enhance patient engagement and improve clinical outcomes through clinically personalized interventions.