bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolutionary Dynamics of Lineage-Specific Class-A GPCR Subsets Reveal Widespread Chemosensory Roles and Adaptations in Lophotrochozoa
Authors: Nath Rohan , Panda Biswajit , Siuli Rakesh , Krishnan Arunkumar
Published: July 2024

Detecting external chemosensory cues via Class-A G protein-coupled receptors (GPCRs) is essential for behavioral and biological functions, influencing animal evolution and ecological adaptations. While well-studied in vertebrates and echinoderms, their role in major clades like Lophotrochozoa is less understood despite their remarkable ecological adaptations. Utilizing 238 lophotrochozoan genomes across eight phyla, we conducted a large-scale comparative genomics analysis to identify lineage-specifically expanded subsets (LSEs) of Class-A GPCRs adapted for chemoreception. Using phylogeny and orthology-based clustering, we differentiated these expansions from conserved orthogroups of endogenous ligand-binding GPCRs. LSEs correlated with adaptations to diverse habitats, with whole-genome duplications having limited impact. Across phyla, species in coastal, freshwater, and terrestrial habitats exhibited large and diverse LSEs, while those adapted to extreme deep-sea environments, parasitic lifestyles, or alternative chemosensory mechanisms showed consistent reductions. Sequence heterogeneity, positive selection, and ligand-binding pocket flexibility in these LSEs further underscored adaptations to environmental signals. These findings provide foundational insights into Class-A GPCR-mediated chemoreception across Lophotrochozoa.

Teaser

Unveiling correlations between lophotrochozoans habitat adaptations and lineage-specific changes in Class-A GPCR repertoire.
The barley MLA13-AVRA13heterodimer reveals principles for immunoreceptor recognition of RNase-like powdery mildew effectors
Authors: Lawson Aaron W. , Flores-Ibarra Andrea , Cao Yu , An Chunpeng , Neumann Ulla , Gunkel Monika , Saur Isabel M. L. , Chai Jijie , Behrmann Elmar , Schulze-Lefert Paul
Published: July 2024

Co-evolution between cereals and pathogenic grass powdery mildew fungi is exemplified by sequence diversification of an allelic series of barley resistance genes encoding Mildew Locus A (MLA) nucleotide-binding leucine-rich repeat (NLR) immunoreceptors with a N-terminal coiled-coil domain (CNLs). Each immunoreceptor recognises a matching, strain-specific powdery mildew effector encoded by an avirulence gene (AVRa). We present here the cryo-EM structure of barley MLA13 in complex with its cognate effector AVRA13-1. The effector adopts an RNase-like fold when bound to MLA13in planta, similar to crystal structures of other RNase-like AVRA effectors purified fromE. coli. AVRA13-1 interactsviaits basal loops with MLA13 C-terminal leucine rich repeats (LRRs) and the central winged helix domain (WHD). Co-expression of structure-guided MLA13 and AVRA13-1 substitution variants show that the receptor–effector interface plays an essential role in mediating immunity-associated plant cell death. Furthermore, by combining structural information from the MLA13–AVRA13-1 heterocomplex with sequence alignments of other MLA receptors, we designed a single amino acid substitution in MLA7 that enables expanded effector detection of AVRA13-1 and the virulent variant AVRA13-V2. In contrast to the pentameric conformation of previously reported effector-activated CNL resistosomes, MLA13 was purified and resolved as a stable heterodimer from anin plantaexpression system. Our study suggests that the MLA13–AVRA13-1 heterodimer might represent a CNL output distinct from CNL resistosomes and highlights opportunities for the development of designer gain-of-function NLRs.
Spatial patterns of vascular plant species richness in Poland: relations among species group richness and hot spot locations
Authors: Szymura T.H. , Tegegne H. , Szymura M.
Published: July 2024

Knowledge of spatial patterns of species richness (SR) is highly relevant for theoretical research in ecology and the development of conservation plans. In Poland, despite a long tradition of botanical surveys, vascular plant SR has not been mapped, nor have the correlations in richness among different plant species groups been explored. Here we used a recently published data set to examine spatial patterns and relationships among the joined SR of vascular plant species, including native species, archeophytes, neophytes, and species with high conservation value (i.e., red list species). The basic spatial unit employed was a 10 × 10 km grid from the Atlas of Distribution of Vascular Plants in Poland (ATPOL). We found that the richness patterns of native species, archeophytes, neophytes, and red-list species were positively correlated. The main patterns of SR and the percentage of particular groups in the joined SR were based on three components: (1) gradient of overall SR, (2) invasion level, and (3) peculiarity of flora in some regions resulting from the high number and proportion of rare species that often have high conservation value. In general, northeastern Poland was species-poor, while the Carpathian Mountain range, the uplands in southern Poland, and some parts of Wisła River valley had the highest SR concentrations. The location of SR hotspots usually did not overlap with the existing system of national parks. The correlations among native SR, high conservation value species, and neophyte SR suggest that biological invasions are among the most important threats to vascular plant diversity in Poland. Finally, we demonstrated that the presented maps, despite likely biases in SR assessments, seem to reflect general ecological gradients influencing vascular plant distribution in Poland.
Towards a Taxonomy Machine – A Training Set of 5.6 Million Arthropod Images
Authors: Steinke D , Ratnasingham S , Agda J , Ait Boutou H , Box I , Boyle M , Chan D , Feng C , Lowe SC , McKeown JTA , McLeod J , Sanchez A , Smith I , Walker S , Wei CY-Y , Hebert PDN
Published: July 2024

The taxonomic identification of organisms from images is an active research area within the machine learning community. Current algorithms are very effective for object recognition and discrimination, but they require extensive training datasets to generate reliable assignments. This study releases 5.6 million images with representatives from 10 arthropod classes and 26 insect orders. All images were taken using a Keyence VHX-7000 Digital Microscope system with an automatic stage to permit high-resolution (4K) microphotography. Providing phenotypic data for 324,000 species derived from 48 countries, this release represents, by far, the largest dataset of standardized arthropod images. As such, this dataset is well suited for testing the efficacy of machine learning algorithms for identifying specimens to higher taxonomic categories.
Convolvulaceae of Guinea: taxonomy, conservation and useful plants
Authors: Davis Becca , Couch Charlotte , Bidault Ehoarn , Simbiano Faya Julien , Moumou Denise , Felipe Almeida Rafael , Simões Ana Rita G.
Published: July 2024

Convolvulaceae is a diverse and economically important plant family in Tropical Africa, including the crop sweet potato (Ipomoea batatas(L.) Lam.) and its wild relatives, morning glories (IpomoeaL.), bindweeds (ConvolvulusL.), invasive weeds (e.g.CuscutaL.) and several other species with food, medicinal, or traditional uses. A taxonomic treatment of Convolvulaceae for Guinea is here presented, including comprehensive morphological descriptions, identification keys to genera and species, distribution and ecological information, specimen data, and documentation of known uses. A total of 51 species belonging to 16 genera are documented, 38 of which are native, and 13 presumed introduced; 33 of these are used as medicine, 18 as ornamental, 12 as food and 15 with a range of other uses. Preliminary IUCN Red List assessments were carried out for 45 species for which there were no previous assessments All 45 preliminary conservation assessments were categorised as Least Concern for the global Red List, with 61% of native species having at least one occurrence point falling within protected areas.
Comparison of black soldier fly, cricket, and superworm on growth performance, nutrient utilization and fatty acid profiles of rainbow trout
Authors: Drosdowech Sonja , Chiasson Marcia , Ma David , Huyben David , Rooney Neil
Published: July 2024

Inclusion of fishmeal and fish oil in feeds for farmed fish is not sustainable and alternatives need to be evaluated. The aim of this study was to determine the effect of diets including defatted black soldier fly larvae (Hermetia illucens), adult cricket (Gryllodes sigillatus) and superworm (Zophobas morio) on the growth performance, apparent nutrient digestibility, nutrient retention, and fatty acid profiles of juvenile rainbow trout (Oncorhynchus mykiss). Triplicate tanks of fish (100.5 ± 0.6 g; mean ± SD) were fed one of four diets, a control diet with 20% fishmeal, and three experimental diets containing either 15% defatted black soldier fly meal, 15% full-fat adult cricket meal or 15% full-fat superworm meal, where each insect meal partially replaced fishmeal and fish oil. After 84 days of feeding, no significant differences were observed between diets for growth performance indicators or body indices. Fish fed the control and superworm diets had a higher protein content and retention in whole-body carcass compared to the cricket and black soldier fly diet groups. No significant effects between diets were found on whole-body carcass regarding fatty acid classes SFA, MUFA, PUFA n-3 and PUFA n-6, although lauric acid and myristic acid were significantly higher in fish fed black soldier fly diet and linoleic acid was higher in fish fed superworm and cricket diets. Retention of fatty acids was higher for most classes in fish fed the black soldier fly diet, yet whole carcass lipid content did not differ significantly between diets. Additionally, apparent digestibility of phosphorous was significantly improved for all insect diets compared to the control. These results indicate that insect meals can partially replace fishmeal and fish oil in diets for rainbow trout without compromising growth performance and fatty acid composition, while improving phosphorous utilization.
Mixtures of Intrinsically Disordered Neuronal Protein Tau and Anionic Liposomes Reveal Distinct Anionic Liposome-Tau Complexes Coexisting with Tau Liquid-Liquid Phase Separated Coacervates
Authors: Tchounwou Christine , Jobanputra Anjali J. , Lasher Dylan , Fletcher Bretton J. , Jacinto Jorge , Bhaduri Arjun , Best Rebecca L. , Fisher William S. , Ewert Kai K. , Li Youli , Feinstein Stuart C. , Safinya Cyrus R.
Published: July 2024

Tau, an intrinsically disordered neuronal protein and polyampholyte with an overall positive charge, is a microtubule (MT) associated protein, which binds to anionic domains of MTs and suppresses their dynamic instability. Aberrant tau-MT interactions are implicated in Alzheimer’s and other neurodegenerative diseases. Here, we studied the interactions between full length human protein tau and other negatively charged binding substrates, as revealed by differential-interference-contrast (DIC) and fluorescence microscopy. As a binding substrate, we chose anionic liposomes (ALs) containing either 1,2-dioleoyl-sn-glycero-3-phosphatidylserine (DOPS, −1e) or 1,2-dioleoyl-sn-glycero-3-phosphatidylglycerol (DOPG, −1e) mixed with zwitterionic 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) to mimic anionic plasma membranes of axons where tau resides. At low salt concentrations (0 to 10 mM KCl or NaCl) with minimal charge screening, reaction mixtures of tau and ALs resulted in the formation of distinct states of AL-tau complexes coexisting with liquid-liquid phase separated tau self-coacervates arising from the polyampholytic nature of tau containing cationic and anionic domains. AL-tau complexes exhibited distinct types of morphologies. This included, large ≈20-30 micron tau-decorated giant vesicles with additional smaller liposomes with bound tau attached to the giant vesicles, and tau-mediated finite-size assemblies of small liposomes. As the ionic strength of the solution was increased to near and above physiological salt concentrations for 1:1 electrolytes (≈150 mM), AL-tau complexes remained stable while tau self-coacervate droplets were found to dissolve indicative of breaking of (anionic/cationic) electrostatic bonds between tau chains due to increased charge screening. The findings are consistent with the hypothesis that distinct cationic domains of tau may interact with anionic lipid domains of the lumen facing monolayer of the axon plasma membrane suggesting the possibility of transient yet robust interactions at physiologically relevant ionic strengths.
CD24a knockout transforms the tumor microenvironment from cold to hot by promoting tumor-killing immune cell infiltration in a murine triple-negative breast cancer model
Authors: Chan Shih-Hsuan , Tseng Hsuan-Jung , Wang Lu-Hai
Published: July 2024

Background

CD24 plays a crucial role not only in promoting tumor progression and metastasis but also in modulating macrophage-mediated anti-tumor immunity. However, the impact of tumor CD24 on the immune landscape of the tumor microenvironment (TME) remains poorly explored. Here, we investigated the role of CD24a, murine CD24 gene, in the progression and immune dynamics of the tumor microenvironment (TME) in the 4T1 murine model of triple-negative breast cancer (TNBC).Methods:We employed Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 technology to perform a gene knockout of Cd24a in 4T1 cells. Flow cytometry was utilized to analyze the distribution and number of immune cells, including myeloid-derived suppressor cells (MDSCs), natural killer (NK) cells, T cells, and macrophages, within tumors, spleens, and bone marrow. Immunofluorescence (IF) staining was used to detect these immune cells in tumor sections. Additionally, ANDOR Dragonfly High-Speed Confocal was used to perform three-dimensional (3D) mapping of mouse tumors.

Results

Our study showed that knocking out CD24a significantly impeded tumor progression and prolonged mouse survival. Flow cytometry and IF analysis revealed that the loss of CD24a transformed tumor microenvironment from cold to hot by promoting the infiltration of M1 macrophages, cytotoxic CD8+T cells, and CD49b+natural killer (NK) cells while reducing the recruitment and expansion of granulocytic myeloid-derived suppressor cells (gMDSCs) in the TME. Additionally, the 3D mapping of TME further validated the “hot state” of CD24a knockout tumors.

Conclusions

Our study provides the first evidence that targeting CD24a could effectively reprogram the TME, enhancing its immunogenicity, and transforming immune cold tumors into hot tumors. This strategy may offer a promising therapeutic strategy for enhancing the immune response against poorly immunogenic tumors.
HIV-1-envelope trimer transitions from prefusion-closed to CD4-bound-open conformations through an occluded-intermediate state
Authors: Lee Myungjin , Lu Maolin , Zhang Baoshan , Zhou Tongqing , Katte Revansiddha , Han Yang , Rawi Reda , Kwong Peter D.
Published: July 2024

HIV-1 infection is initiated by the interaction between the gp120 subunit in the envelope (Env) trimer and the cellular receptor CD4 on host cells. This interaction induces substantial structural rearrangement of the Env trimer. Currently, static structural information for prefusion-closed trimers, CD4-bound prefusion-open trimers, and various antibody-bound trimers is available. However, dynamic features between these static states (e.g., transition structures) are not well understood. Here, we investigate the full transition pathway of a site specifically glycosylated Env trimer between prefusion-closed and CD4-bound-open conformations by collective molecular dynamics and single-molecule Förster resonance energy transfer (smFRET). Our investigations reveal and confirm important features of the transition pathway, including movement of variable loops to generate a glycan hole at the trimer apex and formation or rearrangements of α-helices and β-strands. Notably, by comparing the transition pathway to known Env-structures, we uncover evidence for a transition intermediate, with four antibodies, Ab1303, Ab1573, b12, and DH851.3, recognizing this intermediate. Each of these four antibodies induce population shifts of Env to occupy a newly observed smFRET state: the “occluded-intermediate” state. We propose this occluded-intermediate state to be both a prevalent state of Env and an on-path conformation between prefusion-closed and CD4-bound-open states, previously overlooked in smFRET analyses.
A focal traumatic injury to the spinal cord causes an immediate and massive spreading depolarization sustained by chloride ions, with transient network dysfunction and remote cortical glia changes
Authors: Mohammadshirazi Atiyeh , Mazzone Graciela L. , Zylberberg Benjamín A. , Mio Luca , Pistorio Giulio , Falcone Carmen , Taccola Giuliano
Published: July 2024

In clinics, physical injuries to the spinal cord cause a temporary motor areflexia below lesion, known as spinal shock. This topic is still underexplored due to the lack of preclinical SCI models that do not use anesthesia, which would affect spinal excitability. Our innovative design considered a custom-made micro impactor that provides localized and calibrated strikes to the ventral surface of the thoracic spinal cord of the entire CNS isolated from neonatal rats. Before and after injury, multiple ventral root (VR) recordings continuously traced respiratory rhythm, baseline spontaneous activities, and electrically-induced reflex responses. As early as 200 ms after impact, an immediate transient depolarization spread from the injury site to the whole spinal cord with distinct segmental velocities. Stronger strikes induced higher potentials causing, at the site of injury, a transient drop in tissue oxygen levels and a massive cell death with complete disconnection of longitudinal tracts. Below the impact site, expiratory rhythm and spontaneous lumbar activity were suppressed. On lumbar VRs, reflex responses transiently halted but later recovered to control values, while electrically-induced fictive locomotion remained perturbed. Moreover, low-ion modified Krebs solutions differently influenced impact-induced depolarizations, the magnitude of which amplified in low-Cl−. Moreover, remote changes in cortical glia occurred soon after spinal damage. Overall, our novel in vitro platform traces the immediate functional consequences of impacts to the spinal cord during development. This basic study provides insights on the SCI pathophysiology, unveiling an immediate chloride dysregulation and transient remote glial changes in the cortex.
Subcellular ToF-SIMS imaging of the snow algaSanguina nivaloidesby combining high mass and high lateral resolution acquisitions
Authors: Seydoux Claire , Ezzedine Jade A. , Larbi Grégory Si , Ravanel Stéphane , Maréchal Eric , Barnes Jean-Paul , Jouneau Pierre-Henri
Published: July 2024

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging has demonstrated great potential for metabolic imaging, yet achieving sufficiently high lateral and mass resolution to reach the organelle scale remains challenging. We have developed an approach by combining ToF-SIMS imaging acquisitions at high lateral resolution (> 150 nm) and high mass resolution (9,000). The data were then merged and processed using multivariate analysis (MVA), allowing for the precise identification and annotation of 85% of the main contributors to the multivariate analysis components at high lateral resolution. Insights into the electron microscopy sample preparation are provided, especially as we reveal that at least three different osmium-containing complexes can be found depending on the specific chemical environment of organelles. In cells of the snow algaSanguina nivaloides, living in a natural environment limited in nutrients such as phosphorus (P), we were able to map elements and molecules within their subcellular context, allowing for the molecular fingerprinting of organelles at a resolution of 100 nm, as confirmed by correlative electron microscopy. It was thus possible to highlight thatS. nivaloideslikely absorbed selectively some inorganic P forms provided by P-rich dust deposited on the snow surface.S. nivaloidescells could maintain phosphorylations in the stroma of the chloroplast, consistently with the preservation of photosynthetic activity. The presented method can thus overcome the current limitations of ToF-SIMS for subcellular imaging and contribute to the understanding of key questions such as P homeostasis and other cell physiological processes.
NanoLAS 2.0: A Comprehensive Update on a Nanobody-Focused Platform with Advanced Visualization and Docking Simulation Features
Authors: Zheng Zebiao , Qin Wei , Yu Kangrui , Hong Yangqi , Tang Yongqi , Wang Tiantai , Liang Lixin , Huang Bingding , Wang Xin
Published: July 2024

Nanobodies, a unique subclass of antibodies initially discovered in camelids, characterized by the absence of light chains and consisting solely of a heavy chain variable region. This distinctive structure endows nanobodies with inherent advantages in the realms of disease treatment and biopharmaceutical applications. Presently, research and applications concerning nanobodies are experiencing rapid growth. However, existing databases suffer from non-uniform data sources and a lack of data standardization. To address these issues, we developed the NanoLAS database in 2023. Despite the progress in data integration made by NanoLAS, there was room for improvement in search functionality, three-dimensional structural display, and other areas. Building upon this foundation, we introduce the comprehensively updated NanoLAS 2.0. This version offers updates to data sources, precise 3D structural presentation, and molecular docking simulation capabilities, refines the multi-condition search mechanism, and incorporates a brand-new sequence viewer as well as epitope prediction functionality. Additionally, to cater to the needs of researchers, we have designed a user-friendly and intuitive interface. In summary, we anticipate that NanoLAS 2.0 will serve as a powerful and easy-to-use research tool, facilitating researchers in their exploration of nanobodies and propelling advancements in the field of nanobody research and application.

Availability

NanoLAS 2.0 is available athttps://www.nanolas2.online

Contact

bingdinghuang@sztu.edu.cnandwangxin@sztu.edu.cn
Optimal sigmoid function models for analysis of transspinal evoked potential recruitment curves recorded from different muscles
Authors: Skiadopoulos Andreas , Knikou Maria
Published: July 2024

Recruitment input-output curves of transspinal evoked potentials that represent the net spinal motor output of alpha motor neurons, and those of cortically, spinally or peripherally induced responses are used extensively in research as neurophysiological biomarkers to establish physiological or pathological behavior of neuronal networks as well as post-treatment recovery. A comparison between different sigmoidal models to fit the transspinal evoked potentials recruitment curve and estimate the parameters of physiological importance has not been performed. This study sought to address this gap by fitting eight sigmoidal models (Boltzmann, Hill, Log-Logistic, Log-Normal, Weibull-1, Weibull-2, Gompertz, Extreme Value Function) to the transspinal evoked potentials recruitment curves of soleus and tibialis anterior recorded under four different cathodal stimulation settings. The sigmoidal models were ranked based on the Akaike information criterion, and their performance was assessed in terms of Akaike differences and weights values. Additionally, an interclass correlation coefficient between the predicted parameters derived from the best models fitted to the recruitment curves was also established. A Bland-Altman analysis was conducted to evaluate the agreement between the predicted parameters from the best models. The findings revealed a muscle dependency, with the Boltzmann and Hill models identified as the best fits for the soleus, while the Extreme Value Function and Boltzmann models were optimal for the tibialis anterior transspinal evoked potentials recruitment curves. Excellent agreement for the upper asymptote, slope, and inflection point parameters was found between Boltzmann and Hill models for the soleus, and for slope and inflection point parameters between Extreme Value Function and Boltzmann models for the tibialis anterior. Notably, the Boltzmann model for soleus and the Extreme Value Function model for tibialis anterior exhibited less susceptibility to inaccuracies in estimated parameters. Based on these findings, we suggest the Boltzmann and the Extreme Value Function models for fitting the soleus and the tibialis anterior transspinal evoked potentials recruitment curve, respectively.
A novel repressor-activator-competitor module comprising C2H2zinc finger and NAC transcription factors regulates rice grain development
Authors: Jaiswal Priya , Priyadarshini Richa , Yadav Antima , Aswathi P V , Mahto Arunima , Mathew Iny Elizebeth , Das Upasana , Qasim Falah , Vichitra Ankur , Panwar Akanksha , Verma Ankit , Tyagi Akhilesh K. , Agarwal Pinky
Published: July 2024

Grain size and quality are crucial agronomic traits. We have characterized a seed-preferential C2H2zinc finger transcriptional repressor,ZOS1-15. Its overexpression, knock-down and knock-out plants indicated a negative control over grain size due to altered cell expansion. ZOS1-15 homodimerized and directly interacted with co-repressor TOPLESS and histone deacetylases to form a repression complex. ZOS1-15 also interacted with Mediator subunit MED14_1 and a seed-preferential transcriptional activator, ONAC024, with three alternatively spliced isoforms. The ectopic expression ofONAC024negatively affected plant growth and development. Seed-preferential overexpression and knock-down plants showed ONAC024 as a positive regulator of grain length due to increased cell proliferation and expansion. CRES-T generated transgenic rice plants indicated a functional divergence amongst ONAC024 isoforms. Tandem interactions were observed between ONAC024-ONAC023-ONAC026-ONAC020. ZOS1-15 and ONAC024 functioned antagonistically to regulate grain amylose and SSP accumulation while ONAC023 affected only amylose. ZOS1-15 and ONAC024 directly regulated the expression of two SSP encoding genes. Binding of ONAC024 was competed by ONAC025-MADS29 complex. The seed-preferential overexpression of SS1/ ONAC025 resulted in decreased grain size and amylose content, but higher yield. This study proposes a ’repressor-activator-competitor’ module, wherein ZOS1-15, ONAC024, ONAC023, ONAC025 along with their interactors synergistically and antagonistically regulate multiple aspects of rice grain development.
Vesicle Picker: A tool for efficient identification of membrane protein complexes in vesicles
Authors: Karimi Ryan , Coupland Claire E. , Rubinstein John L.
Published: July 2024

Electron cryomicroscopy (cryo-EM) has recently allowed determination of near-atomic resolution structures of membrane proteins and protein complexes embedded in lipid vesicles. However, particle selection from electron micrographs of these vesicles can be challenging due to the strong signal contributed from the lipid bilayer. This challenge often requires iterative and laborious particle selection workflows to generate a dataset of high-quality particle images for subsequent analysis. Here we present Vesicle Picker, an open-source program built on the Segment Anything model. Vesicle Picker enables automatic identification of vesicles in cryo-EM micrographs with high recall and precision. It then exhaustively selects all potential particle locations, either at the perimeter or uniformly over the surface of the projection of the vesicle. The program is designed to interface with cryoSPARC, which performs both upstream micrograph processing and downstream single particle image analysis. We demonstrate Vesicle Picker’s utility by determining a high-resolution map of the vacuolar-type ATPase from micrographs of native synaptic vesicles (SVs) and identifying an additional protein or protein complex in the SV membrane.
Systematically investigating and identifying bacteriocins in the human gut microbiome
Authors: Zhang Dengwei , Zou Yinai , Shi Yuqi , Zhang Junliang , Liu Jing , Wu Gengfan , Zhang Jian , Gao Ying , Chen Muxuan , Li Yong-Xin
Published: July 2024

Human gut microbiota produces unmodified bacteriocins, natural antimicrobial peptides that protect against pathogens and regulate host physiology. However, current bioinformatic tools limit the comprehensive investigation of bacteriocins’ biosynthesis, obstructing research into their biological functions. Here, we introduce IIBacFinder, a superior analysis pipeline for identifying unmodified class II bacteriocins. Through large-scale bioinformatic analysis and experimental validation, we demonstrate their widespread distribution across the bacterial kingdom, with being niche-specific and enriched in the human microbiome. Analyzing over 280,000 bacterial genomes, we reveal the diverse potential of human gut bacteria to produce these bacteriocins. Guided by meta-omics analysis, we synthesized 26 hypothetical bacteriocins from gut commensal species, with 16 showing antibacterial activities. Furtherex vivotests show minimal impact of narrow-spectrum bacteriocins on human fecal microbiota. Our study highlights the huge biosynthetic potential of unmodified bacteriocins in the human gut, paving the way for understanding their biological functions and health implications.
Adaptive Dynamic Social Networks Using an Agent-Based Model to Study the Role of Social Awareness in Infectious Disease Spread
Authors: López Leonardo , Giovanini Leonardo
Published: July 2024

The synergy between the spread of infectious diseases and individual behavior is widely recognized. Our pioneering methodology introduces a model based on agents embedded within adaptive temporal networks, providing a nuanced portrayal of daily interactions through an agent-based paradigm. Each agent encapsulates the interactions of individuals, with external stimuli and environmental cues influencing their conduct. Comprising three intertwined elements—individual behavior, social dynamics, and epidemiological factors—the model has been validated against real-world influenza outbreaks, demonstrating superior performance compared to traditional methodologies. Our framework exhibits extensive versatility and applicability by encapsulating individual-level dynamics through elementary rules and simulating complex social behaviors such as social consciousness.
CARDIO-QVARK Diagnose Ischemic Myocardiocyte!
Authors: Marzoog Basheer Abdullah , Chomakhidze Peter , Suvorov Alexander , Kopylov Philipp
Published: July 2024

Background

Ischemic heart disease (IHD) has the highest mortality rate in the globe. This returns to the poor diagnostic and therapeutic strategies including the early prevention methods.

Aims

To assess the changes in the single channel electrocardiography (SCECG) at rest and on exercise test in patients with vs without IHD confirmed by stress computed tomography myocardial perfusion (CTP) imaging with vasodilatation stress-test.

Objectives

IHD frequently have preventable risk factors and causes that lead to the disease appearance. However, the lack of the proper diagnostic and prevention tools remains a global challenge in or era despite the current scientific advances.

Material and methods

A single center observational study included 80 participants from Moscow. The participants aged ≥ 40 years and given a written consent to participate in the study. Both groups, G1=31 with vs G2=49 without post stress induced myocardial perfusion defect, passed cardiologist consultation, anthropometric measurements, blood pressure and pulse rate, echocardiography, cardio-ankle vascular index, performing bicycle ergometry, recording 3-minutes SCECG (using CARDO-QVARK) before and just after bicycle ergometry, and then performing CTP. The LASSO regression with nested cross-validation was used to find association between CARDO-QVARK parameters and the existence of the perfusion defect. Statistical processing carried out using the R programming language v4.2, Python v.3.10 [^R], and Statistica 12 programme.

Results

The CARDO-QVARK parameters analysis have a specificity 75.5 % [95 % confidence interval (CI); 0.628; 0.88], sensitivity 51.6 % [95 % CI; 0.333; 0.695], area under the curve (AUC) 67 % [95 % CI; 0.530; 0.801] in compare to bicycle ergometry AUC; 50.7 % [95 % CI; 0.388; 0.625], specificity 53.1 % [95 % CI; 0.392; 0.673], sensitivity 48.4 % [95 % CI; 0.306; 0.657], based on our study results.

Conclusion

The SCECG have no statistically significant higher diagnostic accuracy in compare to bicycle ergometry. However, CARDO-QVARK has the potential to improve the diagnostic accuracy of the bicycle ergometry.

Other

Further investigations required to uncover the hidden capabilities of CARDO-QVARK in the diagnosis of ischemic heart disease.
CLINICAL AND COGNITIVE PHENOTYPING OF COPY NUMBER VARIANTS PATHOGENIC FOR NEURODEVELOPMENTAL DISORDERS FROM A MULTI-ANCESTRY BIOBANK
Authors: Zaks Nina , Mahjani Behrang , Reichenberg Abraham , Birnbaum Rebecca
Published: July 2024

Background

Rare copy number variants (CNVs) are pathogenic for neurodevelopmental disorders (NDDs) and effect neurocognitive impairment. In aggregate, NDD CNVs may present in up to 2% of population cohorts with implications for neuropsychiatric disease risk and cognitive health. However, analyses of NDD CNVs in biobanks or population cohorts have been hindered by limited clinical or cognitive phenotypes, and a lack of ancestral diversity. In the current proof-of-concept study, NDD CNV carriers were recontacted from BioMe, a multi-ancestry biobank derived from the Mount Sinai healthcare system, to enable ‘deep phenotyping’ beyond electronic health record outcomes.

Methods

From BioMebiobank, 892 adult participants were recontacted, including 335 harboring NDD CNVs, 217 with schizophrenia and 340 neurotypical controls as comparators. Clinical and cognitive assessments were administered to each recruited participant.

Results

Seventy-three participants completed study assessments (mean age=48.8 years; 66% female; 36% African, 26% European, 34% Hispanic), or 8% of the recontacted subset, including 30 NDD CNV carriers across 15 loci. Among NDD CNV carriers, assessments indicated 40% with mood and anxiety disorders, 30% with learning disorders, and 13% with a history of special education. NDD CNV carriers were significantly cognitively impaired compared to controls on digit span backwards (Beta=-1.76, FDR=0.04) and digit span sequencing (Beta=-2.01, FDR=0.04).

Conclusions

Feasibility of “recall-by-genotype” from a multi-ancestry biobank was established for NDD CNV carriers, along with comparator groups. The current study corroborated past reports of NDD CNVs effects of cognitive impairment, while elucidating clinical phenotypes for recalled individuals. Future “recall-by-genotype” studies may further facilitate clinical characterization of disease-relevant genomic variants.
Apathy, intentions, explicit attitudes, and approach-avoidance tendencies in physical activity behavior
Authors: Farajzadeh Ata , Jabouille François , Benoit Nickolas , Bezeau Olivier , Bourgie Tristan , Gerro Benjamin , Ouimet Jacob , Boisgontier Matthieu P.
Published: July 2024

Background

Greater behavioral apathy has been shown to be associated with lower engagement in physical activity. However, the mechanisms underlying this association remain overlooked and poorly understood. Intentions, explicit attitudes, and approach-avoidance tendencies toward physical activity may play a central role in the relationship, given their strong links to motivation and physical activity.

Methods

An online study was conducted in 365 participants aged 54±18 years. All measures were assessed using questionnaires, except approach-avoidance tendencies, which were derived from reaction times in an approach-avoidance task. Component mediation analyses based on multiple linear regressions were conducted to examine whether the intention to be physically active mediated the relationship between behavioral apathy levels and usual physical activity levels, and whether explicit attitudes and approach-avoidance tendencies mediated the relationship between behavioral apathy and the intention.

Results

Results showed that weaker intentions to be physically active mediated the association between higher behavioral apathy and lower usual weekly levels of moderate-to-vigorous physical activity. In addition, explicit attitudes mediated the effect of behavioral apathy on intentions to be physically active. Results on approach-avoidance tendencies showed a significant three-way interaction between apathy, stimulus (physical activity vs. sedentary behavior), and action direction (approach vs. avoidance) on corrected reaction time (b = 19.6; 95CI = 2.0 to 37.3; p = .029), with higher apathy being associated with a greater tendency to avoid physical activity stimuli and to approach sedentary stimuli. However, we found no evidence suggesting that these tendencies mediated the effect of apathy on intentions or habitual physical activity. Based on our data, a mean item score greater than 34.5% of the scale range (e.g., >3.07 on a 1–7 scale) is indicative of behavioral apathy.

Conclusion

This study provides new insights into the role of intentions, explicit attitudes, and approach-avoidance tendencies toward physical activity in the relationship between behavioral apathy levels and the engagement in physical activity.
Performance of Wearable Pulse Oximetry During Controlled Hypoxia Induction
Authors: Jiang Yihang , Spies Connor , Roghanizad Ali R. , Bhosai Satasuk Joy , Snyder Laurie , Burke Ashley , MacLeod David , Dunn Jessilyn
Published: July 2024

Oxygen saturation is a crucial metric used for monitoring patients with lung disease or other conditions who are at risk of hypoxemia. Recently, consumer wearable devices began incorporating oxygen saturation measurement tools, widening their use among individuals with lung disease. However, their performance has not been well characterized, particularly during blood oxygen desaturation, due to limitations in collecting comparison arterial blood gas measurements during exercise-induced hypoxemia. To address this knowledge gap, we performed a controlled oxygen desaturation study in nine healthy participants to mimic exercise-induced hypoxemia, reducing the blood oxygen saturation levels from 100% to 60% using a gas delivery system. We conducted a comparative analysis of the displayed oxygen saturation readings of both the Masimo MightySat Rx finger pulse oximeter and Apple Watch Series 7 with arterial blood oxygen saturation readings obtained from arterial blood gas samples. Both the Masimo MightySat Rx pulse oximeter and the Apple Watch Series 7 tended to overestimate the oxygen saturation. The Masimo pulse oximeter readings were more likely to fall within the acceptable error range than the Apple Watch (49.03% compared to 32.14%). Notably, both devices have limitations under low oxygen saturation levels (<88%) with an error of 1.96% and 4.99% for the Masimo and Apple Watch, respectively. Among the oxygen desaturation measurements at a desaturation rate larger than two percent per minute, a rate which is clinically correlated to sleep apnea, both devices increased their error slightly by 0.29% and 1.80% respectively for the Masimo and Apple Watch. However, no statistically significant increase was found.

Author Summary

Blood oxygen saturation (SpO2) is an important measurement for monitoring patients with acute and chronic conditions that are associated with hypoxemia, including chronic obstructive pulmonary disease (COPD), heart failure, and sleep apnea. While smartwatches may provide a novel method for continuous and unobtrusive SpO2monitoring, it is necessary to understand their accuracy and limitations to ensure that they are used in a fit-for-purpose manner, especially under conditions of low oxygen saturation.
Lower levels of household transmission of SARS-CoV-2 VOC Omicron compared to Wild-type: an interplay between transmissibility and immune status
Authors: Winkel AMAM , Kozanli E , Haverkort ME , Euser SM , Sluiter-Post JGC , Mariman R , Vogelzang A. , de Bakker J. , Lap C.R. , van Houten MA , Eggink D , van Lelyveld SFL
Published: July 2024

Background

Knowledge of SARS-CoV-2 household transmission dynamics guides infection control and vaccination measures. This household cohort study prospectively assessed the impact of both the Omicron BA.2 variant and immunity on household transmission using dense saliva sampling and sequence analysis.

Methods

Households consisting of a PCR-confirmed index and at least two household members were enrolled in March and April 2022 during the Omicron BA.2 wave in the Netherlands. SARS-CoV-2 PCR was performed on ten consecutive saliva samples. Serum-antibodies were measured at baseline and day 42. Whole genome sequencing was performed for phylogenetic analysis, followed by sensitivity analysis, to correct for multiple household introductions and index definition. Results were compared with the identical, early-pandemic and pre- immunisation predecessor study.

Results

Sixty-seven households were included, consisting of 241 individuals (median age 33.0 years). Maximum household Secondary Attack Rate (SAR) was 59.7%, per-person SAR 41.5%. Underage indexes were more likely to transmit. Transmission was negatively affected by household members’ immunity. Phylogenetic analysis showed multiple introductions in four households. Sensitivity analysis resulted in a minimal household SAR of 51.0% and per-person SAR of 28.5%.

Conclusions

The Omicron BA.2 variant is highly transmissible within households. Nevertheless, transmission rates are lower than our pre-immunisation reported ancestral rates: household SAR decreased from 88.2% to 59.7%, per-person SAR from 64.3% to 41.5%, implying immunity reduces transmission, even for a more transmittable variant. Regardless of immune status, children have a crucial role in Omicron household transmission. Intensive sampling and phylogenetic analysis are essential to correctly calculate transmission rate, especially in times of minimal behavioural restrictions.
PhotoFiTT: A Quantitative Framework for Assessing Phototoxicity in Live-Cell Microscopy Experiments
Authors: Del Rosario Mario , Gómez-de-Mariscal Estibaliz , Morgado Leonor , Portela Raquel , Jacquemet Guillaume , Pereira Pedro M. , Henriques Ricardo
Published: July 2024

Phototoxicity in live-cell fluorescence microscopy can compromise experimental outcomes, yet quantitative methods to assess its impact remain limited. Here we present PhotoFiTT (Phototoxicity Fitness Time Trial), an integrated framework combining a standardised experimental protocol with advanced image analysis to quantify light-induced cellular stress in label-free settings. PhotoFiTT leverages machine learning and cell cycle dynamics to analyse mitotic timing, cell size changes, and overall cellular activity in response to controlled light exposure. Using adherent mammalian cells, we demonstrate PhotoFiTT’s ability to detect wavelength- and dose-dependent effects, showcasing that near-UV light induces significant mitotic delays at doses as low as 0.6J/cm2, while longer wavelengths require higher doses for comparable effects. PhotoFiTT enables researchers to establish quantitative benchmarks for acceptable levels of photodamage, facilitating the optimisation of imaging protocols that balance image quality with sample health.
A multiscale model of the action of a capsid assembly modulator for the treatment of chronic hepatitis B
Authors: Iyaniwura Sarafa A. , Cassidy Tyler , Ribeiro Ruy M. , Perelson Alan S.
Published: July 2024

Chronic hepatitis B virus (HBV) infection is strongly associated with increased risk of liver cancer and cirrhosis. While existing treatments effectively inhibit the HBV life cycle, viral rebound occurs rapidly following treatment interruption. Consequently, functional cure rates of chronic HBV infection remain low and there is increased interest in a novel treatment modality, capsid assembly modulators (CAMs). Here, we develop a multiscale mathematical model of CAM treatment in chronic HBV infection. By fitting the model to participant data from a phase I trial of the first-generation CAM vebicorvir, we estimate the drug’s dose-dependent effectiveness and identify the physiological mechanisms that drive the observed biphasic decline in HBV DNA and RNA, and mechanistic differences between HBeAg-positive and negative infection. Finally, we demonstrate analytically and numerically that HBV RNA is more sensitive than HBV DNA to increases in CAM effectiveness.

Author summary

Capsid assembly modulators (CAMs) are a novel class of anti-hepatitis B virus (HBV) treatments in clinical trials. These CAMs have a distinct mechanism of action from nucleos(t)ide analogues and thus represent an attractive option for the treatment of chronic HBV infection. We developed a multiscale model of the intracellular HBV lifecycle and extracellular dynamics using a time-since-infection structured partial differential equation. We fit the model to participant data from a recent phase I trial, performed a detailed parameter sensitivity analysis, identified key mechanisms driving viral response to first-generation CAM treatment, and demonstrated that HBV RNA is more sensitive than HBV DNA to changes in CAM efficacy, highlighting the potential role of HBV RNA as a biomarker for CAM effectiveness.