bluuebunny/crossref_metadata_2025 huggingface dataset:
Generating realistic neurophysiological time series with denoising diffusion probabilistic models
Authors: Vetter Julius , Macke Jakob H. , Gao Richard
Published: August 2023

In recent years, deep generative models have had a profound impact in engineering and sciences, revolutionizing domains such as image and audio generation, as well as advancing our ability to model scientific data. In particular, Denoising Diffusion Probabilistic Models (DDPMs) have been shown to accurately model time series as complex high-dimensional probability distributions. Experimental and clinical neuroscience also stand to benefit from this progress, since accurate modeling of neurophysiological time series, such as electroencephalography (EEG), electrocorticography (ECoG), and local field potential (LFP) recordings, and their synthetic generation can enable or improve a variety of neuroscientific applications. Here, we present a method for modeling multi-channel and densely sampled neurophysiological recordings using DDPMs, which can be flexibly applied to different recording modalities and experimental configurations. First, we show that DDPMs can generate realistic synthetic data for a variety of datasets including different recording techniques (LFP, ECoG, EEG) and species (rat, macaque, human). DDPM-generated time series accurately capture single- and multi-channel statistics such as frequency spectra and phase-amplitude coupling, as well as fine-grained and dataset-specific features such as sharp wave-ripples. In addition, synthetic time series can be generated based on additional information like experimental conditions or brain states. We demonstrate the utility and flexibility of DDPMs in several neuroscience-specific analyses, such as brain-state classification and imputation of missing channels to improve neural decoding. In summary, DDPMs can serve as accurate generative models of neurophysiological recordings, and have a broad utility in the probabilistic generation of synthetic time series for neuroscientific applications.
Hormonal induction, quality assessments and the influence of seasonality on male reproductive viability in a long-term managedex situbreeding colony of Southern Rocky Mountain Boreal toads,Anaxyrus boreas boreas
Authors: Calatayud N.E. , Jacobs Leah , Togna Gina Della , Langhorne Cecilia J. , Mullen Amanda C. , Upton Rose
Published: August 2023

The Southern Rocky Mountain Boreal Toad (Anaxyrus boreas boreas)is anex situmanaged species which relies heavily on the use of assisted reproductive technologies to augment existingin situpopulations. Despite the use of ARTs to manipulate reproduction of this species, theex situprogram continues to face challenges with annual reproduction. Human chorionic gonadotropin (hCG) at 10 IU/gbw singly or in combination with 0.4 ug/gbw GnRH-A have been successfully reported for this species, however, with a number of other available hormones, it is not clear if these are the most effective protocols for this species. Moreover, there is no information on how exogenous hormone administration is affected by other factors such as seasonality. Therefore, in the first part of this study, we compare the efficacy of the 10 IU/g hCG and 0.4 Lg/g Gonadotropin Releasing Hormone agonist (GnRH-A) administered singly or in combination, as well as GnRH-Apd + Amphiplex (0.4 Lg/g GnRH-A + 10 Lg/g Metoclopramide [MET] - a dopamine antagonist), or 10 Lg/g MET alone. Spermiation responses and sperm viability were compared across treatments with hormonal curves then correlated to seasonality. The results of this study suggest that the optimal hormonal stimulation protocol, across all treatments, in terms of sperm quality was 10 IU/g hCG + 0.4 Lg/g GnRH-A. Further optimization is required, in particular the exploration of higher doses of GnRH-A. Lastly, we observed that the effect of seasonality influenced the hormonal efficacy and magnitude of the spermiation response. As was expected, quality and concentration parameters were affected by the month in which hormone administration occurred.

HIGHLIGHTS

Spermiation in the Southern Rocky Mountain Boreal toad,Anaxyrus boreas boreas,is elicited most effectively by hCG singly or in combination with GnRH-A.

Spermiation responses lasted up to 96 hours post injection (hpi) though quantity and quality parameters were highest in the first 12 hpi.

Total motility, forward progressive motility and percentage live cells all indicatedA. b. boreassperm quality was in a good range.

Acrosome integrity requires more research as it was comparatively lower than expected.

Responses to hormone inductions are seasonally affected in this species but suggest semi-discontinuous cycling.

Ex situ breeding should perform better sperm assessments before designing breeding strategies.
Reconstruction of compartmentalized genome-scale metabolic models using deep learning for over 800 fungi
Authors: Castillo Sandra , Peddinti Gopal , Blomberg Peter , Jouhten Paula
Published: August 2023

Eukaryotic metabolism is organized into subcellular compartments enclosed by lipid-membranes. Since most metabolites do not move freely across the membranes, the compartmentalization influences metabolic pathway connectivities. Thus, compartmentalizing the pathways also in genome-scale metabolic models (GEMs) is essential for accurate predictions of eukaryotic cells’ metabolic phenotypes. Compartmentalization has manually been introduced into the model Eukaryote GEMs like for yeastSaccharomyces cerevisiae. Non-model organisms’ GEMs can be automatically reconstructed from genome data. However, the existing GEM reconstruction methods do not introduce compartmentalization into the models. To that end, we integrated our novel deep learning protein localization prediction and protein functional annotation into a top-down GEM reconstruction for automatically creating species-specific compartmentalized GEMs. We developed also a universal fungal GEM for top-down reconstruction of species-specifically compartmentalized GEMs and reconstructed models for 834 species. The novel protein localization prediction outperformed the state of the art in classifying proteins into multiple compartments and integrating the enzyme localization predictions to functional annotations improved the top-down model reconstruction. Interestingly, the clustering of the fungal GEMs reconstructed with predicted species-specific enzyme localization resembled more closely the phylogenetic relationships of the species than that of the GEMS without the compartmentalization. Compartmentalization of metabolism in fungi differs from other eukaryotes but the enzyme subcellular localizations vary also among fungal species. The Fungal kingdom encompasses species important for human health, environment, and industrial biotechnology. The reconstructed fungal GEM set offers valuable tools for e.g., predicting metabolic phenotypes of e.g., mushrooms or single-cellular fungi, the roles of eukaryotes in microbial communities, designs optimizing eukaryotic hosts for industrial chemical production, and identifying drug targets against pathogenic fungi. Beyond fungi, the compartmentalized GEM reconstruction method allows combining other universal GEMs for developing cell type specific GEMs for higher eukaryotes including plants, insects, and mammals.
Polybacterial intracellular coinfection of epithelial stem cells in periodontitis
Authors: Easter Quinn T. , Matuck Bruno Fernandes , Stark Germán Beldorati , Worth Catherine L. , Predeus Alexander V. , Fremin Brayon , Huynh Khoa , Ranganathan Vaishnavi , Pereira Diana , Weaver Theresa , Miller Kathryn , Perez Paola , Hasuike Akira , Chen Zhaoxu , Bush Mandy , Warner Blake M. , Lee Janice , Wallet Shannon M. , Sequeira Inês , Tyc Katarzyna M. , Liu Jinze , Ko Kang I. , Teichmann Sarah A. , Byrd Kevin M.
Published: August 2023

Periodontitis affects billions of people worldwide. To address interkingdom relationships of microbes and niche on periodontitis, we generated the first sin-gle-cell meta-atlas of human periodontium (34-sample, 105918-cell), harmo-nizing 32 annotations across 4 studies1–4. Highly multiplexed immunofluores-cence (32-antibody; 113910-cell) revealed spatial innate and adaptive immune foci segregation around tooth-adjacent epithelial cells. Sulcular and junctional keratinocytes (SK/JKs) within epithelia skewed toward proinflammatory phe-notypes; diseased JK stem/progenitors displayed altered differentiation states and chemotactic cytokines for innate immune cells. Single-cell metagenomics utilizing unmapped reads revealed 37 bacterial species.16Sand rRNA probes detected polybacterial intracellular pathogenesis (“co-infection”) of 4 species within single cells for the first time in vivo. Challenging coinfected primary human SK/JKs with lipopolysaccharide revealed solitary and synergistic ef-fects. Coinfected single-cell analysis independently displayed proinflammatory phenotypes in situ. Here, we demonstrate the first evidence of polybacterial intracellular pathogenesis in human tissues and cells—potentially influencing chronic diseases at distant sites.
Altered metabolic function induced by amyloid-beta oligomers and PSEN1-mutations in iPSC-derived astrocytes
Authors: Elsworthy R. J. , Finelli M. J. , Aqattan S. , Dunleavy C. , King M. , Ludlam A. , Allen S. L. , Prosser S. , Chen R. , Jarquin S. Martinez , Kim D. H. , Brown J. , Parri H. R. , Aldred S. , Hill E. J.
Published: August 2023

Altered energy metabolism in Alzheimer’s disease (AD) is considered a major pathological hallmark implicated in the early stages of the disease process. Astrocytes play a central role in brain homeostasis and are increasingly implicated in multiple neurodegenerative diseases. We report that astrocytes differentiated from early onset familial Alzheimer’s disease (fAD) patients or control cells treated with Amyloid β oligomers exhibit significant changes in their metabolism including glucose uptake, glutamate uptake and lactate release, with increases in oxidative and glycolytic metabolism. Furthermore, we demonstrate evidence of gliosis in fAD astrocytes in addition to a change in metabolic pathways including glutamate, purines, arginine, and the citric acid cycle. Homeostatic responses to brain activity and cellular metabolism are central to normal brain function. However, altered brain metabolism and cellular stress present significant risk factors for the onset and progression of neurodegenerative disease. This study demonstrates that fAD derived astrocytes present multiple metabolic and disease associated phenotypes early in their development suggesting that chronic alterations in fAD patient early in life that present significant risk factors for disease progression in mid-life and suggest key targets for potential diagnostic features and therapeutic agents late onset dementia in midlife.
SQANTI-SIM: a simulator of controlled transcript novelty for lrRNA-seq benchmark
Authors: Mestre-Tomás Jorge , Liu Tianyuan , Pardo-Palacios Francisco , Conesa Ana
Published: August 2023

Long-read RNA-seq has emerged as a powerful tool for transcript discovery, even in well-annotated organisms. However, assessing the accuracy of different methods in identifying annotated and novel transcripts remains a challenge. Here, we present SQANTI-SIM, a versatile utility that wraps around popular long-read simulators to allow precise management of transcript novelty based on the structural categories defined by SQANTI3. By selectively excluding specific transcripts from the reference dataset, SQANTI-SIM effectively emulates scenarios involving unannotated transcripts. Furthermore, the tool provides customizable features and supports the simulation of additional types of data, representing the first multi-omics simulation tool for the lrRNA-seq field. We demonstrate the effectiveness of SQANTI-SIM by benchmarking five transcriptome reconstruction pipelines using the simulated data.
Cell free expression in proteinosomes prepared from native protein-PNIPAAm conjugates
Authors: Gao Mengfei , Wang Dishi , Leng Weihua , Wilsch-Bräuninger Michaela , Schulte Jonathan , Morgner Nina , Appelhans Dietmar , Tang T-Y. Dora
Published: August 2023

Towards the goal of building synthetic cells from the bottom-up, the establishment of micrometer-sized compartments that contain and support cell free transcription and translation that couple cellular structure to function is of critical importance. Proteinosomes, formed from crosslinked cationized protein-polymer conjugates offer a promising solution to membrane-bound compartmentalisation with an open, semi-permeable membrane. Critically, to date, there have been no demonstration of cell free transcription and translation within water-in-water proteinosomes. Herein, we present a novel approach to the fabrication of proteinosomes directly from native protein-polymer (BSA-PNIPAAm) conjugates. We show that these native proteinosomes offer an excellent alternative as artificial cell chassis. Significantly, the native proteinosomes are stable under high salt conditions and can consequently support cell free transcription and translation. The native proteinosomes offer enhanced protein expression compared to proteinosomes prepared from traditional methodologies. Furthermore, we demonstrate the integration of proteinosomes into higher order cellular architectures with membrane free compartments and liposomes. The integration of bioinspired architectural elements with the central dogma is an essential building block for realizing minimal synthetic cells and is key for exploiting artificial cells in real-world applications.
Long-term hematopoietic stem cells trigger quiescence inLeishmaniaparasites
Authors: Dirkx Laura , Acker Sara Van , Nicolaes Yasmine , Cunha João Luís Reis , Ahmad Rokaya , Caljon Ben , Imamura Hideo , Ebo Didier G. , Jeffares Daniel C. , Sterckx Yann G.-J. , Maes Louis , Hendrickx Sarah , Caljon Guy
Published: August 2023

Quiescence and posttreatment relapse constitute an important therapeutic constraint across the microbiological spectrum. This study unveils thatLeishmania infantumandL. donovaniparasites rapidly enter quiescence after an estimated 4-6 divisions in both mouse and human stem cells of the bone marrow but not in macrophages as primary host cells. Quiescent amastigotes display a reduced size and evidence for a rapid evolutionary adaptation response with genetic alterations. We formally demonstrate that acquisition of a quiescent phenotype endows parasites with a capacity to survive antileishmanial treatment. Transition through quiescence also results in an increased cellular infectivity and high transmission capacity through the sand fly vector. Transcriptional profiling of quiescent and non-quiescent metabolic states identified a limited set of 26 upregulated genes that are of particular interest given their predicted involvement as regulators of cell cycle progression and of gene expression at various levels. The differential gene set constitutes a reliable source for the identification of novel markers and potential drivers of quiescence, a metabolic state bestowing parasites the capacity to escape drug treatment.
Disentangling the neural correlates of semantic and domain-general control: The roles of stimulus domain and task process
Authors: Hodgson Victoria J. , Lambon Ralph Matthew A. , Jackson Rebecca L.
Published: August 2023

Control processes are critical for the context-appropriate use of meaningful stimuli. Similar definitions have been adopted in two distinct literatures focusing on identifying the neural correlates of ‘semantic control’ and of executive control across domains (the ‘multiple demand network’). Surprisingly, despite their proposed functions varying only in relation to domain-specificity, these networks appear to differ anatomically. However, prior comparisons are confounded by variations in task design. To what extent might varying task requirements drive differences in activation patterns that are typically attributed to stimulus domain? Here, for the first time, we use functional MRI to disentangle the effects of task process and stimulus domain during cognitively demanding tasks. Participants performed an odd-one-out task requiring rule-switching, inhibition and selection processes, and ann-back working memory task, each with meaningful semantic and non-semantic stimuli, in a factorial design. Both stimulus domain and task process affected the control regions activated, indicating that task process is indeed a key factor confounding prior studies. However, core semantic control regions (left inferior frontal gyrus, left posterior temporal cortex) also showed a preference for semantic stimuli even with matched task processes, while more peripheral semantic control regions, overlapping the multiple demand network (dorsomedial prefrontal cortex, right inferior frontal gyrus), showed little preference across task or stimulus. Conversely, most multiple demand network regions were preferentially engaged for non-semantic stimuli. These results highlight the mutual importance of stimulus domain and task process in driving variation in control region engagement, both across and between semantic control and multiple demand networks.

SIGNIFICANCE STATEMENT

The flexible, context-appropriate use of concepts requires the selection, inhibition and manipulation of meaningful information. These control processes are thought to be supported by different areas for conceptual processing compared to other task domains. This proposed ‘special’ character of semantic control has important ramifications for the nature of executive control. However, prior assessments confound the presence of meaningful stimuli with the task operations performed. Here we disentangle the effects of task process and stimulus domain for the first time, finding critical effects of both factors on the pattern of activated control regions. The results enhance our understanding of the semantic control network and how it differs from and interacts with the domain-general multiple demand network, functionally characterising each control region.
Plasmodium falciparumRaf kinase inhibitor is a lipid binding protein that interacts with CDPK1 and regulates its activity in asexual blood stage
Authors: Sharma Manish , Krishnan Deepak , Negi Pooja , Rani Komal , Revikumar Amjesh , Munde Manoj , Bansal Abhisheka
Published: August 2023

Raf Kinase Inhibitor Protein (RKIP) is an important regulator of MAPK signaling pathway in multicellular eukaryotes.Plasmodium falciparumRKIP (PfRKIP) is a putative phosphatidylethanolamine binding protein (PEBP) that shares limited similarity withHomo sapiensRKIP (HsRKIP). Interestingly, critical components of MAPK pathway are not expressed in malaria parasite and the physiological function of PfRKIP remains unknown. PfRKIP is expressed throughout the asexual schizogony with maximum expression in late schizonts. Interestingly, PfRKIP and HsRKIP show pH dependent differential interaction profiles with various lipids. At physiological pH, PfRKIP show interaction with PE and lipids containing phosphorylated phosphatidylinositol group; however, HsRKIP show no interaction under the same conditions. Mutation of conserved residues in the PEBP domain of PfRKIP decreases its interaction with PI(3)P. Furthermore, our results suggest that PfRKIP leads to increase in the autophosphorylation of PfCDPK1 that leads to transphosphorylation of substrates by PfCDPK1. Using variousin vitroandin vivoexperiments we have demonstrated the interaction of PfRKIP with PfCDPK1 and have also identified key residues in PfRKIP that play important role in this interaction. Interestingly, locostatin, a specific inhibitor of mammalian RKIP increased the interaction of PfRKIP with PfCDPK1 that perhaps leads to the sequestration of PfCDPK1 in a heterodimeric complex. Importantly, treatment of malaria parasite with locostatin shows dose dependent inhibition of parasite growth. This study suggests that specific inhibitors that modify PfRKIP leading to increase in its interaction with PfCDPK1 may be designed and explored as novel anti-malarial compounds to inhibit malaria parasite growth.
Family Lexicon: using language models to encode memories of personally familiar and famous people and places in the brain
Authors: Bruera Andrea , Poesio Massimo
Published: August 2023

Knowledge about personally familiar people and places is extremely rich and varied, involving pieces of semantic information connected in unpredictable ways through past autobiographical memories. In this work we investigate whether we can capture brain processing of personally familiar people and places using subject-specific memories, after transforming them into vectorial semantic representations using language models. First we asked participants to provide us with the names of the closest people and places in their lives. Then we collected open-ended answers to a questionnaire, aimed at capturing various facets of declarative knowledge. We collected EEG data from the same participants while they were reading the names and subsequently mentally visualizing their referents. As a control set of stimuli, we also recorded evoked responses to a matched set of famous people and places. We then created original semantic representations for the individual entities using language models. For personally familiar entities, we used the text of the answers to the questionnaire. For famous entities, we employed their Wikipedia page, which reflects shared declarative knowledge about them. Through whole-scalp time-resolved and searchlight encoding analyses we found that we could capture how the brain processes one's closest people and places using person-specific answers to questionnaires, as well as famous entities. Encoding performance was significant in a large time window (200-800ms). In terms of spatio-temporal clusters, two main axes where encoding scores are significant emerged, in bilateral temporo-parietal electrodes first (200-500ms) and frontal and posterior central electrodes later (500-700ms). We also found that XLM, a contextualized language model or large language model, provided superior encoding scores when compared with a simpler static language model as word2vec. Overall, these results indicate that language models can capture subject-specific semantic representations as they are processed in the human brain, by exploiting small-scale distributional lexical data.
Doubling the resolution of fluorescence-lifetime single-molecule localization microscopy with image scanning microscopy
Authors: Radmacher Niels , Nevskyi Oleksii , Gallea José Ignacio , Thiele Jan Christoph , Gregor Ingo , Rizzoli Silvio O. , Enderlein Jörg
Published: August 2023

In this study, we integrate a single-photon detector array into a Confocal Laser Scanning Microscope (CLSM), enabling the combination of Fluorescence Life-time Single-Molecule Localization Microscopy (FL-SMLM) with Image Scanning Microscopy (ISM). This unique combination delivers a two-fold improvement in lateral localization accuracy for SMLM while maintaining its simplicity. More-over, the addition of lifetime information from our CLSM eliminates chromatic aberration, particularly crucial for achieving few-nanometer resolution in SMLM. Our approach, named Fluorescence Lifetime ISM-SMLM (FL-iSMLM), is demon-strated through direct Stochastic Optical Reconstruction Microscopy (dSTORM) and DNA Point Accumulation for Imaging in Nanoscale Topography (DNA-PAINT) experiments on fluorescently labelled cells, showcasing both resolution enhancement and fluorescence lifetime multiplexing capabilities.
The effect of gaze on EEG measures of multisensory integration in a cocktail party scenario
Authors: Ahmed Farhin , Nidiffer Aaron R. , Lalor Edmund C.
Published: August 2023

Seeing the speaker’s face greatly improves our speech comprehension in noisy environments. This is due to the brain’s ability to combine the auditory and the visual information around us, a process known as multisensory integration. Selective attention also strongly influences what we comprehend in scenarios with multiple speakers – an effect known as the cocktail-party phenomenon. However, the interaction between attention and multisensory integration is not fully understood, especially when it comes to natural, continuous speech. In a recent electroencephalography (EEG) study, we explored this issue and showed that multisensory integration is enhanced when an audiovisual speaker is attended compared to when that speaker is unattended. Here, we extend that work to investigate how this interaction varies depending on a person’s gaze behavior, which affects the quality of the visual information they have access to. To do so, we recorded EEG from 31 healthy adults as they performed selective attention tasks in several paradigms involving two concurrently presented audiovisual speakers. We then modeled how the recorded EEG related to the audio speech (envelope) of the presented speakers. Crucially, we compared two classes of model – one that assumed underlying multisensory integration (AV) versus another that assumed two independent unisensory audio and visual processes (A+V). This comparison revealed evidence of strong attentional effects on multisensory integration when participants were looking directly at the face of an audiovisual speaker. This effect was not apparent when the speaker’s face was in the peripheral vision of the participants. Overall, our findings suggest a strong influence of attention on multisensory integration when high fidelity visual (articulatory) speech information is available. More generally, this suggests that the interplay between attention and multisensory integration during natural audiovisual speech is dynamic and is adaptable based on the specific task and environment.
Climate and management changes drove more stress-tolerant and less competitive plant communities in 40 years
Authors: Bopp Marie-Charlotte , Kazakou Elena , Metay Aurélie , Maillet Jacques , Quidoz Marie-Claude , Genty Léa , Fried Guillaume
Published: August 2023

Spontaneous plant communities have undergone considerable constraints due to human-mediated changes. Understanding how plant communities are shifting in response to land management and climate changes is necessary to predict future ecosystem functioning and improve the resilience of managed ecosystems, such as agroecosystems. Using Mediterranean weed communities as models of managed plant communities in a climate change hotspot, we quantified to which extent they have shifted from the 1980s to the 2020s in response to climate and management changes in vineyards. In four decades, the annual range of temperatures (i.e.the difference between the warmest month’s and the coldest month’s mean temperatures) increased by 1.2°C and the summer temperatures by 2°C. Weed management diversified over time with the adoption of mowing that replaced the chemical weeding of inter-rows. Current weed communities were 41% more abundant, 24% more diverse and with a less even distribution of abundance across species than the 1980s communities at the vineyard level. Modern communities were composed of more annual species (57% of annual species in the 1980s versus 80% in the 2020s) with lower lateral spreadability and seed mass and were composed of fewer C4 species. They had higher community-weighted specific leaf area, higher leaf dry matter content and lower leaf area than 1980s weed communities. At the community level, the onset of flowering was earlier and the duration of flowering was longer in the 2020s. Climate change induced more stress-tolerant communities in the 2020s while the diversification of weed management practices over time filtered less competitive communities. This study shows that plant communities are adapting to climate change and that land management is a strong lever for action to model more diverse and functional plant communities in the future.
Intra- and interspecific variations in genome sizes ofAgariciacorals from Curaçao
Authors: Rañises Dina Mae L. , Gonzalez Maria Juliana Vanegas , Tawfeeq Mohammed M. , Gaudray Florence Rodriguez , Malay Maria Celia (Machel) D. , Vermeij Mark , Flot Jean-François
Published: August 2023

Genome size is a fundamental biological trait that is known to exhibit high diversity among eukaryotic species, but its intraspecific diversity has only scarcely been studied to date. In scleractinian corals, genome size data are only available for a few species. In this study, intra- and interspecific variations in genome size of the coral genusAgariciacollected from Curaçao were investigated. Morphology was congruent with genetic analyses of the nuclear markers internal transcribed spacer 2 (ITS2) and L-threonine 3-dehydrogenase (TDH) in delimiting threeAgariciaspecies among our samples. A refined Feulgen Image Analysis Densitometry (FIAD) protocol yielded genome sizes that ranged from 0.359 pg to 0.593 pg within this genus (a 1.7-fold range). The highest intraspecific variation in genome size was recorded in the depth-generalistA. lamarcki(1.5-fold range), followed by the depth specialistA. humilis(1.4-fold range) andA. agaricites(1.3-fold range), the species with an intermediate depth distribution. The mean genome size ofA. agaricites(0.495 pg) was significantly larger than that ofA. lamarcki(0.448 pg) andA. humilis(0.434 pg). No correlation between average genome size and nucleotide polymorphismπwas detected, but we found an almost linear correlation between intraspecific variance of genome size andπof ITS2 (Pearson’s r = 0.984, p = 0.113). Genome size and collection depths of bothA. lamarcki(Pearson’s r = 0.328, p = 0.058) andA. agaricites(Pearson’s r = -0.270, p = 0.221) were also not significantly associated. To our knowledge, this study provides the first account of intraspecific variation in corals; the apparent correlation detected between the nucleotide polymorphism of a species and the variance of its genome size will have to be tested using a larger taxonomic spectrum of scleractinian corals as well as in other groups of animals.
Thermodynamic profiles for co-translational trigger factor function
Authors: Herling Therese W. , Cassaignau Anaïs M. E. , Wentink Anne S. , Peter Quentin A. E. , Kumar Pavan C. , Kartanas Tadas , Schneider Matthias M. , Cabrita Lisa D. , Christodoulou John , Knowles Tuomas P. J.
Published: August 2023

Molecular chaperones are central to the maintenance of proteostasis in living cells. A key member of this protein family is trigger factor (TF), which acts throughout the protein lifecycle and has a ubiquitous role as the first chaperone encountered by proteins during synthesis. However, our understanding of how TF achieves favourable interactions with such a diverse substrate base remains limited. Here, we use microfluidics to reveal the thermodynamic determinants of this process. We find that TF binding to empty 70S ribosomes is enthalpydriven, with micromolar affinity, while nanomolar affinity is achieved through a favourable entropic contribution for both intrinsically disordered and folding competent nascent chains. These findings suggest a general mechanism for co-translational TF function, which relies on occupation of the exposed TF substrate-binding groove, rather than specific complementarity between chaperone and RNC. These insights add to our wider understanding of how proteins can achieve broad substrate specificity.
Broad-spectrum antiviral activity of clinically approved CYP3A inhibitors against pathogenic human coronaviruses in vitro
Authors: Gallucci Lara , Bazire James , Davidson Andrew D , Shytaj Iart Luca
Published: August 2023

Coronaviruses pose a permanent risk of outbreaks, with three highly pathogenic species and strains (SARS-CoV, MERS-CoV, SARS-CoV-2) having emerged in the last twenty years. Limited antiviral therapies are currently available and their efficacy in randomized clinical trials enrolling SARS-CoV-2 patients has not been consistent, highlighting the need for more potent treatments. We previously showed that cobicistat, a clinically approved inhibitor of Cytochrome P450-3A (CYP3A), has direct antiviral activity against early circulating SARS-CoV-2 strainsin vitroand in Syrian hamsters. Cobicistat is a derivative of ritonavir, which is co-administered as pharmacoenhancer with the SARS-CoV-2 protease inhibitor nirmatrelvir, to inhibit its metabolization by CPY3A and preserve its antiviral efficacy. Here, we used automated imaging and analysis for a screening and parallel comparison of the anti-coronavirus effects of cobicistat and ritonavir. Our data show that both drugs display antiviral activity at low micromolar concentrations against multiple SARS-CoV-2 variantsin vitro, including epidemiologically relevant Omicron subvariants. Despite their close structural similarity, we found that cobicistat is more potent than ritonavir, as shown by significantly lower EC50 values in monotherapy and higher levels of viral suppression when used in combination with nirmatrelvir. Finally, we show that the antiviral activity of both cobicistat and ritonavir is maintained against other human coronaviruses, including HCoV-229E and the highly pathogenic MERS-CoV. Overall, our results demonstrate that cobicistat has more potent anti-coronavirus activity than ritonavir and suggest that dose adjustments could pave the way to the use of both drugs as broad-spectrum antivirals against highly pathogenic human coronaviruses.
Harnessing Agent-Based Modeling in CellAgentChat to Unravel Cell-Cell Interactions from Single-Cell Data
Authors: Raghavan Vishvak , Li Yue , Ding Jun
Published: August 2023

Understanding cell-cell interactions (CCIs) is essential yet challenging due to the inherent intricacy and diversity of cellular dynamics. Existing approaches often analyze global patterns of CCIs using statistical frameworks, missing the nuances of individual cell behavior due to their focus on aggregate data. This makes them insensitive in complex environments where the detailed dynamics of cell interactions matter. We introduce CellAgentChat, an agent-based model (ABM) designed to decipher CCIs from single-cell RNA sequencing and spatial transcriptomics data. This approach models biological systems as collections of autonomous agents governed by biologically inspired principles and rules. Validated against seven diverse single-cell datasets, CellAgentChat demonstrates its effectiveness in detecting intricate signaling events across different cell populations. Moreover, CellAgentChat offers the ability to generate animated visualizations of single-cell interactions and provides flexibility in modifying agent behavior rules, facilitating thorough exploration of both close and distant cellular communications. Furthermore, CellAgentChat leverages ABM features to enable intuitive in silico perturbations via agent rule modifications, pioneering new avenues for innovative intervention strategies. This ABM method empowers an in-depth understanding of cellular signaling interactions across various biological contexts, thereby enhancing in-silico studies for cellular communication-based therapies.
Clinical investigations to evaluate high-risk orthopaedic devices: systematic review of the peer-reviewed medical literature
Authors: Lübbeke Anne , Combescure Christophe , Barea Christophe , Gonzalez Amanda Inez , Tucker Keith , Kjærsgaard-Andersen Per , Melvin Tom , Fraser Alan G , Nelissen Rob , Smith James A
Published: August 2023

Purpose

The objective of this systematic review was to give an overview of clinical investigations regarding hip and knee arthroplasty implants published in peer-reviewed scientific medical journals before entry into force of the EU Medical Device Regulation in May 2021.

Methods

We systematically reviewed the medical literature for a random selection of hip and knee implants, to identify all peer-reviewed clinical investigations published within 10years before and up to 20years after regulatory approval. We report study characteristics, methodologies, outcomes, measures to prevent bias, and timing of clinical investigations, of 30 current implants. The review process was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results

We identified 2912 publications and finally included 151 papers published between 1995 and 2021 (63 on hip stems, 34 on hip cups, 54 on knee systems). We identified no clinical studies published before CE-marking for any selected device, and no studies even up to 20 years after CE-marking in one quarter of devices. There were very few randomized controlled trials, and registry-based studies generally had larger sample sizes and better methodology.

Conclusions

The peer-reviewed literature alone is insufficient as source of clinical investigations of these high-risk devices intended for life-long use. A more systematic, efficient and faster way to evaluating safety and performance is necessary. Using a phased introduction approach, nesting comparative studies of observational and experimental design in existing registries, increasing use of benefit measures, and accelerating surrogate outcomes research, will help to minimise risks and maximise benefits.
Distinct COVID-19 vaccine combinations result in divergent immune responses
Authors: Zaeck Luca M. , Tan Ngoc H. , Rietdijk Wim J.R. , Geers Daryl , Sablerolles Roos S.G. , Bogers Susanne , van Dijk Laura L.A. , Gommers Lennert , van Leeuwen Leanne P.M. , Rugebregt Sharona , Goorhuis Abraham , Postma Douwe F. , Visser Leo G. , Dalm Virgil A.S.H. , Lafeber Melvin , Kootstra Neeltje A. , Huckriede Anke L.W. , Haagmans Bart L. , van Baarle Debbie , Koopmans Marion P.G. , van der Kuy P. Hugo M. , GeurtsvanKessel Corine H. , de Vries Rory D. ,   SWITCH-ON Research Group
Published: August 2023

Waning antibody responses after COVID-19 vaccination combined with the emergence of the SARS-CoV-2 Omicron lineage led to reduced vaccine effectiveness. As a countermeasure, bivalent mRNA-based booster vaccines encoding the ancestral spike protein in combination with that of Omicron BA.1 or BA.5 were introduced. Since then, BA.2-descendent lineages have become dominant, such as XBB.1.5 or BA.2.86. Here, we assessed how different COVID-19 priming regimens affect the immunogenicity of the recently used bivalent booster vaccinations and breakthrough infections. BA.1 and BA.5 bivalent vaccines boosted neutralizing antibodies and T-cells up to 3 months after boost; however, cross-neutralization of XBB.1.5 was poor. Interestingly, different combinations of prime-boost regimens induced divergent responses: participants primed with Ad26.COV2.S developed lower binding antibody levels after bivalent boost while neutralization and T-cell responses were similar to mRNA-based primed participants. In contrast, the breadth of neutralization was higher in mRNA-primed and bivalent BA.5 boosted participants. Combined, we highlight important ‘lessons learned’ from the employed COVID-19 vaccination strategies. Our data further support the use of monovalent vaccines based on circulating strains when vaccinating risk groups, as recently recommended by the WHO. We emphasize the importance of the continuous assessment of immune responses targeting circulating variants to guide future COVID-19 vaccination policies.
Experimental and computational study of imidazole-pyridine and its derivatives as corrosion inhibitors on brass in sulfuric acid solution
Authors: Zhou Xin , Zhou Wenbin , Zhang Yang Zheng , Li Meng-Ran , Sun Haijing , Sun Jie
Published: August 2023

Purpose

This paper aims to study the corrosion inhibition behavior of imidazopyridine and its three derivatives on brass.

Design/methodology/approach

The authors performed weight loss experiments, electrochemical experiments including the polarization curve and electrochemical impedance spectrum, corrosion morphology observation using scanning electron microscope (SEM) and atomic force microscope (AFM) and surface composition analysis via X-ray photoelectron spectroscopy (XPS) to analyze the corrosion inhibition behavior of imidazopyridine and its three derivatives on brass by using quantum chemical calculation (Gaussian 09), molecular dynamics simulation (M-S) and Langmuir adsorption isotherm.

Findings

According to the results, imidazole-pyridine and its derivatives were found to be modest or moderately mixed corrosion inhibitors; moreover, they were spontaneously adsorbed on the metal surface in a single-layer, mixed adsorption mode.

Originality/value

The corrosion inhibition properties of pyrazolo-[1,2-a]pyridine and its derivatives on brass in sulfuric acid solution were analyzed through weight loss and electrochemical experiments. Moreover, SEM and AFM were simultaneously used to observe the corrosion appearance. Furthermore, XPS was used to analyze the surface. Then, Gaussian 09 and M-S were combined along with the Langmuir adsorption isotherm to investigate the corrosion inhibition mechanism of imidazole-[1,2-a]pyridine and its derivatives.
On the field uniformity of reverberation chambers – a global sensitivity analysis study
Authors: Kenderes Anett , Gyimóthy Szabolcs , Benkő Péter Tamás
Published: August 2023

Purpose

Global sensitivity analysis (SA) by means of Sobol’ indices enhanced with different surrogate modeling techniques is performed in this work. The purpose is to investigate the influence of measurement uncertainties and the environment characteristics themselves on the desired field uniformity in reverberation chambers (RCs). This yields an efficient apparatus for the stirring and chamber design process.

Design/methodology/approach

The technique of Sobol’ indices, as a candidate of global SA methods, is suitable for high fluctuations due to its robustness, which can be addressed to the stochastic nature of the RC environment. The aim of using surrogate modeling techniques is to compute the indices efficiently with a moderate number of required simulations. The powerfulness of this approach is introduced in a simple numerical example in which the physical phenomena can be identified more straightforwardly.

Findings

This method can provide useful knowledge in the lower frequency range, where the ideal properties of the electromagnetic field in RCs cannot be established, and the importance of the setup parameters can vary from configuration to configuration. In addition, it can serve as a basis for setup adaptation during parallelized electromagnetic compatibility tests, which would result in a more time- and cost-saving option in industrial applications in the future.

Originality/value

Despite the previous attempts, a profound investigation of multiple setup parameters is still a hot topic. The main contribution of this work is the extension of the application area of the method of Sobol’ indices to RCs, which has not been done so far.
What is the connection between Fintechs’ video marketing and their vulnerable customers’ brand engagement during crises?
Authors: Sakas Damianos P. , Giannakopoulos Nikolaos T. , Terzi Marina C. , Kamperos Ioannis Dimitrios G. , Kanellos Nikos
Published: August 2023

Purpose

The paper’s main goal is to examine the relationship between the video marketing of financial technologies (Fintechs) and their vulnerable website customers’ brand engagement in the ongoing coronavirus disease 2019 (COVID-19) crisis.

Design/methodology/approach

To extract the required outcomes, the authors gathered data from the five biggest Fintech websites and YouTube channels, performed multiple linear regression models and developed a hybrid (agent-based and dynamic) model to assess the performance connection between their video marketing analytics and vulnerable website customers’ brand engagement.

Findings

It has been found that video marketing analytics of Fintechs’ YouTube channels are a decisive factor in impacting their vulnerable website customers’ brand engagement and awareness.

Research limitations/implications

By enhancing video marketing analytics of their YouTube channels, Fintechs can achieve greater levels of vulnerable website customers’ engagement and awareness. Higher levels of vulnerable customers’ brand engagement and awareness tend to decrease their vulnerability by enhancing their financial knowledge and confidence.

Practical implications

Fintechs should aim to increase the number of total videos on their YouTube channels and provide videos that promote their customers’ knowledge of their services to increase their brand engagement and awareness, thus reducing their vulnerability. Moreover, Fintechs should be aware not to over-post videos because they will be in an unfavorable position against their competitors.

Originality/value

This research offers valuable insights regarding the importance of video marketing strategies for Fintechs in promoting their vulnerable website customers’ brand awareness during crisis periods.
Comparative approach in public health social security: a legal case study of the Indonesian, France, and Singapore health systems
Authors: Paluttri Sukri
Published: August 2023

Purpose

This research paper aimed to study the legal structure of top-performing health governance systems and compare them with the Indonesian health social security system to identify the main differences and provide recommendations for Indonesian and other developing countries’ health policymakers and administrators.

Design/methodology/approach

Using formative research with a conceptual approach and statute approach as method in this study. Data was gathered using the document study technique, which studies various documents, especially legal documents related to health law, linked to legal purpose theories. Moreover, the World Health Organization ranking was considered to choose the two countries (France and Singapore) with a high social health security system for comparative analysis. All data collected has been analyzed using a qualitative and theoretical basis. Content analysis was performed by analyzing the legal documents, and the regulatory framework of all three countries was deeply analyzed to draw conclusions and recommendations.

Findings

Indonesia has specific laws to implement a social security system in the health sector. However, the lack of the best medical facilities and infrastructure and weak implementation of existing laws were identified as major reasons behind the poor health security system compared to comparative countries. Also, as a developing nation Indonesian Government face budgetary pressures and huge population challenges to meet required standards. Thus, the financing approaches used by Singapore and France may help developing countries meet these challenges effectively. Therefore, there is a dire need to strengthen the social health security system all over the country with amendments to laws and ensure the implementation of prevailing laws and regulations.

Practical implications

Providing understanding related to the social security health system in Indonesia along with a detailed description of the sound social health security system in France and Singapore will further provide an avenue for the researchers to critically analyze this line of study to devise some valuable suggestions further and to draw loopholes in the system.

Originality/value

A comparative approach for legal studies in the health sector is rare. So, this research advanced the social security health system-related literature and legal studies on the health sector by using this comparative approach to develop policy insights and future research directions, which will further help the field to grow.