bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies on Human-Coronavirus protein-protein interaction network from the perspective of viral adaptation in a novel host
Authors: Acharya Debarun , Dutta Tapan K
Published: January 2024

Host-pathogen interaction is the best example of an evolutionary arms race where pathogen and host continuously coevolve to survive and exert negative effects on each other. The adaptability of both host and pathogen is critical for this association. In this study, we explored the adaptation of the severe acute respiratory syndrome (SARS) coronavirus (CoV) in humans from the genomic and evolutionary perspectives based on a comparative analysis of SARS-CoV2-human and Other-CoV-human interactions. We observed that human proteins that are part of the SARS-CoV2-human association are less enriched in hubs and bottlenecks. Again, they also take part in fewer protein complexes and show faster evolutionary rates compared to the Other-CoV-associated human proteins. The human proteins involved in the interaction with SARS-CoV2 are mostly longer proteins harboring long disordered stretches and a higher level of disordered protein binding sites. Codon usage analysis also revealed that the novel coronavirus is least adapted to codons, used in housekeeping genes and genes that get expressed in lung tissues, compared to other two deadly coronaviruses, SARS CoV1 and MERS CoV. We conclude that the signatures showed by SARS-CoV2-human protein interaction network represent a model for understanding the evolutionary feature of an early stage of host-virus association in comparison to that obtained from relatively long-term-associated host-virus interactions, achieving higher levels of adaptation.

Importance

The current study focuses on the evolution of viruses, using novel coronavirus as a model. The host-pathogen interaction is better viewed from molecular perspective, where host and pathogen proteins interact and co-evolve with each other. This is even more important for viruses, which use the host’s cellular machinery for protein synthesis. As for a deadly virus, killing the host is inadvertent as it is also suicidal for the virus itself. A more stable association that is beneficial for both host and virus will require host adaptation, achievable through evolutionary time. In this study, the deadly novel human coronavirus has been viewed as the early stage of host viral interaction, which has been achieved through a more random way, with lower adaptation to host codons compared to the other human coronaviruses, having more stable host-association for being evolutionarily older.
Targeted Perturb-seq Reveals EGR1 and FOS as Key Regulators of the Transcriptional RAF-MAPK Response
Authors: Kassem Ghanem El , Sieber Anja , Klinger Bertram , Uhlitz Florian , Steinbrecht David , van Bentum Mirjam , Hillmer Jasmine , von Schlichting Jennifer , Schäfer Reinhold , Blüthgen Nils , Boettcher Michael
Published: January 2024

The MAPK pathway is an important cellular signaling cascade whose dysregulation causes a variety of diseases. While the upstream regulators of this cascade have been extensively characterized, the understanding of how its activation translates into different transcriptional responses remains poorly understood. This study attempts to fill this knowledge gap by using targeted Perturb-seq against 22 transcription factors in an inducible model system for RAF-MAPK signaling. A topology-based modeling approach is applied to the obtained data to construct a directional interaction network. By removing coherent feed-forward loops and integrating the expression kinetics of transcription factors, a parsimonious network structure is derived that distinguishes direct from indirect interactions between the investigated transcription factors and their targets. In particular, EGR1 and FOS are found to act as orthogonal upstream regulators of the RAF-MAPK response. The results presented here provide valuable insights into the organization of the transcriptional network downstream of RAF-MAPK signaling and thus provide a basis for a better understanding of this complex process.
Urban sensory conditions alter rival interactions and mate choice in urban and forest túngara frogs
Authors: Smit Judith A.H. , Thijssen Vera , Cronin Andrew D. , Ellers Jacintha , Halfwerk Wouter
Published: January 2024

Sexual communication often takes place in networks with multiple competing signalers being simultaneously assessed by mate choosers. Altered sensory conditions, such as noise and light pollution, can affect communication by altering signal production and perception. While evidence of sensory pollution affecting sexual signaling is widespread, few studies assess impacts on sexual signaling during rival interactions as well as mate choice, let alone whether urban and forest populations have diverged in their response. Here, we investigate the effects of urban sensory conditions on sexual communication in urban and forest túngara frogs (Engystomops pustulosus). We recorded dyadic vocal rival interactions and assessed mate choice with and without noise and light pollution in the lab. We show that urban sensory conditions can directly impact the intensity of rival interactions, differences between rivals and mate choice, though changes were often in opposite directions for frogs of urban and forest origins. Moreover, we demonstrate that changes in rival interactions in response to light and noise pollution can also indirectly affect how females choose between potential mates. Our study reveals origin-dependent direct and indirect effects of noise and light pollution, which ultimately translate into fitness consequences for sexual communication in urban populations.
Resource-explicit interactions in spatial population models
Authors: Champer Samuel E. , Chae Bryan , Haller Benjamin C. , Champer Jackson , Messer Philipp W.
Published: January 2024

Continuous-space population models can yield significantly different results from their panmictic counterparts when assessing evolutionary, ecological, or population-genetic processes. However, the computational burden of spatial models is typically much greater than that of panmictic models due to the overhead of determining which individuals interact with one another and how strongly they interact. Though these calculations are necessary to model local competition that regulates the population density, they can lead to prohibitively long runtimes. Here, we present a novel modeling method in which the resources available to a population are abstractly represented as an additional layer of the simulation. Instead of interacting directly with one another, individuals interact indirectly via this resource layer. We find that this method closely matches other spatial models, yet can dramatically increase the speed of the model, allowing the simulation of much larger populations. Additionally, models structured in this manner exhibit other desirable characteristics, including more realistic spatial dynamics near the edge of the simulated area, and an efficient route for modeling more complex heterogeneous landscapes.
Genetic Associations of Lipid-Lowering Drugs and Parkinson’s Disease: A Mendelian Randomization Study
Authors: Shen Lin , Yang Yifan , Li Yi , Chin Hok Leong , Huang Helen , Cheung Bernard Man Yung , Tse Gary , Chou Oscar Hou In , Zhou Jiandong
Published: January 2024

Background

There is a need to establish the role of lipid-lowering agents as a therapeutic option for Parkinson’s Disease (PD), but its associations remain elusive. This study investigated genetic variants proxying lipid-lowering agents through HMGCR, NPC1L1, and PCSK9 inhibitors to determine casual associations with PD risk.

Methods

We utilized a two-sample Mendelian randomization (MR) framework, where low-density lipoprotein (LDL) was the outcome of interest. Genetic associations with LDL were extracted from the Global Lipids Genetics Consortium. Summary statistics for PD were extracted from two GWAS datasets, consistent of 1,843 PD cases and 216,630 control in the first dataset and 1,570 PD cases and 1,259 controls in the second dataset. Instrumental variables (IV) were optimized with positive control analyses on cardiovascular and metabolic outcomes. IV-exposure associations from LDL GWAS data were integrated with IV-outcome associations from the PD GWAS data. The inverse variance weighted method was applied. Bayesian colocalization analysis identified target gene regions for LDL and PD.

Results

Genetic variations inHMGCRwere significantly associated with a reduced risk of PD (odds ratio [OR] = 0.54, 95% CI 0.34-0.86). However, variation inHMGCRwas associated with an increased risk of the tremor-dominant (TD) subtype compared to the postural instability/gait difficulty (PIGD) subtype (OR = 8.43, 95% CI 2.12-33.52). There were trends with increased risk for the TD subtype inNPC1L1and a decreased risk inPCSK9but these findings did not meet the Bonferroni threshold. We identified two single nucleotide polymorphisms (SNPs) inHMGCRwithin the same genomic region of close proximity, with rs12916 as the leading SNP associated with LDL and rs10942735 as the leading SNP associated with PD.

Conclusion

A casual association betweenHMGCRinhibition and reduced overall PD risk was identified, but there were increased the risks of tremor-dominant subtypes.
The Optimization of a Natural Language Processing Approach for the Automatic Detection of Alzheimer’s Disease Using GPT Embeddings
Authors: Runde Benjamin S. , Alapati Ajit , Bazan Nicolas G.
Published: January 2024

As the impact of Alzheimer’s disease (AD) is projected to grow in the coming decades as the world’s population ages, the development of noninvasive and cost-effective methods of detecting AD is essential for the early prevention and mitigation of the progressive disease, alleviating its expected global impact. This study analyzes audio processing techniques and transcription methodologies to optimize the detection of AD through the natural language processing (NLP) of spontaneous speech. We enhanced audio fidelity using Boll Spectral Subtraction and evaluated the transcription accuracy of state-of-the-art AI services—locally-based Wav2Vec and Whisper, alongside cloud-based IBM Cloud and Rev AI—against traditional manual transcription methods. The choice between local and cloud-based solutions hinges on a trade-off between privacy, ongoing costs, and computational requirements. Leveraging OpenAI’s GPT for word embeddings, we enhanced the training of Support Vector Machine (SVM) classifiers, which were crucial in analyzing transcripts and refining detection accuracy. Our findings reveal that AI-driven transcriptions significantly outperform manual counterparts when classifying AD and Control samples, with Wav2Vec using enhanced audio exhibiting the highest accuracy and F-1 scores (0.99 for both metrics) for locally based systems and Rev AI using unenhanced audio leading cloud-based methods with comparable precision (0.96 for both metrics). The study also uncovers the detrimental effect of including interviewer speech in recordings on model performance, advocating for the exclusion of such interactions to improve data quality for AD classification algorithms. Our comprehensive evaluation demonstrates that AI transcription (both Cloud and Local) and NLP technologies in their current forms can classify AD, as well as probable AD and mild cognitive impairment (MCI), a prodromal stage of AD, accurately but suffer from a lack of available training data. The insights garnered from this research lay the groundwork for future advancements in the noninvasive monitoring and early detection of cognitive impairments through linguistic analysis.
Metagenomics insights into microbial diversity shifts among seagrass sediments
Authors: Detcharoen Matsapume , Rattanachot Ekkalak , Prathep Anchana
Published: January 2024

Seagrasses are important in marine ecosystems by providing food and shelter for animals, storing carbon, and reducing sulfide and methane emissions. Previous studies found variations in the microbiomes of seagrass both above and below sediment surface, with certain microbes serving as indicators of seagrass health. Despite numerous studies on bacterial communities in specific seagrass species, little is known about bacterial communities in mixed seagrass beds. This study used metagenomics to investigate microbial diversity in bare and seagrass-associated sediments, across seven seagrass species combinations. The findings revealed higher alpha diversity of bacteria and archaea in the upper layers, whereas microbial eukaryotes were more diverse in the lower layers. Significant taxonomic differences were found between bare and seagrass sediments, and among seagrass species. Several metagenome-assembled genomes were reconstructed, primarily from Pseudomonadota and Thermodesulfobacteriota. This study improves our understanding of complex interactions between seagrasses and their associated microbial communities and laying a foundation for efficient strategies for the management and restoration of seagrass ecosystems.
Neonatal sensitivity to vocal emotions: A developmental change at 37 weeks of gestational age
Authors: Hou Xinlin , Zhang Peng , Mo Licheng , Peng Cheng , Zhang Dandan
Published: January 2024

Emotional responsiveness in neonates, particularly their ability to discern vocal emotions, plays an evolutionarily adaptive role in human communication and adaptive behaviors. The developmental trajectory of emotional sensitivity in neonates is crucial for understanding the foundations of early social-emotional functioning. However, the precise onset of this sensitivity and its relationship with gestational age (GA) remain subjects of investigation. In a study involving 120 healthy neonates categorized into six groups based on their GA (ranging from 35 and 40 weeks), we explored their emotional responses to vocal stimuli. These stimuli encompassed disyllables with happy and neutral prosodies, alongside acoustically matched nonvocal control sounds. The assessments occurred during natural sleep states using the odd-ball paradigm and event-related potentials. The results reveal a distinct developmental change at 37 weeks GA, marking the point at which neonates exhibit heightened perceptual acuity for emotional vocal expressions. This newfound ability is substantiated by the presence of the mismatch response, akin to an initial form of adult mismatch negativity, elicited in response to positive emotional vocal prosody. Notably, this perceptual shift’s specificity becomes evident when no such discrimination is observed in acoustically matched control sounds. Neonates born before 37 weeks GA do not display this level of discrimination ability. This developmental change has important implications for our understanding of early social-emotional development, highlighting the role of gestational age in shaping early perceptual abilities. Moreover, while these findings introduce the potential for a valuable screening tool for conditions like autism, characterized by atypical social-emotional functions, it is important to note that the current data are not yet robust enough to fully support this application. This study makes a substantial contribution to the broader field of developmental neuroscience and holds promise for future research on early intervention in neurodevelopmental disorders.

Significance statement

This study illuminates a key developmental change, pinpointing the emergence of heightened emotional perceptual acuity at 37 weeks of gestational age. Employing rigorous methods, we reveal that neonates at this stage exhibit remarkable discrimination abilities for emotional vocal prosody, a vital turning point in early social-emotional functioning. These findings emphasize the pivotal role of gestational age in shaping neonatal perception and provides a potential pathway for early screening of neurodevelopmental disorders, particularly autism. This insight holds profound implications for understanding the foundations of early social-emotional development in humans, offering a potential tool for early intervention in neurodevelopmental disorders, thereby enhancing child health and well-being.
Comprehensive benchmark of differential transcript usage analysis for static and dynamic conditions
Authors: Lio Chit Tong , Düz Tolga , Hoffmann Markus , Willruth Lina-Liv , Baumbach Jan , List Markus , Tsoy Olga
Published: January 2024

RNA sequencing offers unique insights into transcriptome diversity, and a plethora of tools have been developed to analyze alternative splicing. One important task is to detect changes in the relative transcript abundance in differential transcript usage (DTU) analysis. The choice of the right analysis tool is non-trivial and depends on experimental factors such as the availability of single- or paired-end and bulk or single-cell data. To help users select the most promising tool for their task, we performed a comprehensive benchmark of DTU detection tools. We cover a wide array of experimental settings, using simulated bulk and single-cell RNA-seq data as well as real transcriptomics datasets, including time-series data. Our results suggest that DEXSeq, edgeR, and LimmaDS are better choices for paired-end data, while DSGseq and DEXSeq can be used for single-end data. In single-cell simulation settings, we showed that satuRn performs better than DTUrtle. In addition, we showed that Spycone is optimal for time series DTU/IS analysis based on the evidence provided using GO terms enrichment analysis.
Intestinal helminth infection impairs vaccine-induced T cell responses and protection against SARS-CoV-2
Authors: Desai Pritesh , Karl Courtney E. , Ying Baoling , Liang Chieh-Yu , Garcia-Salum Tamara , Santana Ana Carolina , Caten Felipe Ten , Urban Joseph F. , Elbashir Sayda M. , Edwards Darin K. , Ribeiro Susan P. , Thackray Larissa B. , Sekaly Rafick P. , Diamond Michael S.
Published: January 2024

Although vaccines have reduced COVID-19 disease burden, their efficacy in helminth infection endemic areas is not well characterized. We evaluated the impact of infection byHeligmosomoides polygyrus bakeri(Hpb), a murine intestinal hookworm, on the efficacy of an mRNA vaccine targeting the Wuhan-1 spike protein of SARS-CoV-2. Although immunization generated similar B cell responses in Hpb-infected and uninfected mice, polyfunctional CD4+and CD8+T cell responses were markedly reduced in Hpb-infected mice. Hpb-infected and mRNA vaccinated mice were protected against the ancestral SARS-CoV-2 strain WA1/2020, but control of lung infection was diminished against an Omicron variant compared to animals immunized without Hpb infection. Helminth mediated suppression of spike-specific CD8+T cell responses occurred independently of STAT6 signaling, whereas blockade of IL-10 rescued vaccine-induced CD8+T cell responses. In mice, intestinal helminth infection impairs vaccine induced T cell responses via an IL-10 pathway and compromises protection against antigenically shifted SARS-CoV-2 variants.
Timing of Regadenoson-induced Peak Hyperemia and the Effects on Coronary Flow Reserve
Authors: Kattapuram Nathan , Shadman Shahrad , Morgan Eric E. , Benton Charles , Awojoodu Stacian , Kim Dong-Yun , Ramos Joao , Barac Ana , Bandettini W. Patricia , Kellman Peter , Weissman Gaby , Carlsson Marcus
Published: January 2024

Background

Regadenoson is used to induce hyperemia in cardiac imaging, facilitating diagnosis of ischemia and assessment of coronary flow reserve (CFR). While the regadenoson package insert recommends administration of radionuclide tracer 10-20 seconds after injection, peak hyperemia has been observed at approximately 100 seconds after injection in healthy volunteers undergoing cardiovascular magnetic resonance imaging (CMR). It is unclear when peak hyperemia occurs in a patient population.

Objectives

The goal of this study was to determine time to peak hyperemia after regadenoson injection in healthy volunteers and patients, and whether the recommended image timing in the package insert underestimates CFR.

Methods

Healthy volunteers (n=15) and patients (n=25) underwent stress CMR, including phase-contrast imaging of the coronary sinus at rest and multiple timepoints after 0.4 mg regadenoson injection. Coronary sinus flow (ml/min) was divided by resting values to yield CFR. Smoothed, time-resolved curves for CFR were generated with pointwise 95% confidence intervals.

Results

CFR between 60 and 120 seconds was significantly higher than CFR at 30 seconds after regadenoson injection (p < 0.05) as shown by non-overlapping 95% confidence intervals for both healthy volunteers (30 s, [2.8, 3.4]; 60 s, [3.8, 4.4]; 90 s, [4.1, 4.7]; 120 s, [3.6, 4.3]) and patients (30 s, [2.1, 2.5]; 60 s, [2.6, 3.1]; 90 s, [2.7, 3.2]; 120 s, [2.5, 3.1]).

Conclusion

Imaging at 90 seconds following regadenoson injection is the optimal approach to capture peak hyperemia. Imaging at 30 seconds, which is more aligned with the package insert recommendation, would yield an underestimate of CFR and confound assessment of microvascular dysfunction.
Pathways linking physical and mental health: The role of brain structure and environment
Authors: Tian Ye Ella , Cole James H , Bullmore Edward T , Zalesky Andrew
Published: January 2024

Depression and anxiety are prevalent in people with a chronic physical illness. Increasing evidence suggests that co-occurring physical and mental illness is associated with shared biological pathways. However, little is known about the brain’s role in mediating links between physical and mental health. Using multimodal brain imaging and organ-specific physiological markers from the UK Biobank, we establish prospective associations between the baseline health of seven body organs and mental health outcomes at 4-14 years follow-up, focussing on depression and anxiety. We reveal multiple pathways, mediated by the brain, through which poor organ health may lead to poor mental health. We identify several lifestyle factors that influence mental health through their selective impact on the physiology of specific organ systems and brain structure. Our work reveals the interplay between brain, body and lifestyle and their collective influence on mental health. Pathways elucidated here may inform behavioral interventions to mitigate or prevent the synergistic co-occurrence of physical and mental disorders.
Functional connectivity of stimulus-evoked brain responses to natural speech in post-stroke aphasia
Authors: Mehraram Ramtin , Clercq Pieter De , Kries Jill , Vandermosten Maaike , Francart Tom
Published: January 2024

One out of three stroke-patients develop language processing impairment known as aphasia. The need for ecological validity of the existing diagnostic tools motivates research on biomarkers, such as stimulus-evoked brain responses. With the aim of enhancing the physiological interpretation of the latter, we used EEG to investigate how functional brain network patterns associated with the neural response to natural speech are affected in persons with post-stroke chronic aphasia.

EEG was recorded from 24 healthy controls and 40 persons with aphasia while they listened to a story. Stimulus-evoked brain responses at all scalp regions were measured as neural envelope tracking in the delta (0.5-4 Hz), theta (4-8 Hz) and low-gamma bands (30-49 Hz) using mutual information. Functional connectivity between neural-tracking signals was measured, and the Network-Based Statistics toolbox was used to: 1) assess the added value of the neural tracking vs EEG time series, 2) test between-group differences and 3) investigate any association with language performance in aphasia. Graph theory was also used to investigate topological alterations in aphasia.

Functional connectivity was higher when assessed from neural tracking compared to EEG time series. Persons with aphasia showed weaker low-gamma-band left-hemispheric connectivity, and graph theory-based results showed a greater network segregation and higher region-specific node strength. Aphasia also exhibited a correlation between delta-band connectivity within the left pre-frontal region and language performance.

We demonstrated the added value of neural tracking when investigating functional brain networks associated with natural speech processing in post-stroke aphasia. Its higher sensitivity to language-related brain circuits favours its use as informative biomarker for the assessment of aphasia.
Nitrous oxide respiration in acidophilic methanotrophs
Authors: Awala Samuel Imisi , Gwak Joo-Han , Kim Yongman , Jung Man-Young , Dunfield Peter. F. , Wagner Michael , Rhee Sung-Keun
Published: January 2024

Methanotrophic bacteria mitigate methane (CH4) emissions from natural environments. Although aerobic methanotrophs are considered strict aerobes, they are often highly abundant in extremely hypoxic and even anoxic environments. Despite the presence of denitrification genes, it remains to be verified whether denitrification contributes to their growth. Here, we revealed that two acidophilic methanotrophs encoding N2O reductase (clade I and type II nosZ, respectively):Methylocella tundraeT4 andMethylacidiphilum caldifontisIT6, respired N2O and grew anaerobically on diverse non-methane substrates, including methanol, C-C substrates, and hydrogen. However, NO3−and NO2−could be reduced during methanol oxidation inMethylocella tundraeT4 andMethylocella silvestrisBL2 without significantly increasing cell biomass. The lack of growth on methanol + NO3−or NO2−was likely due to the production of toxic reactive nitrogen species and C1 metabolites. However, the oxidation of pyruvate, a C3 electron donor, combined with NO3−or NO2−reduction resulted in anaerobic growth ofMethylocella tundraeT4 andMethylocella silvestrisBL2. In the extreme acidophile,Methylacidiphilum caldifontisIT6, N2O respiration supported cell growth at an extremely acidic pH of 2.0. InMethylocella tundraeT4, simultaneous consumption of N2O and CH4was observed in suboxic conditions, both in microrespirometry and growth experiments, indicating the robustness of its N2O reductase activity in the presence of O2. Furthermore, CH4oxidation per O2reduced in O2-limiting conditions increased when N2O was added, indicating that cells of T4 can direct more O2towards methane monooxygenase when respiring N2O as a terminal electron acceptor. Upregulation ofnosZand distinct repertories of methanol dehydrogenase-encoding genes (XoxF- and MxaFI-type) inMethylocella tundraeT4 cells grown anaerobically on methanol with N2O as the sole electron acceptor indicated adaptation mechanisms to anoxia. Our findings demonstrate that some methanotrophs can respire N2O independently or in tandem with O2, significantly expanding their potential ecological niche and paving the way for enhanced growth and survival in dynamic environments. This metabolic capability has application potential for simultaneously mitigating the emissions of the key greenhouse gases, CO2, CH4,and N2O, from natural and engineered environments.
Automating the Human Connectome Project’s Temporal ICA Pipeline
Authors: Yang Chunhui , Coalson Timothy S. , Smith Stephen M. , Elam Jennifer S. , Van Essen David C. , Glasser Matthew F.
Published: January 2024

Functional magnetic resonance imaging (fMRI) data are dominated by noise and artifacts, with only a small fraction of the variance relating to neural activity. Temporal independent component analysis (tICA) is a recently developed method that enables selective denoising of fMRI artifacts related to physiology such as respiration. However, an automated and easy to use pipeline for tICA has not previously been available; instead, two manual steps have been necessary: 1) setting the group spatial ICA dimensionality after MELODIC’s Incremental Group-PCA (MIGP) and 2) labeling tICA components as artifacts versus signals. Moreover, guidance has been lacking as to how many subjects and timepoints are needed to adequately re-estimate the temporal ICA decomposition and what alternatives are available for smaller groups or even individual subjects. Here, we introduce a nine-step fully automated tICA pipeline which removes global artifacts from fMRI dense timeseries after sICA+FIX cleaning and MSMAll alignment driven by functionally relevant areal features. Additionally, we have developed an automated “reclean” Pipeline for improved spatial ICA (sICA) artifact removal. Two major automated components of the pipeline are 1) an automatic group spatial ICA (sICA) dimensionality selection for MIGP data enabled by fitting multiple Wishart distributions; 2) a hierarchical classifier to distinguish group tICA signal components from artifactual components, equipped with a combination of handcrafted features from domain expert knowledge and latent features obtained via self-supervised learning on spatial maps. We demonstrate that the dimensionality estimated for the MIGP data from HCP Young Adult 3T and 7T datasets is comparable to previous manual tICA estimates, and that the group sICA decomposition is highly reproducible. We also show that the tICA classifier achieved over 0.98 Precision-Recall Area Under Curve (PR-AUC) and that the correctly classified components account for over 95% of the tICA-represented variance on multiple held-out evaluation datasets including the HCP-Young Adult, HCP-Aging and HCP-Development datasets under various settings. Our automated tICA pipeline is now available as part of the HCP pipelines, providing a powerful and user-friendly tool for the neuroimaging community.
Impact of Unc-51 Like Kinase 4 (ULK4) on the Reactivity of the Extended Reward System in Response to Conditioned Stimuli
Authors: Treutlein Jens , Löhlein Simone , Einenkel Karolin E. , Diekhof Esther K. , Gruber Oliver
Published: January 2024

Objectives

ULK4is an established candidate gene for mental disorders and antipsychotic treatment response and codes for a serine/threonine kinase that regulates the neural stem cell pool and controls cortex development. We investigated the effects of functional genetic variation at theULK4locus on the human extended dopaminergic reward system using functional magnetic resonance imaging (fMRI) during performance of a well-established reward paradigm.

Methods

234 study participants with functional neuroimaging (fMRI) data of the extended reward system and withULK4genotype data were included in this study. Effects of genetic variation in theULK4gene on reward system functioning were determined using the Desire-Reason-Dilemma (DRD) paradigm which allows to assess brain activation in response to conditioned reward stimuli (Diekhof et al. 2010).

Results

Among common missense variants of theULK4gene, variant prioritization revealed strongest functional signatures for variant rs17215589, coding for amino acid exchange Ala715Thr. For rs17215589 minor allele carriers, we detected increased activation responses to conditioned reward stimuli in the ventral tegmental area, the nucleus accumbens and several cortical brain regions of the extended reward system.

Conclusions

Our findings provide further evidence in humans that genetic variation inULK4may increase the vulnerability to mental disorders by modulating the function of the extended reward system. Future studies are needed to confirm the functional modulation of the extended reward system by ULK4 and to specify the role of this mechanism in the pathogenesis of psychiatric disorders.
Exploration of the EEG response to periodic thermal and vibrotactile stimuli
Authors: Courtin Arthur S. , Mouraux André
Published: January 2024

Under certain conditions, a stimulus applied at a given frequency will lead to a periodic variation of neural activity at the same frequency. Taking advantage of this periodicity, it is possible to tag this response in the EEG frequency spectrum. Frequency tagging of sustained periodic noxious heat stimuli led to the recording of phase-locked and non-phase-locked responses whose functional significance remains unclear.

This study aimed at assessing whether such responses can also be recorded during the repetitive presentation of brief innocuous cold, noxious heat and vibrotactile stimuli. Comparison between the responses obtained with different stimulation modalities should inform us on the nature of the neural processes underlying these responses (modality aspecific, somatosensory, thermosensory, nociceptive). Comparison between upper and lower limb stimulation should inform us on the somatotopic organization of these responses and, therefore, on their potential sources.

Based on our results, on one hand, trains of brief innocuous cold, noxious heat and vibrations can elicit phase-locked and non-phase-locked responses which appear highly similar to those evoked by sustained periodic noxious heat stimuli when frequency tagged. On the other hand, when analysed in the time domain or using time-frequency decomposition, these responses appeared highly similar to those that can be recorded following isolated brief noxious heat or tactile stimuli. These responses consisted in phase-locked activity corresponding to the vertex potential, thought to reflect modality non-specific attentional processes, and in an alpha-to-beta ERD originating in the S1/M1 area contralateral to the stimulated hand, probably reflecting non-specific somatosensory activity.
ARViS: A bleed-free multi-site automated injection robot for accurate, fast, and dense delivery of virus to mouse and marmoset brains
Authors: Nomura Shinosuke , Terada Shin-Ichiro , Ebina Teppei , Uemura Masato , Masamizu Yoshito , Ohki Kenichi , Matsuzaki Masanori
Published: January 2024

Genetically encoded fluorescent sensors continue to be developed and improved. If they could be expressed across multiple cortical areas in non-human primates, it would be possible to measure a variety of spatiotemporal dynamics of primate-specific cortical activity. Here, we develop an Automated Robotic Virus injection System (ARViS) for broad expression of a biosensor. ARViS consists of two technologies: image recognition of vasculature structures on the cortical surface to determine multiple injection sites without hitting them, and robotic control of micropipette insertion perpendicular to the cortical surface with 50-μm precision. In mouse cortex, ARViS sequentially injected virus solution into 100 sites over a duration of 100-minutes with a bleeding probability of only 0.1% per site. Furthermore, ARViS successfully achieved 266-site injections over the frontoparietal cortex of a common marmoset. We demonstrate one-photon and two-photon calcium imaging in the marmoset frontoparietal cortex, illustrating the effective expression of biosensors delivered by ARViS.
GABAB- GluK1 kainate receptor interplay modulates amygdala excitability and behavioral response to chronic stress
Authors: Ryazantseva Maria , Liiwand Maj , Lauri Sari E.
Published: January 2024

Amygdala hyperexcitability is a hallmark for stress-induced anxiety disorders. Stress-associated changes in both principal neurons and interneurons contribute to the increased excitability, but how exactly these mechanisms perturb function of behaviorally relevant circuits in the amygdala remains unclear. Here, we show that GluK1 subunit-containing kainate receptors in parvalbumin (PV) interneurons maintain high GABA release and control excitability of lateral amygdala (LA) principal neurons via tonic GABAB-receptor-mediated inhibition. Downregulation of GluK1 expression in PV interneurons after chronic restraint stress (CRS) releases the tonic inhibition and increases excitability of LA principal neurons. Stress-induced LA hyperexcitability facilitates glutamatergic transmission selectively to central amygdala PKCδ-expressing neurons, implicated in fear generalization. Consistent with significance in anxiogenesis, absence of GluK1- GABABregulation confers resilience against CRS-induced LA hyperexcitability and anxiety-like behavior. Our data reveal a unique novel mechanism involving an interplay between glutamatergic and GABAergic systems in the regulation of amygdala excitability in response to chronic stress.
Understanding functional brain reorganisation for naturalistic piano playing in novice pianists
Authors: Olszewska Alicja M. , Gaca Maciej , Droździel Dawid , Widlarz Agnieszka , Herman Aleksandra M. , Marchewka Artur
Published: January 2024

Learning to play the piano is a unique complex task, integrating multiple sensory modalities and higher-order cognitive functions. Longitudinal neuroimaging studies on adult novice musicians show training-related functional changes in music perception tasks. The reorganisation of brain activity while actually playing an instrument was studied only on a very short time-frame of a single fMRI session, and longer interventions have not yet been performed. Thus, our aim was to investigate the dynamic complexity of functional brain reorganisation while playing the piano within the first half year of musical training.

We scanned twenty-four novice keyboard learners (female, 18-23yo) using fMRI while they played increasingly complex musical pieces after 1, 6, 13 and 26 weeks of training.

Playing music evoked responses bilaterally in the auditory, inferior frontal and supplementary motor areas, and the left sensorimotor cortex. The effect of training over time, however, invoked widespread changes encompassing the right sensorimotor cortex, cerebellum, superior parietal cortex, anterior insula and hippocampus, among others. As the training progressed, the activation of these regions decreased while playing music. Post-hoc analysis revealed region-specific time-courses for independent auditory and motor regions of interest. These results suggest that while the primary sensory, motor and frontal regions are associated with playing music, the training decreases the involvement of higher-order cognitive control and integrative regions, and basal ganglia. Moreover, training might affect distinct brain regions in different ways, providing evidence in favour of the dynamic nature of brain plasticity.

Significance statement

Mastering the piano is a unique process requiring a collaboration of multiple brain regions. However, associated brain activation changes are not well understood. Using functional MRI, we showed that playing the piano activated brain areas associated with movement and auditory processing. However, as the novice pianists progressed through their training, the activation of other brain regions, involved in memory retrieval, auditory-motor integration, or the processing of musical syntax, was gradually reduced. Our findings suggest that musical training is an optimisation process, with higher-order cognitive networks being activated more strongly at the beginning and their activity decreasing with increased proficiency.
Do organisms need an impact factor? Citations of key biological resources including model organisms reveal usage patterns and impact
Authors: Piekniewska Agata , Anderson Nathan , Roelandse Martijn , Lloyd K. C. Kent , Korf Ian , Voss S. Randal , de Castro Giovanni , Magnani Diogo M. , Varga Zoltan , James-Zorn Christina , Horb Marko , Grethe Jeffery S. , Bandrowski Anita
Published: January 2024

Research resources like transgenic animals and antibodies are the workhorses of biomedicine, enabling investigators to relatively easily study specific disease conditions. As key biological resources, transgenic animals and antibodies are often validated, maintained, and distributed from university based stock centers. As these centers heavily rely largely on grant funding, it is critical that they are cited by investigators so that usage can be tracked. However, unlike systems for tracking the impact of papers, the conventions and systems for tracking key resource usage and impact lag behind. Previous studies have shown that about 50% of the resources are not findable, making the studies they are supporting irreproducible, but also makes tracking resources difficult. The RRID project is filling this gap by working with journals and resource providers to improve citation practices and to track the usage of these key resources. Here, we reviewed 10 years of citation practices for five university based stock centers, characterizing each reference into two broad categories: findable (authors could use the RRID, stock number, or full name) and not findable (authors could use a nickname or a common name that is not unique to the resource). The data revealed that when stock centers asked their communities to cite resources by RRID, in addition to helping stock centers more easily track resource usage by increasing the number of RRID papers, authors shifted from citing resources predominantly by nickname (∼50% of the time) to citing them by one of the findable categories (∼85%) in a matter of several years. In the case of one stock center, the MMRRC, the improvement in findability is also associated with improvements in the adherence to NIH rigor criteria, as determined by a significant increase in the Rigor and Transparency Index for studies using MMRRC mice. From this data, it was not possible to determine whether outreach to authors or changes to stock center websites drove better citation practices, but findability of research resources and rigor adherence was improved.
Selective manipulation of the host RNA-polymerase transcription fidelity increases phenotypic mutations in an insectParvovirus
Authors: Labadie Thomas , Cambray Guillaume
Published: January 2024

In the dynamic dance of evolution, organisms are often faced with fluctuating environments to which adaptation through selection of traditional heritable genetic mutations can be limiting. In this study, we unveil a refined mechanism of non-heritable variability in a virus with a compact DNA genome. We discovered that the genome of theJunona cœniadensovirus (JcDV) experiences a 10-fold lower transcription fidelity than the rest of the host’s transcriptome, despite the shared transcription machinery. We found that the virus’ capsid proteins interact with the host’s RNA Polymerase II, and further show that truncating these proteins through early stop codons largely restore the transcriptional fidelity of viral genes. These observations suggest a potential mechanism for the selective manipulation of transcription accuracy. We also pinpoint specific sequence contexts that may provide other knobs to finely control the local transcription fidelity. We estimate that this lower transcriptional fidelity results in more than 7% of the viral proteome bearing at least one non-synonymous mutation. The production of non-heritable functional diversity by hijacking the transcriptional machinery might be a refined strategy to enhance short term adaptation within the complex and ever-changing host-parasite interface, and might be shared by other genetic parasites. Our findings shed light on a virus-specific transcription fidelity control mechanism, expanding our understanding of adaptive strategies in biological entities.
Crosstalk interactions between transcription factors ERRα and PPARα assist PPARα-mediated gene expression
Authors: Desmet Sofie J. , Thommis Jonathan , Vanderhaeghen Tineke , Vandenboorn Edmee M. F. , Li Yunkun , Timmermans Steven , Fijalkowska Daria , Ratman Dariusz , Van Hamme Evelien , De Cauwer Lode , Staels Bart , Brunsveld Luc , Peelman Frank , Libert Claude , Tavernier Jan , De Bosscher Karolien
Published: January 2024

The peroxisome proliferator-activated receptor α (PPARα) is a crucial transcription factor governing genes associated with fatty acid β-oxidation. How various interacting proteins modulate PPARα’s transcriptional function remains incompletely understood. Employing an unbiased mammalian protein-protein interaction trap with liganded PPARα as bait, we identified an interaction with the orphan nuclear receptor estrogen-related receptor α (ERRα). Random mutagenesis scanning of PPARα’s ligand-binding domain and coregulator profiling experiments implicated bridging coregulators, whilein vitrostudies suggested a trimeric interaction involving RXRα. The PPARα·ERRα interaction, dependent on three C-terminal residues within ERRα’s helix 12, was reinforced by PGC1α and serum deprivation. Pharmacological inhibition of ERRα reduced its interaction with ligand-activated PPARα, revealing a transcriptome indicative of ERRα functioning as a transcriptional repressor on prototypical PPARα target genes. Intriguingly, ERRα exhibited opposite behavior on other PPARα targets, including the isolated PDK4 enhancer. Chromatin immunoprecipitation analyses demonstrated PPARα ligand-dependent recruitment of ERRα onto specific chromatin regions where PPARα binds in mouse livers. These findings highlight intricate transcriptional crosstalk mechanisms between PPARα and ERRα, suggesting a multi-layered regulatory network fine-tuning PPARα’s activity as a nutrient-sensing transcription factor.
Biomechanical properties of defence vibrations produced by bees
Authors: Vallejo-Marin Mario , Field David L. , Fornoni Juan , Montesinos Daniel , Dominguez Cesar A. , Hernandez Ivan , Vallejo Gillian C. , Woodrow Charlie , Barajas Ricardo Ayala , Jafferis Noah
Published: January 2024

Bees use thoracic vibrations produced by their indirect flight muscles for powering wingbeats in flight, but also during mating, pollination, defence, and nest building. Previous work on non-flight vibrations has mostly focused on acoustic (airborne vibrations) and spectral properties (frequency domain). However, mechanical properties such as the vibration’s acceleration amplitude are important in some behaviours, e.g., during buzz pollination, where higher amplitude vibrations remove more pollen from flowers. Bee vibrations have been studied in only a handful of species and we know very little about how they vary among species. Here, we conduct the largest survey to date of the biomechanical properties of non-flight bee buzzes. We focus on defence buzzes as they can be induced experimentally and provide a common currency to compare among taxa. We analysed 15,000 buzzes produced by 306 individuals in 65 species and six families from Mexico, Scotland, and Australia. We found a strong association between body size and the acceleration amplitude of bee buzzes. Comparison of genera that buzz-pollinate and those that do not suggests that buzz-pollinating bees produce vibrations with higher acceleration amplitude. We found no relationship between bee size and the fundamental frequency of defence buzzes. Although our results suggest that body size is a major determinant of the amplitude of non-flight vibrations, we also observed considerable variation in vibration properties among bees of equivalent size and even within individuals. Both morphology and behaviour thus affect the biomechanical properties of non-flight buzzes.

Summary statement

Analyses across 65 bee taxa in three continents indicates that body size is a major determinant of the acceleration amplitude but not the oscillation frequency of non-flight thoracic vibrations.
Simultaneous, cortex-wide and cellular-resolution neuronal population dynamics reveal an unbounded scaling of dimensionality with neuron number
Authors: Manley Jason , Demas Jeffrey , Kim Hyewon , Martínez Traub Francisca , Vaziri Alipasha
Published: January 2024

The brain’s remarkable properties arise from collective activity of millions of neurons. Widespread application of dimensionality reduction to multi-neuron recordings implies that neural dynamics can be approximated by low-dimensional “latent” signals reflecting neural computations. However, what would be the biological utility of such a redundant and metabolically costly encoding scheme and what is the appropriate resolution and scale of neural recording to understand brain function? Imaging the activity of one million neurons at cellular resolution and near-simultaneously across mouse cortex, we demonstrate an unbounded scaling of dimensionality with neuron number. While half of the neural variance lies within sixteen behavior-related dimensions, we find this unbounded scaling of dimensionality to correspond to an ever-increasing number of internal variables without immediate behavioral correlates. The activity patterns underlying these higher dimensions are fine-grained and cortex-wide, highlighting that large-scale recording is required to uncover the full neural substrates of internal and potentially cognitive processes.