bluuebunny/crossref_metadata_2025 huggingface dataset:
Bilateral field advantage of spatial attention in macaque lateral prefrontal cortex
Authors: Kadijani Maryam Nouri , Backen Theda , Machanda Kaustubh , Mody Sandeep K , Treue Stefan , Martinez-Trujillo Julio C.
Published: May 2024

Allocating visual attention to behaviorally relevant stimuli is easier when distractors are located in the opposite visual hemifield relative to when they are in the same hemifield. The neural mechanisms underlying this bilateral field advantage remains unclear. We documented this effect in two macaques performing a covert spatial attention task in two different conditions: when the target and distracter were positioned in different hemifields (across condition), and when they were positioned on the top and bottom quadrants within the same visual hemifield (within condition). The animals’ behavioral performance at detecting a change in the attended stimulus was higher in the across relative to the within condition. We recorded the responses of lateral prefrontal cortex (LPFC, area 8A) neurons in one animal. The proportion of LPFC neurons encoding the allocation of attention was larger in the across relative to the within condition. The latter was accompanied by an increase in the ability of single neurons to discriminate the allocation of attention in the across relative to the within condition. Finally, we used linear classifiers to decode the allocation of attention from the activity of neuronal ensembles and found a similar bilateral field advantage in decoding performance in the across relative to the within condition. Our finding provides a neural correlate of the bilateral field advantage reported in behavioral studies of attention and suggest that the effect may originate within the LPFC circuitry.
The mechanisms and neural signature of average numerosity perception
Authors: Togoli Irene , Collignon Olivier , Bueti Domenica , Fornaciai Michele
Published: May 2024

The human brain is endowed with an intuitive sense of number allowing to perceive the approximate quantity of items in a scene, or “numerosity.” This ability is not limited to items distributed in space, but also to events unfolding in time and to theaveragenumerosity of dynamic scenes. How the brain computes and represents the average numerosity over time however remains mostly unclear. Here we investigate the mechanisms and electrophysiological (EEG) signature of average numerosity perception. To do so, we used dynamic stimuli composed of 3-12 arrays presented for 50 ms each, and asked participants to judge the average numerosity of the sequence. Our results first show that the weight of different arrays in the sequence in determining the judgement is subject to both primacy and recency effects, depending on the length of the sequence. Moreover, we show systematic perceptual adaptation effects across trials, with the bias on numerical estimates depending on both the average numerosity and length of the preceding stimulus. The EEG results show numerosity-sensitive brain responses starting very early after stimulus onset, and that activity around the offset of the sequence can predict both the accuracy and precision of judgments. Additionally, we show a neural signature of the adaptation effect at around 300 ms, whereby the amplitude of brain responses can predict the strength of the bias. Overall, our findings support the existence of a dedicated, low-level perceptual mechanism involved with the computation of average numerosity, and highlight the processing stages involved with such process.
Magnitude processing and integration entail perceptual processes independent from the task
Authors: Togoli Irene , Collignon Olivier , Bueti Domenica , Fornaciai Michele
Published: May 2024

The magnitude dimensions of visual stimuli, such as their numerosity, duration, and size, are intrinsically linked, leading to mutual interactions across them. However, it remains debated whether such interaction across dimensions, or “magnitude integration” effects, arise from low-level perceptual processes that are independent from the task performed, or whether they instead arise from high-level decision-making processes. We address this question with two experiments in which participants watched a series of dot-array stimuli modulated in numerosity, duration, and item size. In experiment 1 (task condition), the task required participants to either judge the numerosity, duration, or size of each stimulus. In experiment 2 (passive condition), instead, a separate group of participants passively watched the stimuli. The behavioral results obtained in the task show robust magnitude integration effects across all three dimensions. Then, we identify a neural signature of magnitude integration by showing that event-related potentials at several latency windows (starting at ∼100-200 ms after stimulus onset) can predict the effect measured behaviorally. In the passive condition, we demonstrate an almost identical modulation of brain responses, occurring at the same processing stages as during the task. Importantly, using a cross-condition multivariate decoding analysis, we demonstrate that brain responses to magnitude in the task condition can predict the response in the passive condition at specific latency windows. These results thus suggest that magnitude processing and integration likely occurs via automatic perceptual processes that are engaged irrespective of the task-relevance of the stimuli, and independently from decision making.
Goldfinder: Unraveling Networks of Gene Co-occurrence and Avoidance in Bacterial Pangenomes
Authors: Gavriilidou Athina , Paulitz Emilian , Resl Christian , Ziemert Nadine , Kupczok Anne , Baumdicker Franz
Published: May 2024

The pangenome is the set of all genes present in a prokaryotic species. Most pangenomes contain many accessory genes that are present in only some of the species members. Genes need to function together, and it has been suggested that selection for certain gene combinations affects the structure of prokaryotic pangenomes. Nevertheless, genes might also co-occur simply due to being linked on the genome, and efficient tools are needed to distinguish linkage from co-selection. Here we present Goldfinder, an approach to infer co-occurrence and co-avoidance between gene pairs by taking the phylogenetic relationships of the species into account. The approach is implemented in an efficient Python script available athttps://github.com/fbaumdicker/goldfinder. We also provide scripts for clustering co-occurring genes and for visualizing the resulting co-occurrence and co-avoidance networks in Cytoscape. In comparison to the co-occurrence inference tool Coinfinder, Goldfinder finds fewer co-occurring pairs in a real species pangenome, suggesting that fewer spurious associations due to phylogenetic dependencies are detected. We conclude that Goldfinder is a fast and accurate tool to infer gene co-occurrence and co-avoidance, which will enable large-scale analyses to infer co-selected genes across bacterial pangenomes.
Augment Single-cell RNA-seq data with Surface Protein Levels using Gene set-based Deep Learning and Transfer Learning Methods
Authors: Hasib Md Musaddaqul , Zhang Tinghe , Zhang Jianqiu , Gao Shou-jiang , Huang Yufei
Published: May 2024

As scRNA-seq becomes increasingly accessible, providing a cost-efficient method to augment surface protein levels from gene expression measurements are desirable. We proposed a machine learning approach that includes a novel geneset neural network (GS-NN) that aims to learn robust and biologically meaningful features and a highly efficient transfer learning strategy to address cross-dataset differences. We conducted comprehensive experiments to show the improvements of the proposed methods. Specifically, we demonstrate that GS-NN learns more robust features to achieve better cross-subject performance than other machine learning approaches. Transfer learning further improves that of GS-NN by reducing dataset differences through highly efficient fine-tuning. The unique genesets design of GS-NN also allows identification of functions contributing to the prediction and improvement of the proposed strategy. Overall, this study reports a novel approach to robustly augment.

Key Points

The article presents a machine learning approach, Geneset Neural Network(GS-NN) to augment surface protein levels from single-cell RNA sequencing(scRNA-seq) gene expression data.

The GS-NN aims to learn robust and biologically meaningful features, and the approach includes a highly efficient transfer learning strategy to address cross-dataset differences in scRNA-seq data.

Comprehensive experiments demonstrate that GS-NN learns more robust features using trasfer learning techniques achieving better cross-subject performance compared to other machine learning approaches.

The unique geneset-based architecture of GS-NN allows the identification and interpretion of biological functions contributing to the prediction of cell surface protein level.

GS-NN’s architecture is conveniently transferrable across datasets, making it valuable tool for researchers working with diverse scRNA-seq datasets.
Physiological Processing of Aversiveness in the Mind’s Ear: Comparing Audiovisual, Auditory and Imagined Auditory Affective Stimuli
Authors: Yang Xuan , Oh Sewon , Stanley Jacob , Hammons Sarah , Anderson Ashley , Wedell Douglas H. , Shinkareva Svetlana V.
Published: May 2024

Understanding the somatovisceral responses to auditory affective imagery has important implications in disorders like misophonia. The current study compared physiological responses to aversive and nonaversive states across three modalities: audiovisual, auditory, and auditory imagery. Electromyographic activity over corrugator supercilii (EMGc) and zygomaticus major (EMGz), electrodermal activity (EDA), heart rate (HR), and finger skin temperature (SKT) were measured. There was significant differentiation in EMGc, EDA, and HR deceleration between aversive and nonaversive audiovisual stimuli. EMGc potentiation was the only physiological measure showing consistent differentiation across the three modalities. Cross-modal aversiveness classification results revealed a similar physiological response pattern between audiovisual and auditory modalities. The physiological response pattern during auditory affective imagery was useful for predicting the aversiveness in audiovisual modality but not the other way around. Vividness in auditory imagery correlated with subjective hedonic valence ratings, but not physiological responses. Taken together, the current data suggest that the aversiveness of auditory imagery is differentiable in subjective affective experience and facial muscle potentiation. These results of the physiological responses to imagined aversive sounds in nonclinical population would serve as a comparison baseline for the study of misophonia.
Sodium-glucose co-transporter 2 Inhibitors Act Independently ofSGLT2to Confer Benefit for Heart Failure with Reduced Ejection Fraction in Mice
Authors: Berger Justin H. , Matsuura Timothy R. , Bowman Caitlyn E. , Taing Renee , Patel Jiten , Lai Ling , Leone Teresa C. , Reagan Jeffrey D. , Haldar Saptarsi M. , Arany Zoltan , Kelly Daniel P.
Published: May 2024

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are novel, potent heart failure medications with an unknown mechanism of action. We sought to determine if the beneficial actions of SGLT2i in heart failure were on- or off-target, and related to metabolic reprogramming, including increased lipolysis and ketogenesis. The phenotype of mice treated with empagliflozin and genetically engineered mice constitutively lacking SGLT2 mirrored metabolic changes seen in human clinical trials (including reduced blood glucose, increased ketogenesis, and profound glucosuria). In a mouse heart failure model, SGLT2i treatment, but not generalized SGLT2 knockout, resulted in improved systolic function and reduced pathologic cardiac remodeling. SGLT2i treatment of the SGLT2 knockout mice sustained the cardiac benefits, demonstrating an off-target role for these drugs. This benefit is independent of metabolic changes, including ketosis. The mechanism of action and target of SGLT2i in HF remain elusive.
AutoTA: Galaxy Workflows for Reproducible and Automated Taxonomic Analysis using Qiime2
Authors: Tikhe Atharva , Jangam Shweta , Arora Preeti , Gupte Sanjay , Shah Sarjan
Published: May 2024

Metagenomic sequencing allows systematic characterization of microbial populations isolated from various environments of interest by bypassing the culturing of the isolates. Concomitant to advancement in sequencing techniques, analysis methods and softwares have also grown to be sophisticated and efficient. Qiime2 is a collection of python scripts which enables end-to-end analysis of metagenomic data. However, usage of latest and more complex databases for classification is hindered by requirement of high compute power. To aid cloud-based analysis, we present workflows for diversity analysis and taxonomic assignment which are the two most common and initial steps in a metagenomics experiments. The workflows are made in Galaxy which makes testing and analysing multiple datasets faster, in parallel, reproducible and flexible. The workflows can be integrated into a local Galaxy instance or used completely on the web which is of great importance to non-bioinformaticians and bench scientists.
Decoding the Language of Chickens - An Innovative NLP Approach to Enhance Poultry Welfare
Authors: Neethirajan Suresh
Published: May 2024

This research investigates the utilization of the Natural Language Processing-based WHISPER model for decoding chicken vocalizations, with the goal of comprehending the semantics and emotions embedded in their vocal communications. By leveraging advanced acoustic analysis techniques, the study focuses on interpreting the syntax and temporal patterns inherent in the vocalizations to discern the underlying affective states of chickens. This approach facilitates a non-invasive method of monitoring poultry welfare, enhancing traditional animal welfare assessments which often rely on direct human observation and can induce stress in the animals. The principal results from the application of the WHISPER model demonstrate its efficacy in classifying various chicken vocalizations into distinct categories that reflect specific emotional states such as distress, contentment, and fear. This classification is achieved by analyzing the frequency, duration, and intensity of vocalizations, thus providing a detailed insight into the emotional well-being of the animals. Our findings indicate that real-time monitoring of chicken vocalizations using NLP techniques can significantly improve the responsiveness and precision of welfare interventions. This method reduces the need for human interaction, minimizes stress for the animals, and allows for the continuous assessment of their well-being in a farming environment. Furthermore, the research highlights the potential of NLP tools in recognizing and interpreting complex animal vocalizations, which could lead to advancements in automated animal welfare monitoring systems. This study underscores the transformative potential of integrating sophisticated computational models like the WHISPER NLP model into animal welfare practices. By providing a more humane and efficient approach to monitoring animal welfare, this research contributes to the broader field of precision livestock farming, suggesting a shift towards more scientifically informed and welfare-centric farming practices. The application of such technologies not only aids in the immediate improvement of animal welfare but also supports sustainable farming operations by promoting the health and productivity of poultry through enhanced welfare standards.
The chromatin remodeler CHD3 is highly expressed in mature neurons and regulates genes involved in synaptic development and function
Authors: den Hoed Joery , Wong Maggie M. K. , Claassen Willemijn J. J. , de Hoyos Lucía , Lütje Lukas , Heide Michael , Huttner Wieland B. , Fisher Simon E.
Published: May 2024

Changes in the dynamics of chromatin state that control spatiotemporal gene expression patterns are crucial during brain development. CHD3 is a chromatin remodeler that is highly expressed during neurogenesis and that functions as a core member of the NuRD complex, a large multiprotein complex mediating chromatin state. Genetic disruptions inCHD3have been implicated in a neurodevelopmental disorder characterized by intellectual disability, macrocephaly and severe speech deficits. To study the roles of CHD3 during early human brain development, we generated induced pluripotent stem cells with heterozygous and homozygous loss-of-function mutations, differentiated them into unguided neural organoids and cortical neurons, and analyzed these by immunohistochemistry, bulk RNA-, single-cell RNA-, and ChIP-sequencing. Loss ofCHD3expression had no detectable effects on early neuroepithelium formation and organoid growth, nor did it significantly affect cell type composition or neuronal differentiation speed. Instead, upon loss ofCHD3, we observed dysregulation of genes related to axon guidance and synapse development across all datasets, identifying a novel role for the protein as a regulator that facilitates neurogenesis, in particular neuronal maturation. Our results based on genetically engineered knockout organoids pave the way for future studies modeling the neurobiological pathways affected in CHD3-related disorder.
Atomic resolution map of the solvent interactions driving SOD1 unfolding in CAPRIN1 condensates
Authors: Ahmed Rashik , Liang Mingyang , Hudson Rhea P. , Rangadurai Atul K. , Huang Shuya Kate , Forman-Kay Julie D. , Kay Lewis E.
Published: May 2024

Biomolecules can be sequestered into membrane-less compartments, referred to as biomolecular condensates. Experimental and computational methods have helped define the physical-chemical properties of condensates. Less is known about how the high macromolecule concentrations in condensed phases contribute “solvent” interactions that can remodel the free-energy landscape of other condensate-resident proteins, altering thermally accessible conformations and, in turn, modulating function. Here, we use solution Nuclear Magnetic Resonance (NMR) spectroscopy to obtain atomic resolution insights into the interactions between the immature form of superoxide dismutase 1 (SOD1), which can mislocalize and aggregate in stress granules, and the RNA-binding protein CAPRIN1, a component of stress granules. NMR studies of CAPRIN1:SOD1, focused on both unfolded and folded SOD1 states in mixed phase and de-mixed CAPRIN1-based condensates, establish that CAPRIN1 shifts the folding equilibrium of SOD1 towards the unfolded state through preferential interactions with the unfolded ensemble, with little change to the structure of the folded conformation. Key contacts between CAPRIN1 and the H80-H120 region of unfolded SOD1 are identified, as well as SOD1 interaction sites near both the arginine-rich and aromatic-rich regions of CAPRIN1. Unfolding of immature SOD1 in the CAPRIN1 condensed phase is shown to be coupled to aggregation, while a more stable zinc-bound, dimeric form of SOD1 is less susceptible to unfolding when solvated by CAPRIN1. Our work underscores the impact of the condensate solvent environment on the conformational states of resident proteins and supports the hypothesis that ALS mutations that decrease metal binding or dimerization function as drivers of aggregation in condensates.

Significance Statement

Biomolecular condensates concentrate proteins and nucleic acids to regulate and perform key biological functions. Although the material properties of these condensates are well-studied, much less is understood about how the structure and dynamics of proteins within them are affected by the high concentration of biomolecules. In this study we have used NMR spectroscopy to study how the folding equilibrium and structural dynamics of the ALS protein SOD1 are modulated inside a condensate formed by CAPRIN1. Our study reveals that the CAPRIN1 condensed phase biases an immature form of SOD1 towards unfolded states that are susceptible to aggregation and provides insights into why this is the case, while a more mature form of the protein is much less affected.
A central role for Numb/Nbl in multiple Shh-mediated axon repulsion processes
Authors: Dolique Tiphaine , Baudet Sarah , Charron Frederic , Ferent Julien
Published: May 2024

Sonic hedgehog (Shh) is an axon guidance molecule that can act as either a chemorepellent or a chemoattractant, depending on the neuron type and their developmental stage. In the developing spinal cord, Shh initially attracts commissural axons to the floor plate and later induces their repulsion after they cross the midline. In the developing visual system, Shh repels ipsilateral retinal ganglion cell (iRGC) axons at the optic chiasm. Although Shh requires the endocytic adaptor Numb for attraction of commissural neurons, the molecular mechanisms underlying Shh dual function in attraction and repulsion are still unclear. In this study, we investigate whether Numb also regulates repulsive axon guidance. We show that Numb is essential for two Shh-mediated repulsion processes: iRGC axon repulsion at the optic chiasm and antero-posterior commissural axon repulsion in the spinal cord. Therefore, Numb is required for Shh-mediated attraction and repulsion. These results position Numb as a central player in the non-canonical Shh signalling pathway mediating axon repulsion.

Summary statement

Here, we show that Numb is required for Shh-mediated midline repulsion of ipsilateral retinal ganglion cell axons and post-crossing commissural axons of the spinal cord.
Divergent short-term plasticity creates parallel pathways for computation and behavior in an olfactory circuit
Authors: Kim Hyong S. , Jeanne James M.
Published: May 2024

To enable diverse sensory processing and behavior, central circuits use divergent connectivity to create parallel pathways. However, linking subcellular mechanisms to the circuit-level segregation of computation has been challenging. Here, we investigate the generation of parallel processing within a divergent network in theDrosophilaolfactory system, where single projection neurons target multiple types of lateral horn neuron (LHN). One LHN type generates sustained responses and adapts divisively to encode temporal odor contrast. The other generates transient responses and adapts subtractively to encode a form of positive temporal prediction error. These coding differences originate from subcellular differences in short-term plasticity in projection neuron axons. Prediction error arises from strongly facilitating synapses, which depend on the presynaptic priming factor Unc13B. The temporal contrast code arises from mildly depressing synapses that engage additional gain control implemented by the Na+/K+ATPase in the postsynaptic neuron. Each LHN type makes corresponding dynamic contributions to behavioral odor attraction. Subcellular synaptic specialization is a compact and efficient way to generate diverse parallel information streams.
Adolescent and adult mice use both incremental reinforcement learning and short term memory when learning concurrent stimulus-action associations
Authors: Chase Juliana B. , Xia Liyu , Tai Lung-Hao , Lin Wan Chen , Collins Anne G.E. , Wilbrecht Linda
Published: May 2024

Computational modeling has revealed that human research participants use both rapid working memory (WM) and incremental reinforcement learning (RL) (RL+WM) to solve a simple instrumental learning task, relying on WM when the number of stimuli is small and supplementing with RL when the number of stimuli exceeds WM capacity. Inspired by this work, we examined which learning systems and strategies are used by adolescent and adult mice when they first acquire a conditional associative learning task. In a version of the human RL+WM task translated for rodents, mice were required to associate odor stimuli (from a set of 2 or 4 odors) with a left or right port to receive reward. Using logistic regression and computational models to analyze the first 200 trials per odor, we determined that mice used both incremental RL and stimulus-insensitive, one-back strategies to solve the task. While these one-back strategies may be a simple form of short-term or working memory, they did not approximate the boost to learning performance that has been observed in human participants using WM in a comparable task. Adolescent and adult mice also showed comparable performance, with no change in learning rate or softmax beta parameters with adolescent development and task experience. However, reliance on a one-back perseverative, win-stay strategy increased with development in males in both odor set sizes. Our findings advance a simple conditional associative learning task and new models to enable the isolation and quantification of reinforcement learning alongside other strategies mice use while learning to associate stimuli with rewards within a single behavioral session. These data and methods can inform and aid comparative study of reinforcement learning across species.

Author summary

Here we studied the strategies and mechanisms mice use to learn a simple two choice odor based task in a single session. Using a set size manipulation and computational models we find evidence that mice use incremental reinforcement learning as well as several short-term (one-back) strategies to earn water reward. Our data and models clarify how mice learn a simple task and establish methods by which mouse and human reinforcement learning may be isolated for cross-species comparison of learning.
Clinical epidemiology of the endoscopic, laparoscopic, and surgical resection of malignant gastric tumors in Japan, 2014-2021: a retrospective study using open data from a national claims database
Authors: Sako Akahito , Yada Tomoyuki , Fujiya Keiichi , Nakashima Ryo , Yoshimura Kensuke , Yanai Hidekatsu , Uemura Naomi
Published: May 2024

Background

Gastric cancer is one of the most common malignancies and its incidence is high in East Asia. Several options are available for resection of malignant gastric tumors, ranging from endoscopic resection of early-stage cancer to open total gastrectomy. However, there has been a lack of nationwide data on gastric resection in Japan.

Methods

This observational study analyzed data from the publicly accessible National Database of Health Insurance Claims and Specific Health Checkups, which includes most national health insurance claims data in Japan. Trends in the various types of resection performed for malignant gastric tumors between 2014 and 2021, the age and sex distributions of patients undergoing these procedures, and regional disparities were investigated.

Results

The annual number of resections was highest in 2015 (109,000) and lowest in 2020 (90,000) after the COVID-19 pandemic. The proportion of endoscopic resections increased from 47% in 2014 to 57% in 2021 while the proportion of total gastrectomies performed during this period decreased from 17% to 10%. In 2021, 70% of patients who underwent resection were men. That year, 83.8% of all patients who underwent any type of gastric resection and 87.1% of those who underwent endoscopic submucosal dissection (ESD) were aged ≥65 years. The annual incidence of gastric resection per million general population was highest in Tottori (n=1,236) and lowest in Okinawa (n=251). The proportion of endoscopic resections was highest in Miyagi (66%) and lowest in Aichi (45%) and that of open surgery was highest in Aomori (36%) and lowest in Wakayama (5%).

Conclusions

Gastric malignancy is increasingly treated by endoscopic submucosal dissection rather than by open total gastrectomy. However, there are regional disparities in the resection methods used. Standardization of screening and treatment and a more even distribution of specialists are needed.
Long-COVID improves in 50% of patients after a year in a Midwestern cohort
Authors: Stalker Grant , Tudas Rosarie , Garg Alpana , Graham Lauren , Thurman Andrew L. , Wiblin R. Todd , Hamzeh Nabeel , Blount Robert J. , Villacreses Raul , Zabner Joseph , Comellas Alejandro , Cho Josalyn L. , Pezzulo Alejandro
Published: May 2024

Background

Many of those infected with COVID-19 experience long-term disability due to persistent symptoms known as Long-COVID, which include ongoing respiratory issues, loss of taste and smell, and impaired daily functioning.

Research Question

This study aims to better understand the chronology of long-COVID symptoms.

Study Design and Methods

We prospectively enrolled 403 adults from the University of Iowa long-COVID clinic (June 2020 to February 2022). Participants provided symptom data during acute illness, symptom progression, and other clinical characteristics. Patients in this registry received a survey containing questions including current symptoms and status since long-COVID diagnosis (sliding status scale, PHQ2, GAD2, MMRC). Those >12 months since acute-COVID diagnosis had chart review done to track their symptomology.

Results

Of 403 participants contacted, 129 (32%) responded. The mean age (in years) was 50.17 +/−14.28, with 31.8% male and 68.2% female. Severity of acute covid treatment was stratified by treatment in the outpatient (70.5%), inpatient (16.3%), or ICU (13.2%) settings. 51.2% reported subjective improvement (sliding scale scores of 67-100) since long-COVID onset. Ages 18-29 reported significantly higher subjective status scores. Subjective status scores were unaffected by severity. 102 respondents were >12 months from their initial COVID-19 diagnosis and were tracked for longitudinal symptom persistence. All symptoms tracked had variance (mean fraction 0.58, range 0.34-0.75) in the reported symptoms at the time of long-COVID presentation when compared with patient survey report. 48 reported persistent dyspnea, 23 (48%) had resolved it at time of survey. For fatigue, 44 had persistence, 12 (27%) resolved.

Interpretation

Overall, 51.2% respondents improved since their long-COVID began. Pulmonary symptoms were more persistent than neuromuscular symptoms (anosmia, dysgeusia, myalgias). Gender, time since acute COVID infection, and its severity didn’t affect subjective status or symptoms. This study highlights recall bias that may be prevalent in other long-COVID research reliant on participant memory.
Altered Brain Glucose Metabolism in COVID-19 disease: An activation likelihood estimation Meta-analysis
Authors: Kang Dongju , Jung Hyunji , Pak Kyoungjune
Published: May 2024

Purpose

COVID-19, caused by the SARS-CoV-2 virus, has significantly altered modern society and lifestyles. We investigated its impact on brain glucose metabolism by meta-analyzing existing studies that utilized 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scans of the brain.

Methods

We conducted a systematic search of MEDLINE and EMBASE databases from inception to August 2023 for English-language publications using the keywords “positron emission tomography,” “single-photon emission computed tomography,” and “COVID-19.” We included original research articles that reported changes in brain glucose metabolism following COVID-19 infection. ALE values from these studies were aggregated and tested against a null hypothesis that anticipated a random distribution of ALE values, which proved to be significantly higher than chance.

Results

We identified eight papers that met our inclusion criteria. Significant increases in brain glucose metabolism were noted in the left anterior cingulate gyrus, right thalamus, and brainstem. In children with COVID-19, decreased glucose metabolism was observed in the right and left cerebellum, left amygdala/hippocampus, left anterior cingulate gyrus, and right amygdala. In adults with COVID-19, decreased metabolism was seen in the right temporal lobe, brainstem (acute phase), left posterior cingulate gyrus, left precuneus, right cerebellum, right insula, right anterior cingulate gyrus, left occipital lobe, and left globus pallidus (chronic phase).

Conclusion

COVID-19 impacts brain glucose metabolism, typically manifesting as areas of decreased metabolism in18F-FDG PET scans, though increases are also observed. These changes in metabolism vary with the patient’s age and the time elapsed between the diagnosis of COVID-19 and the PET scan.
Envelope-dimer epitope-like broadly protective antibodies against dengue in children following natural infection and vaccination
Authors: Mpingabo Patrick I. , Ylade Michelle , Aogo Rosemary A. , Crisostomo Maria Vinna , Thiono Devina J. , Daag Jedas Veronica , Agrupis Kristal-An , Escoto Ana Coello , Raimundi-Rodriguez Guillermo L. , Odio Camila D. , Fernandez Maria Abad , White Laura , de Silva Aravinda M. , Deen Jacqueline , Katzelnick Leah C.
Published: May 2024

Cross-reactive antibodies (Abs) to epitopes that span envelope proteins on the virion surface are hypothesized to protect against dengue. Here, we measured Abs targeting the quaternary envelope dimer epitope (EDE) as well as neutralizing and binding Abs and evaluate their association with dengue virus (DENV) infection, vaccine response, and disease outcome in dengue vaccinated and unvaccinated children (n=252) within a longitudinal cohort in Cebu, Philippines (n=2,996). Abs targeting EDE were prevalent and strongly associated with broad neutralization of DENV1-4 in those with baseline multitypic immunity. Subsequent natural infection and vaccination boosted EDE-like, neutralizing, and binding Abs. EDE-like Abs were associated with reduced dengue risk and mediated the protective effect of binding and neutralizing Abs on symptomatic and severe dengue. Thus, Abs targeting quaternary epitopes help explain broad cross protection in those with multiple prior DENV exposures, making them useful for evaluation and development of future vaccines and therapeutics.
Moving out and moving on: the impact of mobility in a context of union dissolution on antidepressants intake in Belgium
Authors: Damiens Joan , Schnor Christine , Willaert Didier
Published: May 2024

This research investigates the role of residential mobility in the relation between union dissolution and antidepressants intake. The dataset gathers information on 20 to 64-year-old individuals affiliated with the Belgian socialist health insurance fund – the largest public health insurance fund in French-speaking Belgium – and who lived in marital or non-marital opposite-sex partnerships in 2008 and separated between 2009 to 2018 (N=68,048). We used antidepressant consumption (>= 90 defined daily doses per year) as a dependent variable and conducted random-effect logistic regression models. Controlling for observed and unobserved individuals’ characteristics, we found that, mobility – defined by a change of municipality – during the year and/or the year following the separation is not associated with higher or lower antidepressants intake than staying on the previously shared place after the separation. However, we observe anticipatory effects for women: women who moved during their separation year had a higher medication use than women who stayed in the previously shared municipality. Repartnership is associated with lower antidepressants consumption for women, especially if they leave the shared place.
Gut microbiome co-abundance networks varies with age, sex, smoking status and body mass index
Authors: Boetto Christophe , Basten Romero Violeta , Henches Leo , Frouin Arthur , Auvergne Antoine , Patin Etienne , Bredon Marius ,   Milieu Interieur Consortium, Kennedy Sean , Duffy Darragh , Quintana-Murci Lluis , Sokol Harry , Aschard Hugues
Published: May 2024

The gut microbiome is a complex ecosystem whose members develop local interactions to form coherent functional communities. Variability in these communities, typically investigated through taxa co-abundance, might provide critical insights on the biological links between the gut microbiome and human phenotypes. However, existing methods to investigate variations in taxa co-abundance suffer multiple limitations. Here, we address the simple but challenging question of identifying factors associated with variability in gut microbiome taxa co-abundance using a novel covariance-based method that resolve these limitations. We screened 80 host factors in 938 healthy participants, and identified associations between taxa co-abundance variability and age, sex, smoking status, and body mass index (BMI) not captured by abundance-based and diversity-based methods. Increased age and smoking were associated with an overall decrease in co-abundance, and conversely BMI with an increase. Finally, we demonstrate that the proposed approach offers a powerful framework for describing taxa networks at the individual level and predicting host features.
An ultrasound-guided biopsy technique for obtaining supraclavicular brown fat biopsies and preadipocytes
Authors: Andersen Eline S. , Jespersen Naja Zenius , Henriksen Tora Ida , Pedersen Bente Klarlund , Scheele Camilla , Nielsen Michael Bachmann , Nielsen Søren
Published: May 2024

Studying activated human brown adipose tissue (BAT) in vivo poses challenges due to its intricate anatomical positioning. Through the implementation of an ultrasound-guided biopsy technique, we successfully collected BAT samples from the supraclavicular region of 27 healthy individuals. As a comparative control, subcutaneous white adipose tissue (WAT) was similarly extracted from the same participants. Furthermore, we isolated progenitor cells from four tissue biopsies in both regions, subsequently subjecting them to a 12-day in vitro differentiation protocol following stimulation with 10 µM norepinephrine. To assess the mRNA expression of thermogenic genes within these small tissue samples, we employed a targeted cDNA amplification procedure, followed by conventional quantitative PCR (qPCR). Our study demonstrated that, with further refinement, this biopsy methodology can be used to obtain thermogenic adipose tissue. However, the expression data exhibited considerable diversity, and no statistically significant overall trends emerged for any of the five BAT marker genes (UCP1, PPARGC1A, PRDM16, CIDEA, CITED1), nor for the WAT marker HOXC8. The differentiation capacity of the progenitor cells revealed irregularities, with only three adipocyte cultures (two WAT and one BAT) displaying satisfactory differentiation potential. Remarkably, the differentiated BAT culture displayed a significantly elevated basal UCP mRNA expression level, further induced by 1.7-fold upon stimulation with norepinephrine. In summary, based on the in vitro data, brown adipose samples can be obtained using our ultrasound-guided biopsy technique approach. However, significant refinements are necessary before robust in vivo data can be generated in future intervention studies.
Arachidonic acid incorporation into phosphatidylinositol by LPLAT11/MBOAT7 ensures radial glial cell integrity in developing neocortex
Authors: Ishino Yuki , Kishi Yusuke , Iwama Taiga , Kuwayama Naohiro , Arai Hiroyuki , Gotoh Yukiko , Aoki Junken , Kono Nozomu
Published: May 2024

Arachidonic acid, a vital polyunsaturated fatty acid in brain development, is enriched in phosphatidylinositol (PI). The arachidonic acyl chain in PI is introduced by lysophospholipid acyltransferase 11 (LPLAT11)/membrane-bound O-acyltransferase 7 (MBOAT7), the loss of which causes cortical atrophy in humans and mice. Here, we show that LPLAT11 deficiency impaired indirect neurogenesis in the developing neocortex, resulting in fewer layer II-V neurons. LPLAT11-deficient radial glial cells had defects in differentiation into intermediate progenitor cells and increased apoptosis. Prior to these anomalies, LPLAT11 deficiency caused a fragmentation of the Golgi apparatus, accompanied by impaired apical trafficking of E-cadherin, and deregulated apical detachment. Moreover, impaired PI acyl chain remodeling led to a decreased amount of PI(4,5)P2, leading to Golgi apparatus fragmentation. Thus, these results clarify the underlying mechanism of cortical atrophy by LPLAT11 deficiency and highlight the critical role of arachidonic acid in PI in the integrity of radial glial cells.
Generators of the frequency-following response in the subthalamic nucleus: implications for non-invasive deep brain stimulation
Authors: Hnazaee Mansoureh Fahimi , Zhao Haifeng , Hao Shenglin , Moorkens Aline , Lambert Christian , Zhan Shikun , Li Dianyou , Sun Bomin , Litvak Vladimir , Cao Chunyan
Published: May 2024

While Deep Brain Stimulation (DBS) is effective treatment for several movement disorders, non-invasive stimulation modes have major clinical relevance. We report on a novel method holding potential for non-invasive subthalamic nucleus (STN) stimulation. We used an auditory frequency-following response task (FFR), a popular tool for studying the auditory brainstem as the neural response in the cortical and midbrain generator, as it precisely reflects the ongoing dynamics of a speech or non-speech sound. We recorded EEG and DBS electrodes from 5 patients, in 4 from the STN, and one from the anterior thalamus and a number of cortical and subcortical areas located in the hippocampus and frontal regions, during an FFR at a frequency higher than the upper limit of phase-locking in the cortex (333Hz). Our results revealed a neural response local to the STN, but not other structures. This finding is novel. Auditory perception in the basal ganglia is rather unexplored, and the STN generator of the FFR has likely gone unseen due to the limitations of our tools and research focus. The potential clinical implications are far-reaching. Future research should investigate whether auditory stimuli at common electrical stimulation frequencies and waveforms of electrical DBS stimulation can induce clinical improvement.
Endogenous opioid system modulates proximal and distal threat signals in the human brain
Authors: Seppälä Kerttu , Putkinen Vesa , Harju Harri , Rebelos Eleni , Hirvonen Jussi , Helin Semi , Rajander Johan , Karlsson Henry K. , Saunavaara Jani , Hyönä Jukka , Nummenmaa Lauri
Published: May 2024

BACKGROUND

Fear promotes rapid detection of threats and appropriate fight-or-flight responses. The endogenous opioid system modulates responses to pain and psychological stressors. Opioid agonists also have also anxiolytic effects. Fear and anxiety constitute major psychological stressors for humans, yet the contribution of the opioid system to acute human fear remains poorly characterized.

METHODS

We induced intense unconditioned fear in the subjects by gradually exposing them to a living constrictor snake (threat trials) versus an indoor plant (safety trials). Brain haemodynamic responses were recorded from 33 subjects during functional magnetic resonance imaging (fMRI). In addition, 15 subjects underwent brain positron emission tomography (PET) imaging using [11C]carfentanil, a high affinity agonist radioligand for μ-opioid receptors (MORs). PET studies under threat or safety exposure were performed on separate days. Pupillary arousal responses to snake and plant exposure were recorded in 36 subjects. Subjective fear ratings were measured throughout the experiments.

RESULTS

Self-reports and pupillometric responses confirmed significant experience of fear and autonomic activation during the threat trials. fMRI data revealed that proximity with the snake robustly engaged brainstem defense circuits as well as thalamus, dorsal attention network, and motor and premotor cortices. These effects were diminished during repeated exposures. PET data revealed that [11C]carfentanil binding to MORs was significantly higher during the fear versus safety condition, and the acute haemodynamic responses to threat were dependent on baseline MOR binding in the cingulate gyrus and thalamus. Finally, baseline MOR tone predicted dampening of the haemodynamic threat responses during the experiment.

CONCLUSIONS

Preparatory response during acute fear episodes involves a strong motor component in addition to the brainstem responses. These haemodynamic changes are coupled with a deactivation of the opioidergic circuit, highlighting the role of MORs in modulating the human fear response.
A survival-critical role forDrosophilagiant interneurons during predation
Authors: Chai Cynthia M. , Morrow Carmen M. , Parikh Dhyey D. , von Reyn Catherine R. , Leonardo Anthony , Card Gwyneth M.
Published: May 2024

Large axon-diameter descending neurons are metabolically costly but transmit information rapidly from sensory neurons in the brain to motor neurons in the nerve cord. They have thus endured as a common feature of escape circuits in many animal species where speed is paramount. Though often considered isolated command neurons triggering fast-reaction-time, all-or-none escape responses, giant neurons are just one of multiple parallel pathways enabling selection between behavioral alternatives. Such degeneracy among escape circuits makes it unclear if and how giant neurons benefit prey fitness. Here we competedDrosophila melanogasterflies with genetically-silenced Giant Fibers (GFs) against flies with functional GFs in an arena with wild-caught damselfly predators and find that GF silencing decreases prey survival. Kinematic analysis of damselfly attack trajectories shows that decreased prey survival fitness results from GF-silenced flies failing to escape during predator attack speeds and approach distances that would normally elicit successful escapes. When challenged with a virtual looming predator, fly GFs promote survival by enforcing selection of a short-duration takeoff sequence as opposed to reducing reaction time. Our findings support a role for the GFs in promoting prey survival by influencing action selection as a means to enhance escape performance during realistically complex predation scenarios.
Voluntary adolescent alcohol exposure does not robustly increase adulthood consumption of alcohol in multiple mouse and rat models
Authors: Sicher Avery R. , Liss Andrea , Vozella Valentina , Marsland Paige , Seemiller Laurel R. , Springer Matthew , Starnes William D. , Griffith Keith R. , Smith Grace C. , Astefanous Amy , Deak Terrence , Roberto Marisa , Varodayan Florence P. , Crowley Nicole A.
Published: May 2024

Adolescence is a period of increased risk taking, including increased alcohol and drug use. Multiple clinical studies report a positive relationship between adolescent alcohol consumption and risk of developing an alcohol use disorder (AUD) in adulthood. However, few preclinical studies have attempted to tease apart the biological contributions of adolescent alcohol exposure, independent of other social, environmental, and stress factors, and studies that have been conducted show mixed results. Here we use several adolescent voluntary consumption of alcohol models, conducted across four labs in three institutes and with two rodent species, to investigate the ramifications of adolescent alcohol consumption on adulthood alcohol consumption in controlled, pre-clinical environments. We consistently demonstrate a lack of robust increases in adulthood alcohol consumption. This work highlights that risks seen in both human datasets and other murine drinking models may be due to unique social and environmental factors – some of which may be unique to humans.

HIGHLIGHTS

Adolescent drinking-in-the-dark (DID) binge drinking does not increase adulthood consumption in a DID model or a two bottle choice model in male and female SST-Cre:Ai9 mice

Adolescent pair-housed intermittent access consumption of alcohol does not increase adulthood consumption in an identical adulthood model in male and female C57BL/6J mice

Adolescent intermittent access to alcohol does not increase adulthood consumption in male and female Wistar or Fischer 344 rats

These complementary datasets across murine models, labs and institutions highlight the need to consider human social factors as well as biological factors