bluuebunny/crossref_metadata_2025 huggingface dataset:
Widespread post-transcriptional regulation of co-transmission
Authors: Chen Nannan , Zhang Yunpeng , Rivera-Rodriguez Emmanuel J. , Yu Albert D. , Hobin Michael , Rosbash Michael , Griffith Leslie C.
Published: March 2023

While neurotransmitter identity was once considered singular and immutable for mature neurons, it is now appreciated that one neuron can release multiple neuroactive substances (co-transmission) whose identities can even change over time. To explore the mechanisms that tune the suite of transmitters a neuron releases, we developed transcriptional and translational reporters for cholinergic, glutamatergic, and GABAergic signaling inDrosophila. We show that many glutamatergic and GABAergic cells also transcribe cholinergic genes, but fail to accumulate cholinergic effector proteins. Suppression of cholinergic signaling involves posttranscriptional regulation of cholinergic transcripts by the microRNA miR-190; chronic loss of miR-190 function allows expression of cholinergic machinery, reducing and fragmenting sleep. Using a “translation-trap” strategy we show that neurons in these populations have episodes of transient translation of cholinergic proteins, demonstrating that suppression of co-transmission is actively modulated. Posttranscriptional restriction of fast transmitter co-transmission provides a mechanism allowing reversible tuning of neuronal output.

One-Sentence Summary

Cholinergic co-transmission in large populations of glutamatergic and GABAergic neurons in theDrosophilaadult brain is controlled by miR-190.
CD8+ cells and small viral reservoirs facilitate post-ART control of SIV in Mauritian cynomolgus macaques
Authors: Harwood Olivia E. , Matschke Lea M. , Moriarty Ryan V. , Balgeman Alexis J. , Weaver Abigail J. , Ellis-Connell Amy L. , Weiler Andrea M. , Winchester Lee C. , Fletcher Courtney V. , Friedrich Thomas C. , Keele Brandon F. , O’Connor David H. , Lang Jessica D. , Reynolds Matthew R. , O’Connor Shelby L.
Published: March 2023

Sustainable HIV remission after antiretroviral therapy (ART) withdrawal, or post-treatment control (PTC), remains a top priority for HIV treatment. We observed surprising PTC in an MHC-haplomatched cohort of MHC-M3+ SIVmac239+ Mauritian cynomolgus macaques (MCMs) initiated on ART at two weeks post-infection (wpi). For six months after ART withdrawal, we observed undetectable or transient viremia in seven of eight MCMs. In vivo depletion of CD8α+ cells induced rebound in all animals, indicating the PTC was mediated, at least in part, by CD8α+ cells. We found that MCMs had smaller acute viral reservoirs than a cohort of identically infected rhesus macaques, a population that rarely develops PTC. The mechanisms by which unusually small viral reservoirs and CD8α+ cell-mediated virus suppression enable PTC can be investigated using this MHC-haplomatched MCM model. Further, defining the immunologic mechanisms that engender PTC in this model may identify therapeutic targets for inducing durable HIV remission in humans.
Emotional memories are enhanced when reactivated in slow-wave sleep but impaired in REM
Authors: Yuksel Cagri , Denis Dan , Coleman James , Ren Boyu , Oh Angela , Cox Roy , Morgan Alexandra , Sato Erina , Stickgold Robert
Published: March 2023

Sleep supports memory consolidation. However, it is not completely clear how different sleep stages contribute to this process. While rapid eye movement sleep (REM) has traditionally been implicated in the processing of emotionally charged material, recent studies indicate a role for slow wave sleep (SWS) in strengthening emotional memories. Here, to directly examine which sleep stage is primarily involved in emotional memory consolidation, we used targeted memory reactivation (TMR) in REM and SWS during a daytime nap. Contrary to our hypothesis, reactivation of emotional stimuli during REM led to impaired memory. Consistent with this, REM% was correlated with worse recall in the group that took a nap without TMR. Meanwhile, cueing benefit in SWS was strongly correlated with the product of times spent in REM and SWS (SWS-REM product), and reactivation significantly enhanced memory in those with high SWS-REM product. Surprisingly, SWS-REM product was associated with better memory for reactivated items and poorer memory for non-reactivated items, suggesting that sleep both preserved and eliminated emotional memories, depending on whether they were reactivated. Notably, the emotional valence of cued items modulated both sleep spindles and delta/theta power. Finally, we found that emotional memories benefited from TMR more than did neutral ones. Our results suggest that emotional memories decay during REM, unless they are reactivated during prior SWS. Furthermore, we show that active forgetting complements memory consolidation, and both take place across SWS and REM. In addition, our findings expand upon recent evidence indicating a link between sleep spindles and emotional processing.
Oligomerization enhances huntingtin membrane activity but is suppressed by covalent crosslinking
Authors: Sedighi Faezeh , Skeens Adam , Adegbuyiro Adewale , Bard John , Siriwardhana Chathuranga , Donley Emily , Geldenhuys Werner J. , Legleiter Justin
Published: March 2023

Huntingtin disease (HD) is a neurodegenerative disease caused by expansion of a polyglutamine (polyQ) tract within the huntingtin (htt) protein, leading to aggregation into a variety of species ranging from small oligomers to large fibrils. A consensus concerning which of these aggregate states are primarily responsible for toxicity associated with mutant htt remains elusive. Htt directly binds and damages a variety of membranous surfaces within cells. Here, the ability of different aggregation states of htt to interact with and damage lipid membranes was determined. Oligomers represented the most active lipid binding species, whereas, fibril formation severely limited membrane binding. Thus, strategies to stabilize oligomers were implemented, and conformational flexibility appeared to play a key role in the oligomer/membrane interaction. In particular, stabilizing oligomers with covalent crosslinking with 1,5-difluoro-2,4-dinitrobenzene (DFDNB) effectively eliminated the ability of oligomers to bind lipid membranes and reduced their associated cellular toxicity.
The role of intraspecific crop-weed hybridization in the evolution of weediness and invasiveness: cultivated and weedy radish (Raphanus sativusL.) as a case study
Authors: Vercellino Román B. , Hernández Fernando , Presotto Alejandro
Published: March 2023

PREMISE

Crop-wild/weed hybrids usually exhibit intermediate and maladapted phenotypes compared to their parents; however, hybridization has sometimes been associated with increased fitness, potentially leading to enhanced weediness and invasiveness. Since the ecological context and maternal genetic effects may affect hybrid fitness, they could influence the evolutionary outcomes of hybridization. Here, we evaluated the performance of first-generation crop-weed hybrids ofRaphanus sativusL. and their parents under two contrasting ecological conditions.

METHODS

Using experimental hybridization and common garden experiments under field conditions, we assessed the differences in time to flowering, survival to maturity, plant biomass and reproductive components between bidirectional crop-weed hybrids and their parents, under two contrasting ecological conditions, agrestal (wheat cultivation, fertilization, weeding) and ruderal (human-disturbed uncultivated area) over two years.

RESULTS

Crop, weeds and bidirectional hybrids overlapped -at least partially-during the flowering period, indicating a high probability of gene flow. Hybrids survived to maturity at rates at least as successful as their parents and showed higher plant biomass and fecundity, which resulted in higher fitness compared to their parents in both contrasting environments, without any differences associated with the direction of the hybridization.

CONCLUSIONS

Intraspecific crop-weed hybridization, regardless of the cross direction, has the potential to promote weediness in weedyR. sativusboth in agrestal and ruderal environments, increasing the chances of the introgression of crop alleles into weed populations. This is the first report of intraspecific crop-weed hybridization inR. sativus.
Protein nonadditive expression and solubility inArabidopsishybrids and allotetraploids
Authors: June Viviana , Xu Dongqing , Papoulas Ophelia , Boutz Daniel , Marcotte Edward M. , Chen Z. Jeffrey
Published: March 2023

Interspecific hybridization in plants often leads to allopolyploids including most important crops such as wheat, cotton, and canola, while many other crops such as corn and sorghum are grown as hybrid. Both allopolyploids and hybrids show hybrid vigor or heterosis. The phenomenon has been widely applied in agriculture and extensively studied at the genetic and gene expression levels. However, proteomic changes in hybrids and polyploids remain poorly understood. Here, we report comparative analysis of soluble and insoluble proteomes inArabidopsisintraspecific and interspecific hybrids or allotetraploids formed betweenA. thalianaandA. arenosa. Both allotetraploids and intraspecific hybrids displayed nonadditive expression (unequal to the sum of the two parents) of the proteins, most of which were involved in biotic and abiotic stress responses. In the allotetraploids, homoeolog-expression bias was not observed among all proteins examined but could occur among 17-20% of the nonadditively expressed proteins, consistent with the transcriptome results. Among expression-biased homoeologs, there were moreA. thaliana-biased thanA. arenosa-biased homoeologs,. Analysis of the insoluble and soluble proteomes revealed more soluble proteins in the hybrids than their parents but not in the allotetraploids. Most proteins in ribosomal biosynthesis and in the thylakoid lumen, membrane, and stroma were in the soluble fractions, indicating a role of protein stability in photosynthetic activities for promoting growth. These results collectively support roles of nonadditive expression of stress-responsive proteins and increased solubility of photosynthetic proteins inArabidopsishybrids and allotetraploids, which may promote hybrid vigor.

Plain Language Summary

We analyzed fractionated proteomes to test protein abundance and solubility inArabidopsishybrids and polyploids. Many proteins in stress-responses are nonadditively expressed in intraspecific hybrids or allotetraploids. There are more soluble proteins of ribosomal biosynthesis and photosynthetic activities in the hybrids than in their parents but not in allotetraploids. Expression levels are equal among most protein homoeologs in the allotetraploids but are biased for ~20% of nonadditively expressed proteins. Nonadditive protein expression and solubility may play a role in heterosis.
Differential Effects of Cocaine and Morphine on the Diurnal Regulation of the Mouse Nucleus Accumbens Proteome
Authors: Ketchesin Kyle D. , Becker-Krail Darius D. , Xue Xiangning , Wilson Rashaun S. , Lam TuKiet T. , Williams Kenneth R. , Nairn Angus C. , Tseng George C. , Logan Ryan W.
Published: March 2023

Substance use disorders (SUDs) are associated with disruptions in sleep and circadian rhythms that persist during abstinence and may contribute to relapse risk. Repeated use of substances such as psychostimulants and opioids may lead to significant alterations in molecular rhythms in the nucleus accumbens (NAc), a brain region central to reward and motivation. Previous studies have identified rhythm alterations in the transcriptome of the NAc and other brain regions following the administration of psychostimulants or opioids. However, little is known about the impact of substance use on the diurnal rhythms of the proteome in the NAc. We used liquid chromatography coupled to tandem mass spectrometry-based (LC-MS/MS) quantitative proteomics, along with a data-independent acquisition (DIA) analysis pipeline, to investigate the effects of cocaine or morphine administration on diurnal rhythms of proteome in the mouse NAc. Overall, our data reveals cocaine and morphine differentially alters diurnal rhythms of the proteome in the NAc, with largely independent differentially expressed proteins dependent on time-of-day. Pathways enriched from cocaine altered protein rhythms were primarily associated with glucocorticoid signaling and metabolism, whereas morphine was associated with neuroinflammation. Collectively, these findings are the first to characterize the diurnal regulation of the NAc proteome and demonstrate a novel relationship between phase-dependent regulation of protein expression and the differential effects of cocaine and morphine on the NAc proteome.
Cis-regulatory evolution that caused change inwinglessexpression pattern associated with wing pigmentation pattern ofDrosophila
Authors: Karasawa Takumi , Saito Namiho , Koshikawa Shigeyuki
Published: March 2023

Genetic mechanisms underlying the acquisition of new traits are an important topic in evolutionary developmental biology. Especially, the co-option of important regulatory genes potentially plays an important role in the gain of new traits. However, how the co-option occurs at the sequence level is still elusive.Drosophila guttiferahas a unique wing pigmentation pattern and this is newly gained via the evolution of the expression pattern ofwingless, which induces the pigmentation pattern formation. In this study, to reveal the changes in thecis-regulatory sequence which caused the co-option ofwinglessthat lead to the expression in a new place, we conducted transgenic EGFP reporter assays of alteredcis-regulatory sequences. As a result, the sequence was divided into regions needed to activate expression in the entire wing veins and a region required for repressing expression in excess parts. Comparisons with the homologous sequence ofDrosophila melanogastershowed that the repressive function of thecis-regulatory region is also possessed byD. melanogasterwhile the activating function is newly gained in a lineage leading toD. guttifera. Furthermore, a putative binding site of SMAD transcription factors is shown to be essential for activating expression but also existing in the homologous region ofD. melanogaster. Our results suggest that the pre-existing regulatory sequences in thecis-regulatory region coordinate with the newly gained sequences to acquire the new expression pattern ofwingless.

Graphical Abstract
Bayesian Inference of a Spectral Graph Model for Brain Oscillations
Authors: Jin Huaqing , Verma Parul , Jiang Fei , Nagarajan Srikantan , Raj Ashish
Published: March 2023

The relationship between brain functional connectivity and structural connectivity has caught extensive attention of the neuroscience community, commonly inferred using mathematical modeling. Among many modeling approaches, spectral graph model (SGM) is distinctive as it has a closed-form solution of the wide-band frequency spectra of brain oscillations, requiring only global biophysically interpretable parameters. While SGM is parsimonious in parameters, the determination of SGM parameters is non-trivial. Prior works on SGM determine the parameters through a computational intensive annealing algorithm, which only provides a point estimate with no confidence intervals for parameter estimates. To fill this gap, we incorporate the simulation-based inference (SBI) algorithm and develop a Bayesian procedure for inferring the posterior distribution of the SGM parameters. Furthermore, using SBI dramatically reduces the computational burden for inferring the SGM parameters. We evaluate the proposed SBI-SGM framework on the resting-state magnetoencephalography recordings from healthy subjects and show that the proposed procedure has similar performance to the annealing algorithm in recovering power spectra and the spatial distribution of the alpha frequency band. In addition, we also analyze the correlations among the parameters and their uncertainty with the posterior distribution which can not be done with annealing inference. These analyses provide a richer understanding of the interactions among biophysical parameters of the SGM. In general, the use of simulation-based Bayesian inference enables robust and efficient computations of generative model parameter uncertainties and may pave the way for the use of generative models in clinical translation applications.
Spatial cancer systems biology resolves heterotypic interactions and identifies disruption of spatial hierarchy as a pathological driver event
Authors: Filipp Fabian V.
Published: March 2023

Spatially annotated single-cell datasets provide unprecedented opportunities to dissect cell-cell communication in development and disease. Heterotypic signaling includes interactions between different cell types and is well established in tissue development and spatial organization. Epithelial organization requires several different programs that are tightly regulated. Planar cell polarity (PCP) is the organization of epithelial cells along the planar axis, orthogonal to the apical-basal axis. Here, we investigate PCP factors and explore the implications of developmental regulators as malignant drivers. Utilizing cancer systems biology analysis, we derive a gene expression network for WNT-ligands (WNT) and their cognate frizzled (FZD) receptors in skin cutaneous melanoma. The profiles supported by unsupervised clustering of multiple-sequence alignments identify ligand-independent signaling and implications for metastatic progression based on the underpinning developmental spatial program. Omics studies and spatial biology connect developmental programs with oncological events and explain key spatial features of metastatic aggressiveness. Dysregulation of prominent PCP factors such as specific representatives of the WNT and FZD families in malignant melanoma recapitulates the development program of normal melanocytes but in an uncontrolled and disorganized fashion.
Exploring neural tracking of acoustic and linguistic speech representations in individuals with post-stroke aphasia
Authors: Kries Jill , Clercq Pieter De , Gillis Marlies , Vanthornhout Jonas , Lemmens Robin , Francart Tom , Vandermosten Maaike
Published: March 2023

Aphasia is a communication disorder that affects processing of language at different levels (e.g., acoustic, phonological, semantic). Recording brain activity via EEG while people listen to a continuous story allows to analyze brain responses to acoustic and linguistic properties of speech. When the neural activity aligns with these speech properties, it is referred to as neural tracking. Even though measuring neural tracking of speech may present an interesting approach to studying aphasia in an ecologically valid way, it has not yet been investigated in individuals with stroke-induced aphasia. Here, we explored processing of acoustic and linguistic speech representations in individuals with aphasia in the chronic phase after stroke and age-matched healthy controls. We found decreased neural tracking of acoustic speech representations (envelope and envelope onsets) in individuals with aphasia. In addition, word surprisal displayed decreased amplitudes in individuals with aphasia around 195 ms over frontal electrodes, although this effect was not corrected for multiple comparisons. These results show that there is potential to capture language processing impairments in individuals with aphasia by measuring neural tracking of continuous speech. However, more research is needed to validate these results. Nonetheless, this exploratory study shows that neural tracking of naturalistic, continuous speech presents a powerful approach to studying aphasia.

Key points

Individuals with aphasia display decreased encoding of acoustic speech properties (envelope and its onsets) in comparison to healthy controls.

Neural responses to word surprisal reveal decreased amplitudes in individuals with aphasia around 195 ms processing time (not corrected for multiple comparisons).

Neural tracking of natural speech can be used to study speech processing impairments in aphasia.
Pairing Explainable Deep Learning Classification with Clustering to Uncover Effects of Schizophrenia Upon Whole Brain Functional Network Connectivity Dynamics
Authors: Ellis Charles A. , Miller Robyn L. , Calhoun Vince D.
Published: March 2023

Many studies have analyzed resting state functional magnetic resonance imaging (rs-fMRI) dynamic functional network connectivity (dFNC) data to elucidate the effects of neurological and neuropsychiatric disorders upon the interactions of brain regions over time. Existing studies often use either machine learning classification or clustering algorithms. Additionally, several studies have used clustering algorithms to extract features related to brain states trajectories that can be used to train interpretable classifiers. However, the combination of explainable dFNC classifiers followed by clustering algorithms is highly underutilized. In this study, we show how such an approach can be used to study the effects of schizophrenia (SZ) upon brain activity. Specifically, we train an explainable deep learning model to classify between individuals with SZ and healthy controls. We then cluster the resulting explanations, identifying discriminatory states of dFNC. We lastly apply several novel measures to quantify aspects of the classifier explanations and obtain additional insights into the effects of SZ upon brain network dynamics. Specifically, we uncover effects of schizophrenia upon subcortical, sensory, and cerebellar network interactions. We also find that individuals with SZ likely have reduced variability in overall brain activity and that the effects of SZ may be temporally localized. In addition to uncovering effects of SZ upon brain network dynamics, our approach could provide novel insights into a variety of neurological and neuropsychiatric disorders in future dFNC studies.
The Human Brain Connectome Weighted by the Myelin Content and Total Intra-Axonal Cross-Sectional Area of White Matter Tracts
Authors: Nelson Mark C. , Royer Jessica , Leppert Ilana R. , Campbell Jennifer S.W. , Schiavi Simona , Jin Hyerang , Tavakol Shahin , de Wael Reinder Vos , Rodriguez-Cruces Raul , Pike G. Bruce , Bernhardt Boris C. , Daducci Alessandro , Misic Bratislav , Tardif Christine L.
Published: March 2023

A central goal in neuroscience is the development of a comprehensive mapping between structural and functional brain features. Computational models supportin vivoinvestigation of the mechanisms mediating this relationship but currently lack the requisite biological detail. Here, we characterize human structural brain networks weighted by multiple white matter microstructural features to assess their potential joint utilization in computational models. We report edge-weight-dependent spatial distributions, variance, small-worldness, rich club, hubs, as well as relationships with function, edge length and myelin. Contrasting networks weighted by the total intra-axonal cross-sectional area and myelin content of white matter tracts, we find opposite relationships with functional connectivity, an edge-length-independent inverse relationship with each other, and the lack of a canonical rich club in myelin-weighted networks. When controlling for edge length, tractometry-derived networks weighted by either tensor-based metrics or neurite density show no relationship with whole-brain functional connectivity. We conclude that structure-function brain models are likely to be improved by the co-utilization of structural networks weighted by total intra-axonal cross-sectional area and myelin content. We anticipate that the proposed microstructure-weighted computational modeling approach will support mechanistic understanding of the structure-function relationship of the human brain.

AUTHOR SUMMARY

For computational network models to provide mechanistic links between brain structure and function, they must be informed by networks in which edge weights quantify structural features relevant to brain function. Here, we characterized several weighted structural networks capturing multiscale features of white matter connectivity. We describe these networks in terms of edge weight distribution, variance and network topology, as well as their relationships with each other, edge length and function. Overall, these findings support the joint use of structural networks weighted by the total intra-axonal cross-sectional area and myelin content of white matter tracts in structure-function models. This thorough characterization serves as a benchmark for future investigations of weighted structural brain networks.
Mechanistic home range capture-recapture models for the estimation of population density and landscape connectivity
Authors: Fukasawa Keita , Higashide Daishi
Published: March 2023

Spatial capture-recapture models (SCRs) provide an integrative statistical tool for analyzing animal movement and population patterns. Although incorporating home range formation with a theoretical basis of animal movement into SCRs can improve the prediction of animal space use in a heterogeneous landscape, this approach is challenging owing to the sparseness of recapture events. In this study, we developed an advection-diffusion capture-recapture model (ADCR), which is an extension of SCRs incorporating home range formation with advection-diffusion formalism, providing a new framework to estimate population density and landscape permeability. we tested the unbiasedness of the estimator using simulated capture-recapture data generated by a step selection function. We also compared accuracy of population density estimates and home range shapes with those from SCR incorporating the least-cost path and basic SCR. In addition, ADCR was applied to real dataset of Asiatic black bear (Ursus thibetanus) in Japan to demonstrate the capacity of the ADCR to detect geographical barriers that constrain animal movements. Population density and permeability of ADCR were substantially unbiased for simulated datasets. ADCR could detect envitonmental signals on connectivity more sensitively and could estimate population density, home range shapes and size variations better than the existing models. For the application to the bear dataset, ADCR could detect the effect of water body as a barrier of movement which is consistent with previous studies, whereas estimates by SCR with the least-cost path was difficult to interplet. ADCR provides unique opportunities to elucidate both individual- and population-level ecological processes from capture-recapture data. By offering a formal link with step selection functions to estimate animal movement, it is suitable for simultaneously modeling with capture-recapture data and animal movement data. This study provides a basis for studies of the interplay between animal movement processes and population patterns.
Slitflow: a Python framework for single-molecule dynamics and localization analysis
Authors: Ito Yuma , Hirose Masanori , Tokunaga Makio
Published: March 2023

Single-molecule imaging is a promising method for direct quantification of the dynamics and distribution of biomolecules in living cells. Although numerous methods have been developed to gain biological insights into molecular behavior, the high diversity of microscopes and single-molecule dynamics can result in incomplete reproducibility of analyses. Here, we present Slitflow, an open-source framework for a single-molecule analysis workflow that includes image processing, dynamics analysis, and figure creation. We demonstrated the integrity and flexibility of the workflow using 1) a cherry-picked tracking method combining popular tools and 2) various state-of-the-art analyses in a single pipeline. The software accommodates a large variety of data and methods, paving the way for integrative analyses.

Code metadata
Sexual antagonism in sequential hermaphrodites
Authors: Hitchcock Thomas J. , Gardner Andy
Published: March 2023

Females and males may have distinct phenotypic optima, but share essentially the same complement of genes, potentially leading to trade-offs between attaining high fitness through female versus male reproductive success. Such sexual antagonism may be particularly acute in hermaphrodites, whereby both reproductive strategies are housed within a single individual. Whilst previous models have focused on simultaneous hermaphroditism, we lack theory for how sexual antagonism may play out under sequential hermaphroditism, which have the additional complexities of age-structure. Here we develop a formal theory of sexual antagonism in sequential hermaphrodites. First, we develop a general theoretical overview of the problem, then consider different types of sexually antagonistic and life-history trade-offs, under different modes of genetic inheritance (autosomal or cytoplasmic), and different forms of sequential hermaphroditism (protogynous, protoandrous or bi-directional). Finally, we provide a concrete illustration of these general patterns by developing a two-stage two-sex model, which yields conditions for both invasion of sexually antagonistic alleles and maintenance of sexually antagonistic polymorphisms.
Weather variation in objectively measured physical activity: results of four Brazilian cohorts
Authors: Martins Rafaela Costa , Blumenberg Cauane , Wendt Andrea T , de Andrade Müller Werner , Santos Iná S , Matijasevich Alicia , Domingues Marlos , Bertoldi Andréa D , Gonçalves Helen , Wehrmeister Fernando C. , Reichert Felipe Fossati
Published: March 2023

Background

The aim of the present study was to examine the relationship of objectively measured physical activity and weather variables in different stages of life course.

Methods

This study used data from four Brazilian cohorts (mean ages: 10.9, 22.6, 30.2, and 70.5 years). The exposure was weather variation, using temperature, rain, humidity, and wind velocity. The outcome measured was accelerometer based physical activity in three ways: overall, 5-minute bouts, and 10-minute bouts physical activity. Both exposure and outcome were collected from the same period. Crude and adjusted analyses were fitted using a two-part model.

Results

Among 9,966 individuals from different ages evaluated, physical activity levels were low, especially in older adults. Rain and mean wind velocity were not associated physical activity of individuals, however, the probability of children being inactive was higher during humid days. After mutually adjusting the models for weather variables, only mean temperature and humidity were associated with higher and lower physical activity levels in children, respectively.

Conclusions

Weather variables are not key indicators to be accounted when modelling physical activity studies in almost all ages. However, this study helps to identify specifically exposures, regardless of the physical activity operationalization.
The impact of early anti-SARS-CoV-2 antibody production on the length of hospitalization stay among COVID-19 patients
Authors: de Almeida Dalziza Victalina , Cezar Priscila Alves , Fernandes Thais Freitas Barreto , Schwarz Marcos Gustavo Araujo , Mendonça-Lima Leila , Giacoia-Gripp Carmem Beatriz Wagner , Côrtes Fernanda Heloise , Lindenmeyer Guimarães Monick , Pilotto Jose Henrique , de Sá Nathalia Beatriz Ramos , Cazote Andressa da Silva , Gomes Larissa Rodrigues , Quintana Marcel de Souza Borges , Ribeiro-Alves Marcelo , Coelho Lara , Geraldo Kim Mattos , Ribeiro Maria Pia Diniz , Cardoso Sandra Wagner , Grinsztejn Beatriz Gilda Jegerhom , Santos Valdiléa Gonçalves Veloso dos , Morgado Mariza Gonçalves
Published: March 2023

COVID-19 has challenged the scientific community in the search for biological markers and information that can contribute to the early management of the severe disease. Given the global scale of COVID-19, including reports of reinfection even in the presence of effective vaccines, we have not yet been able to eradicate the disease. This factor implies the emergence of new waves and an increasing number of hospitalizations. This study aimed to characterize the neutralizing antibody (Nab) geometric mean titers (GMTs) in hospitalized patients with COVID-19 and to evaluate the association with length of stay, comorbidities, and patient outcome. Among the 103 participants, 84 (81.5%) had some previous condition associated with worsening health, and 31 (30%) died. We found that neutralization potency varied greatly across individuals and was significantly higher in patients discharged before 14 days than in patients who stayed longer in the hospital. During the study period, 15 people living with HIV (PLWH) were hospitalized, and no significant difference in clinical characteristics or anti-SARS-CoV-2 Nabs was observed. However, PLWH with severe COVID-19 were younger (41.7, IQR=17.5) than other hospitalized COVID-19 patients (59.3, IQR=22,P<0.01). A high anti-HIV-1 antibody GMT of 583.9 (95% CI: 344-990) was detected, demonstrating maintenance of anti-HIV-1 Nab production among PLWH coinfected with SARS-CoV-2. Therefore, these results indicate that neutralizing antibodies are not the only immunological response capable of controlling disease progression. Nevertheless, these data highlight the importance of more Nab screening studies to predict shorter hospital stays.
A novel approach for estimating vaccine efficacy for infections with multiple outcomes: application to a COVID-19 vaccine trial
Authors: Williams Lucy R , Voysey Merryn , Pollard Andrew J , Grassly Nicholas C
Published: March 2023

Vaccines can provide protection against infection or limit disease progression and severity. Vaccine efficacy (VE) is typically evaluated independently for different outcomes, but this can cause biased estimates of VE. We propose a new analytical framework based on a model of disease progression for VE estimation for infections with multiple possible outcomes of infection: Joint analysis of multiple outcomes in vaccine efficacy trials (JAMOVET). JAMOVET is a Bayesian hierarchical regression model that controls for biases and can evaluate covariates for VE, the risk of infection, and the probability of progression. We applied JAMOVET to simulated data, and data from COV002 (NCT04400838), a phase 2/3 trial of ChAdOx1 nCoV-19 (AZD1222) vaccine. Simulations showed that biases are corrected by explicitly modelling disease progression and imperfect test characteristics. JAMOVET estimated ChAdOx1 nCoV-19 VE against infection (VEin) at 49% (95% CI 37-59) and progression to symptoms (VEpr) at 44% (95% CI 27-58). This implies a VE against symptomatic infection of 72% (95% CI 63-80), consistent with published trial estimates.VEindecreased with age whileVEprincreased with age. JAMOVET is a powerful tool for evaluating diseases with multiple dependent outcomes and can be used to adjust for biases and identify predictors of key outcomes.
The effect of bolus properties on muscle activation patterns and TMJ loading during unilateral chewing
Authors: Sagl Benedikt , Schmid-Schwap Martina , Piehslinger Eva , Yao Hai , Rausch-Fan Xiaohui , Stavness Ian
Published: March 2023

Mastication is a vital human function and uses an intricate coordination of muscle activation to break down food. Collection of detailed muscle activation patterns is complex and commonly only masseter and anterior temporalis muscle activation are recorded. Chewing is the orofacial task with the highest muscle forces, potentially leading to high temporomandibular joint (TMJ) loading. Increased TMJ loading is often associated with the onset and progression of temporomandibular disorders (TMD). Hence, studying TMJ mechanical stress during mastication is a central task. Current TMD self-management guidelines suggest eating small and soft pieces of food, but patient safety concerns inhibitin vivoinvestigations of TMJ biomechanics.

For this purpose, we have developed a state-of-the-artin silicomodel, combining rigid body bones, finite element TMJ discs and line actuator muscles. To solve the problems regarding muscle activation measurement, we used a forward dynamics tracking approach, optimizing muscle activations driven by mandibular motion. We include a total of 256 different combinations of food bolus size, stiffness and position in our study and report kinematics, muscle activation patterns and TMJ disc von Mises stress.

Computed mandibular kinematics agree well with previous measurements. The computed muscle activation pattern stayed stable over all simulations, with changes to the magnitude relative to stiffness and size of the bolus. Our results agree with the clinical guidelines regarding bolus modifications as smaller and softer food boluses lead to less TMJ loading. The results help to strengthen the confidence in TMD self-management recommendations, potentially reducing pain levels of patients.
Wireless Electrical-Molecular Quantum Signalling for Cancer Cell Induced Death
Authors: Jain Akhil , Gosling Jonathan , Liu Shaochuang , Wang Haowei , Stone Eloise M. , Pérez-García Lluïsa , Amabilino David B. , Fromhold Mark , Smith Stuart , Rahman Ruman , Long Yitao , Turyanska Lyudmila , Rawson Frankie J.
Published: March 2023

Quantum biological tunnelling for electron transfer (QBET) is involved in controlling cellular behaviour. Control of electrical-molecular communication could revolutionise the development of disruptive technologies for understanding and modulating electrically induced molecular signalling. Current communication technology is not appropriate for interfacing with cells at a spatial/temporal level equivalent to the native biological signalling. This limits our ability to tune cell function by controlling single molecular events. Here, we merge wireless nano-electrochemical tools with cancer cells. Gold-bipolar nanoelectrodes functionalised with redox active species were developed as electric field stimulated bio-actuators, that we term bio-nanoantennae. We show that a remote electrical input regulates electron transport between the redox molecules on the bio-nanoantennae in a selective manner. The wireless modulation of electron transport results in QBET triggering apoptosis in patient-derived cancer cells, representing electrical-induced induced controlled molecular signalling. Transcriptomics data highlight the electric field-induced nanoantenna targets the cancer cells in a unique manner. The insight concerning action and functional nanomaterials opens a plethora of applications in healthcare. This approach may lead to new quantum-based medical diagnostics and treatments, as well as a fundamental understanding of biological physics.
Translation dynamics in human cells visualized at high-resolution reveal cancer drug action
Authors: Xing Huaipeng , Taniguchi Reiya , Khusainov Iskander , Kreysing Jan Philipp , Welsch Sonja , Turoňová Beata , Beck Martin
Published: March 2023

Ribosomes catalyze protein synthesis by cycling through various functional states. These states have been extensively characterized in vitro, yet their distribution in actively translating human cells remains elusive. Here, we optimized a cryo-electron tomography-based approach and resolved ribosome structures inside human cells with a local resolution of up to 2.5 angstroms. These structures revealed the distribution of functional states of the elongation cycle, a Z tRNA binding site and the dynamics of ribosome expansion segments. In addition, we visualized structures of Homoharringtonine, a drug for chronic myeloid leukemia treatment, within the active site of the ribosome and found that its binding reshaped the landscape of translation. Overall, our work demonstrates that structural dynamics and drug effects can be assessed at near-atomic detail within human cells.

One-Sentence Summary

Snapshots of ribosome dynamics at near-atomic resolution within native and drug-treated human cells are revealed.
Direct link between convergent evolution at sequence level and phenotypic level of septal pore cap in Agaricomycotina
Authors: Iizuka Tomoyo , Nozawa Masafumi , Ikeo Kazuho
Published: March 2023

Several apparently homologous morphological characters are known to have independently evolved in different lineages multiple times. However, the genetic backgrounds of such morphological convergences are not well understood. To detect any correlated genes potentially responsible for morphological convergence at the phenotypic level, we focused on the morphology of the septal pore cap (SPC), which is involved in mycelia’s complex multicellularity in fungi. SPCs are classified into three morphological types: perforate, imperforate, and vesiculate. To understand what evolutionary events occurred at the sequence level during morphological convergence of perforate SPCs in Agaricomycotina, we examined sequence differences between species with different SPC types by comparative genomic analysis. If sequences from species with perforate SPCs formed a cluster, the associated gene might be involved in generating perforate SPCs in multiple lineages. Based on this assumption, we detected eight candidate genes, including an SPC-related gene,spc33. The results showed that some amino acid substitutions independently occurred in both lineages in which species with perforate SPCs emerged. From these results, we speculate that the amino acid substitutions inspc33were critical in the emergence of perforate SPCs in multiple lineages. We also found thatspc33evolved just before imperforate SPC emergence based on homology search ofspc33and the species phylogeny. These findings illustrate the first step to clarifying the genetic basis of SPC morphological evolution. Our study contributes to both clarifying the genetic basis of morphological convergence and pioneering our understanding of fungal evolutionary morphology.
Estimating cortical thickness trajectories in children across different scanners using transfer learning from normative models
Authors: Gaiser C. , Berthet P. , Kia S.M. , Frens M. A. , Beckmann C. F. , Muetzel R. L. , Marquand A.
Published: March 2023

This work illustrates the use of normative models in a longitudinal neuroimaging study of children aged 6-17 years and demonstrates how such models can be used to make meaningful comparisons in longitudinal studies, even when individuals are scanned with different scanners across successive study waves. More specifically, we first estimated a large-scale reference normative model using hierarchical Bayesian regression from N=40,435 individuals across the lifespan and from dozens of sites. We then transfer these models to a longitudinal developmental cohort (N=5,985) with three measurement waves acquired on two different scanners that were unseen during estimation of the reference models. We show that the use of normative models provides individual deviation scores that are independent of scanner effects and efficiently accommodate inter-site variations. Moreover, we provide empirical evidence to guide the optimization of sample size for the transfer of prior knowledge about the distribution of regional cortical thicknesses. We show that a transfer set containing as few as 25 samples per site can lead to good performance metrics on the test set. Finally, we demonstrate the clinical utility of this approach by showing that deviation scores obtained from the transferred normative models are able to detect and chart morphological heterogeneity in individuals born pre-term.
Reentrant condensation of a multicomponent complex system of biomolecules induced by polyphosphate
Authors: Furuki Tomohiro , Nobeyama Tomohiro , Suetaka Shunji , Matsui Ryokei , Fukuoka Tatsuhiko , Arai Munehito , Shiraki Kentaro
Published: March 2023

Reentrant condensation (RC) is a phase behavior of protein solution comprising at least two components. In RC, a protein state varies from one phase to two phases and then back to one phase as the concentration of one component monotonically increases. To understand the phase behavior of multicomponent complex solutions of biomolecules, it is worth constructing an experimental multicomponent system that exhibits RC behavior. Here, we used a cola/milk mixture to investigate RC of a multicomponent complex system and explained the RC mechanism by reducing the system to two pure components, polyphosphate (polyP) and casein. In the multicomponent complex system, RC was observed with 20–60% cola and 1% milk. In the pure system, RC occurred with 0.01–2 mM tetraphosphate and 0.5 mg/ml casein. Moreover, the phase diagram showed that the condensation of casein depended on the chain length of the polyP. The present study succeeded in experimentally inducing RC in a multicomponent system and reproducing RC even when the system was reduced to its pure components. The fact that RC can be experimentally induced using common materials will provide important insights into the understanding of phase-separation behavior of biomolecules.
A Practical Approach to Constructing a Knowledge Graph for Soil Ecological Research
Authors: Le Guillarme Nicolas , Thuiller Wilfried
Published: March 2023

With the rapid accumulation of biodiversity data, data integration has emerged as a hot topic in soil ecology. Data integration has indeed the potential to advance our knowledge of global patterns in soil biodiversity by facilitating large-scale meta-analytical studies of soil ecosystems. However, ecologists are still poorly equipped when it comes to integrating disparate datasets into a unified knowledge graph with well-defined semantics. This paper presents a practical approach to constructing a knowledge graph from heterogeneous and distributed (semi-)structured data sources. To illustrate our approach, we integrate several datasets on the trophic ecology of soil organisms into a trophic knowledge graph and show how information can be retrieved from the graph to support multi-trophic studies.