bluuebunny/crossref_metadata_2025 huggingface dataset:
Phylogenomics of the psychoactive mushroom genusPsilocybeand evolution of the psilocybin biosynthetic gene cluster
Authors: Bradshaw Alexander J , Ramírez-Cruz Virginia , Awan Ali R. , Furci Giuliana , Guzmán-Dávalos Laura , Stamets Paul , Dentinger Bryn T.M.
Published: December 2022

Psychoactive mushrooms in the genusPsilocybehave immense cultural value and have been used for centuries in Mesoamerica. Despite a recent surge in interest in these mushrooms due to emerging evidence that psilocybin, the main psychoactive compound, is a promising therapeutic for a variety of mental illnesses, their phylogeny and taxonomy remain substantially incomplete. Moreover, the recent elucidation of the psilocybin biosynthetic gene cluster is known for only five species ofPsilocybe, four of which belong to only one of two major clades. We set out to improve the phylogeny forPsilocybeusing shotgun sequencing of 71 fungarium specimens, including 23 types, and conducting phylogenomic analysis using 2,983 single-copy gene families to generate a fully supported phylogeny. Molecular clock analysis suggests the stem lineage arose ∼66 mya and diversified ∼53 mya. We also show that psilocybin biosynthesis first arose inPsilocybe, with 4–5 possible horizontal transfers to other mushrooms between 40 and 22 mya. Moreover, predicted orthologs of the psilocybin biosynthetic genes revealed two distinct gene orders within the cluster that corresponds to a deep split within the genus, possibly consistent with the independent acquisition of the cluster. This novel insight may predict differences in chemistry between the two major clades of the genus, providing further resources for the development of novel therapeutics.
Embedding-based alignment: combining protein language models and alignment approaches to detect structural similarities in the twilight-zone
Authors: Pantolini Lorenzo , Studer Gabriel , Pereira Joana , Durairaj Janani , Schwede Torsten
Published: December 2022

Language models are now routinely used for text classification and generative tasks. Recently, the same architectures were applied to protein sequences, unlocking powerful tools in the bioinformatics field. Protein language models (pLMs) generate high dimensional embeddings on a per-residue level and encode the “semantic meaning” of each individual amino acid in the context of the full protein sequence. Multiple works use these representations as a starting point for downstream learning tasks and, more recently, for identifying distant homologous relationships between proteins. In this work, we introduce a new method that generates embedding-based protein sequence alignments (EBA), and show how these capture structural similarities even in the twilight zone, outperforming both classical sequence-based scores and other approaches based on protein language models. The method shows excellent accuracy despite the absence of training and parameter optimization. We expect that the association of pLMs and alignment methods will soon rise in popularity, helping the detection of relationships between proteins in the twilight-zone.
Identification of a second site for coat protein binding in bacteriophage P22 scaffolding protein
Authors: Dedeo Corynne L. , Whitehead Richard D. , Teschke Carolyn M.
Published: December 2022

Scaffolding proteins are essential for the assembly of most tailed, double-stranded DNA bacteriophages as well as herpesviruses. These proteins interact specifically with the coat proteins to efficiently assemble procapsids with the correct morphology. A helix-turn-helix (HTH) domain of bacteriophage P22 scaffolding protein is essential for coat binding, but the presence of additional coat protein binding sites has been predicted. An alanine substitution at scaffolding protein residue L245 causes a strong cold-sensitive phenotype. Bothin vivoandin vitroassembly with L245A scaffolding protein yields aberrant and petite particles at non-permissive temperatures. The L245A scaffolding protein is destabilized as determined by thermal melts monitored by circular dichroism. Through crosslinking studies, residue L245 interacts with the coat protein A-domain residue D198, which has been predicted previously to contain a scaffolding protein binding site. L245 also binds R101 in the coat protein P-domain as well as E18 in the N-arm. These results demonstrate the presence of secondary coat binding sites that may function in conjunction with the HTH domain to promote the assembly of procapsids with the correct curvature.

Importance

Many dsDNA viruses, including tailed bacteriophages and Herpesviruses, assemble precursor capsids, or procapsids, using an essential catalytic scaffolding protein. How scaffolding proteins induce proper assembly of their major capsid proteins remains unclear. The scaffolding protein of bacteriophage P22 has a C-terminal helix-turn-helix domain that interacts with the N-arm of the coat protein to activate it for assembly. Here, a second potential coat protein interaction site is identified in scaffolding protein at residue L245. Residue L245 may be involved in stabilizing a small helical domain based the effect of the substitution scaffolding protein stability and a predicted model of the scaffolding protein fold, thereby indicating additional complexity in the interaction between coat and scaffolding proteins.
Brain sodium MRI-derived priors support the estimation of epileptogenic zones using personalized model-based methods in Epilepsy
Authors: Azilinon Mikhael , Wang Huifang E. , Makhalova Julia , Zaaraoui Wafaa , Ranjeva Jean-Philippe , Bartolomei Fabrice , Guye Maxime , Jirsa Viktor
Published: December 2022

Epilepsy patients with drug-resistant epilepsy are eligible for surgery aiming to remove the regions involved in the production of seizure activities (the so-called epileptogenic zone network (EZN). Thus the accurate estimation of the EZN is crucial. A data-driven, personalized virtual brain models derived from patient-specific anatomical and functional data are used in Virtual Epileptic Patient (VEP) to estimate the EZN via optimization methods from Bayesian inference. The Bayesian inference approach used in previous VEP integrates priors, based on the features of stereotactic-electroencephalography (SEEG) seizures’ recordings. Here, we propose new priors, based on quantitative23Na-MRI. The23Na-MRI data were acquired at 7T and provided several features characterizing the sodium signal decay. The hypothesis is that the sodium features are biomarkers of neuronal excitability related to the EZN and will add additional information to VEP estimation. In this paper, we first proposed the mapping from23Na-MRI features to predict the EZN via a machine learning approach. Then, exploiting these predictions as priors in the VEP pipeline, we demonstrated that23Na-MRI prior based VEP estimation of the EZN improved the results in terms of balanced accuracy and as good as SEEG priors in terms of the weighted harmonic mean of the precision and recall.

AUTHOR SUMMARY

For the first time quantitative23Na-MRI were used as prior information to improve estimation of EZN using the model-based method of VEP pipeline. The priors were based on logistic regression predictions of the EZN, using23Na-MRI features as predictors. The23Na-MRI priors inferred EZNs significantly closer to the clinical hypotheses - in terms of balanced accuracy - than the previously used priors or the no-prior condition.
Impact of COVID-19 and the postponement of the Tokyo 2020 Paralympic Games on Paralympic athletes and staff: A cross-sectional study
Authors: Walter Matthias , Mesa Adam , McCracken Laura A. , Barakso Carolyn , Buker Daniel Bueno , González Pablo Benavides , Holtz Wanda , Jaeger Conchita , Nightingale Tom E. , Krassioukov Andrei V.
Published: December 2022

We aimed to investigate the impact of the postponement of the Tokyo 2020 Paralympic Games on expected participants’ careers, COVID-19 history and mental health using an e-survey. Thirty-nine participants (median age 37 years; 16 females) from five countries responded between July 20thand September 28th, 2021, of which 37 completed the survey, including 20 athletes and 11 coaches. All but two participants planned to attend the rescheduled Games in 2021 (95%). Ninety percent (35/39) had previously tested at least once for COVID-19, with six testing positive. While three had no symptoms, all six were moderately impacted. Scores (median; lower and upper quartiles; questionnaire) for depression (2; 0.75-4; PHQ-9) and anxiety (2; 0-5.25; GAD-7) were low. Scores for post-traumatic stress disorder (PTSD) (3.5; 1-11; IES-R) were also low, but four participants reported high scores indicative of clinical concern for PTSD. There was low emotional distress caused by postponement of the Games (2; 1-4.5), and moderately low fear of catching COVID-19 (3; 2-5.5) on 10-point (0 = none, 10 = extreme) rating scales. While overall this population appears relatively resilient, the postponement of the Games came at a cost for some athletes and coaches, specifically with regards to experiencing symptoms of PTSD.
Non-Nutritive Suckling System for Real-Time Characterization of Intraoral Vacuum Profile in Full Term Neonates
Authors: Truong Phuong , Walsh Erin , Scott Vanessa P. , Coleman Todd , Tilvawala Gopesh , Friend James
Published: December 2022

Infant breastfeeding diagnostics remain subjective due to the absence of instrumentation to objectively measure and understand infant oral motor skills and suckling characteristics. Qualitative diagnostic exams, such as the digital suck assessment which relies upon a clinician’s gloved finger inserted into the infant’s mouth, produce a diversity of diagnoses and intervention pathways due to their subjective nature. In this paper, we report on the design of a non-nutritive suckling (NNS) system which quantifies and analyzes quantitative intraoral vacuum and sucking patterns of full-term neonates in real time. In our study, we evaluate thirty neonate suckling profiles to demonstrate the technical and clinical feasibility of the system. We successfully extract the mean suck vacuum, maximum suck vacuum, frequency, burst duration, number of sucks per burst, number of sucks per minute, and number of bursts per minute. In addition, we highlight the discovery of three intraoral vacuum profile shapes that are found to be correlated to different levels of suckling characteristics. These results establish a framework for future studies to evaluate oromotor dysfunction that affect the appearance of these signals based on established normal profiles. Ultimately, with the ability to easily and quickly capture intraoral vacuum data, clinicians can more accurately perform suckling assessments to provide timely intervention and assist mothers and infants towards successful breastfeeding outcomes.
Mushroom body output neurons MBONa1/a2 define an odor intensity channel that regulates behavioral odor discrimination learning in larvalDrosophila
Authors: Mohamed Abdulkadir , Malekou Iro , Sim Timothy , O’Kane Cahir J. , Maait Yousef , Scullion Benjamin , Masuda-Nakagawa Liria M.
Published: December 2022

The sensitivity of animals to sensory input must be regulated to ensure that signals are detected and also discriminable. However, how circuits regulate the dynamic range of sensitivity to sensory stimuli is not well understood. A given odor is represented in the insect mushroom bodies (MBs) by sparse combinatorial coding by Kenyon cells (KCs), forming an odor quality representation. To address how intensity of sensory stimuli is processed at the level of the MB input region, the calyx, we characterized a set of novel mushroom body output neurons that respond only to high odor concentrations.

We show that a pair of MB calyx output neurons, MBONa1/2, are postsynaptic in the MB calyx, where they receive extensive synaptic inputs from KC dendrites, the inhibitory feedback neuron APL, and octopaminergic sVUM1 neurons, but relatively few inputs from projection neurons. This pattern is broadly consistent in the third instar larva as well as in the first instar connectome. MBONa1/a2 presynaptic terminals innervate a region immediately surrounding the MB medial lobe output region in the ipsilateral and contralateral brain hemispheres. By monitoring calcium activity using jRCamP1b, we find that MBONa1/a2 responses are odor-concentration dependent, responding only to ethyl acetate (EA) concentrations higher than a 200-fold dilution, in contrast to MB neurons which are relatively concentration-invariant and respond to EA dilutions as low as 10−4. Optogenetic activation of the calyx-innervating sVUM1 modulatory neurons originating in the SEZ (Subesophageal zone), did not show a detectable effect on MBONa1/a2 odor responses. Optogenetic activation of MBONa1/a2 using CsChrimson impaired odor discrimination learning compared to controls. We propose that MBONa1/a2 form an output channel of the calyx, summing convergent sensory and modulatory input, firing only to high odor concentration, and might affect the activity of downstream MB targets.
Conserved and cell type-specific transcriptional responses to IFN-γ in the ventral midbrain
Authors: Hobson Benjamin D. , Stanley Adrien T. , De Los Santos Mark B. , Culbertson Bruce , Mosharov Eugene V. , Sims Peter A. , Sulzer David
Published: December 2022

Dysregulated inflammation within the central nervous system (CNS) contributes to neuropathology in infectious, autoimmune, and neurodegenerative disease. With the exception of microglia, major histocompatibility complex (MHC) proteins are virtually undetectable in the mature, healthy central nervous system (CNS). Neurons have generally been considered incapable of antigen presentation, and although interferon gamma (IFN-γ) can elicit neuronal MHC class I (MHC-I) expression and antigen presentationin vitro, it remains unclear whether similar responses occurin vivo. Here we directly injected IFN-γ into the ventral midbrain of mature mice and analyzed gene expression profiles of specific CNS cell types. We find that IFN-γ induces cellular proliferation and expression of MHC-II and associated genes only in microglia. However, IFN-γ upregulated MHC-I and associated mRNAs in ventral midbrain microglia, astrocytes, oligodendrocytes, and GABAergic, glutamatergic, and dopaminergic neurons. The core set of IFN-γ-induced genes and their response kinetics were conserved across neurons and glia, with a lower amplitude of expression in neurons. A diverse repertoire of genes was upregulated in glia, particularly microglia, while no neuron-specific responses to IFN-γ were observed. Using mutant mice to selectively delete the IFN-γ-binding domain of IFNGR1 in dopaminergic neurons, we demonstrate that dopaminergic neurons respond directly to IFN-γ. Our results suggest that most neurons are capable of responding directly to IFN-γ and upregulating MHC-I and related genesin vivo, but their expression amplitude and repertoire is limited compared to oligodendrocytes, astrocytes, and microglia.

One-sentence summary

We find that IFN-γ induces transcription of MHC class I antigen processing and presentation machinery in all major parenchymal cell types in the ventral midbrain; however, neuronal responses are low amplitude and limited to a small set of genes, MHC class II expression and cellular proliferation are restricted to microglia, and dopamine neuronal responses require cell autonomous expression of IFNGR1.
Habitual ground nesting in the Bugoma Forest chimpanzees (Pan troglodytes schweinfurthii), Uganda
Authors: Hobaiter Catherine , Klein Harmonie , Gruber Thibaud
Published: December 2022

We report the presence of habitual ground nesting in a newly studied East African chimpanzee(Pan troglodytes schweinfurthii)population in the Bugoma Central Forest Reserve, Uganda. Across a 2-year period we encountered 891 night-nests, 189 of which were classified as ground nests, a rate of ∼21%. We find no preliminary evidence of socio-ecological factors that would promote its use and highlight local factors, such as high incidence of forest disturbance due to poaching and logging, which appear to make its use disadvantageous. While further study is required to establish whether this behaviour meets the strict criteria for non-human animal culture, we support the argument that the wider use of population and group-specific behavioural repertoires in flagship species, such as chimpanzees, offers a tool to promote the urgent conservation action needed to protect threatened ecosystems, including the Bugoma forest.
Low-cost gold-leaf electrode as a platform forEscherichia coliimmuno-detection
Authors: Podunavac Ivana , Kukkar Manil , Léguillier Vincent , Rizzotto Francesco , Pavlovic Zoran , Janjušević Ljiljana , Costache Vlad , Radonic Vasa , Vidic Jasmina
Published: December 2022

Gold electrodes are one of most prevalent substrates in electrochemical biosensors because they can be easily and highly efficiently functionalized with thiolated biomolecules. However, conventional methods to fabricate gold electrodes are costly, time consuming and require onerous equipment. Here, an affordable method for rapid fabrication of an electrochemical immune-sensor forEscherichia colidetection is presented. The gold electrode was generated using 24-karat gold leaves and low-cost polyvinyl chloride adhesive sheets covered with an insulating PTFE layer. The gold-leaf electrode (GLE) was patterned using laser ablation and characterized by cyclic voltammetry, electrochemical impedance spectroscopy, scanning electronic microscopy, contact angle and 3D profiling. The GLEs were modified by a self-assembled mercaptopropionic monolayer, followed by surface activation to allow binding of the specific anti-E. coliantibody via carbodiimide linking. The biosensor showed a detection limit of 2 CFU/ml and a linear dynamic range of 10 – 107CFU/ml forE. colicells. No false positive signals were obtained from control bacteria. The obtained results demonstrated suitability of GLE for use in biosensors with high reliability and reproducibility. It is foreseeable that our work will inspire design of point-of-need biosensors broadly applicable in low-resource settings.
Perceptual awareness is gradual in temporal and dichotomous in fronto-parietal cortices
Authors: Solanas Marta Poyo , Zhan Minye , de Gelder Beatrice
Published: December 2022

Two major issues in consciousness research concern the measuring methods that determine perceptual unawareness and whether consciousness is a gradual or an ‘all-or-nothing’ phenomenon. This 7T fMRI study addresses both questions using a continuous flash suppression paradigm with an emotional recognition task (fear vs neutral bodies) in combination with the perceptual awareness scale. Behaviorally, recognition sensitivity increased linearly with increased stimuli awareness and was at chance level during perceptual unawareness. Threat expressions triggered a slower heart rate than neutral ones during ‘almost clear’ experience of the stimulus, indicating freezing behavior. The activity in occipital, temporal, parietal and frontal regions as well as in amygdala increased with increased stimulus awareness while the activity in early visual areas showed the opposite pattern. The relationship between temporal area activity and perceptual awareness was better characterized by a gradual model while the activity in fronto-parietal areas by a dichotomous model, suggesting different roles in conscious processing. Interestingly, no evidence of non-conscious processing was found in amygdala as well as no significant effect of emotion, in disagreement with the functions long ascribed to this subcortical structure.
Spatially heterogeneous structure-function coupling in haemodynamic and electromagnetic brain networks
Authors: Liu Zhen-Qi , Shafiei Golia , Baillet Sylvain , Misic Bratislav
Published: December 2022

The relationship between structural and functional connectivity in the brain is a key question in connectomics. Here we quantify patterns of structure-function coupling across the neocortex, by comparing structural connectivity estimated using diffusion MRI with functional connectivity estimated using both neurophysiological (MEG-based) and haemodynamic (fMRI-based) recordings. We find that structure-function coupling is heterogeneous across brain regions and frequency bands. The link between structural and functional connectivity is generally stronger in multiple MEG frequency bands compared to resting state fMRI. Structure-function coupling is greater in slower and intermediate frequency bands compared to faster frequency bands. We also find that structure-function coupling systematically follows the archetypal sensorimotor-association hierarchy, as well as patterns of laminar differentiation, peaking in granular layer IV. Finally, structure-function coupling is better explained using structure-informed inter-regional communication metrics than using structural connectivity alone. Collectively, these results place neurophysiological and haemodynamic structure-function relationships in a common frame of reference and provide a starting point for a multi-modal understanding of structure-function coupling in the brain.
Lectin-Seq: a method to profile lectin-microbe interactions in native communities
Authors: McPherson Robert L. , Isabella Christine R. , Walker Rebecca L. , Sergio Dallis , Gaca Tony , Raman Smrithi , Nguyen Le Thanh Tu , Wesener Darryl A. , Halim Melanie , Wuo Michael , Dugan Amanda , Kerby Robert , Ghosh Soumi , Rey Federico E. , Vlamakis Hera , Alm Eric J. , Xavier Ramnik J. , Kiessling Laura L.
Published: December 2022

Soluble human lectins are critical components of innate immunity. Genetic models suggest lectins influence host-resident microbiota, but their specificity for commensal and mutualist species is understudied. Elucidating lectins’ roles in regulating microbiota requires understanding which microbial species they bind within native communities. To profile human lectin recognition, we developed Lectin-Seq. We apply Lectin-Seq to human fecal microbiota using mannose-binding lectin (MBL) and intelectin-1 (hItln1). The microbial interactomes of MBL and hItln1 differ in composition and diversity. MBL binding is highly selective for a small subset of species commonly associated with humans. In contrast, hItln1’s interaction profile encompasses a broad range of lower-abundance species. Thus, human lectins have evolved to recognize distinct species of commensals, suggesting they directly influence microbiome composition. Lectin-Seq offers a new means of annotating microbial communities.

One-Sentence Summary

Soluble human lectins bind distinct bacterial species in fecal microbiota.
The feedback loop of thetransformergene results in proper feminization under multiple sex determination signals in the ant,Vollenhovia emeryi
Authors: Miyakawa Misato Okamoto , Miyakawa Hitoshi
Published: December 2022

Organisms that reproduce sexually have evolved highly sophisticated mechanisms to generate two sexes. Some hymenopterans (such as ants, bees, and wasps) have a complementary sex-determination system in which heterozygosity at one CSD locus induces female development, whereas hemi- or homozygosity at the locus induces male development. This system can generate a high cost of inbreeding, as individuals that are homozygous at the locus become sterile, diploid males. On the other hand, some hymenopterans have evolved a multi-locus, complementary, sex-determination system in which heterozygosity in at least one CSD locus induces female development. This system effectively reduces the proportion of sterile diploid males; however, how multiple primary signals pass through a molecular cascade to regulate the terminal sex-determination gene has remained unclear. To clarify this matter, we investigated the molecular cascade in the ant,Vollenhovia emeryi, with two CSD loci. Here we show thattransformer(tra) is necessary for proper feminization. Expression and functional analysis showed that individuals heterozygous in at least one of the two CSD loci develop into females. Individuals heterozygous at only a single CSD locus do not develop into sexual intermediates, because the signal derived from the heterozygous CSD is amplified by a positive-feedback splicing loop oftra. Our data also demonstrate thattracontrols splicing ofdoublesex(dsx), which is involved in sexual differentiation. We suggest a cascade model to arrive at a binary determination of sex under multiple primary signals.
Paradoxical improvement of cognitive control in older adults under dual-task walking conditions is associated with more flexible reallocation of neural resources: A Mobile Brain-Body Imaging (MoBI) study
Authors: Patelaki Eleni , Foxe John J. , Mantel Emma P. , Kassis George , Freedman Edward G.
Published: December 2022

Combining walking with a demanding cognitive task is traditionally expected to elicit decrements in gait and/or cognitive task performance. However, it was recently shown that, in a cohort of young adults, most participants ‘paradoxically’ improved performance when walking was added to performance of a Go/NoGo response inhibition task. The present study aims to extend these previous findings to an older adult cohort, to investigate whether this paradoxical improvement when dual-tasking is observed in healthy older adults. Mobile Brain/Body Imaging (MoBI) was used to record electroencephalographic (EEG) activity, three-dimensional (3D) gait kinematics and behavioral responses in the Go/NoGo task, during sitting or walking on a treadmill, in 34 young adults and 37 older adults. Increased response accuracy during walking, independent of age, was found to correlate with slower responses to stimuli and with walking-related EEG amplitude modulations over latencies and topographies related to the cognitive component of inhibition. On the other hand, aging, independent of response accuracy during walking, was found to correlate with slower treadmill walking speeds and attenuation in walking-related EEG amplitude modulations over latencies and topographies associated with the motor component of inhibition. Older adults whose response accuracy improved during walking manifested neural signatures of both behavioral improvement and aging, suggesting that their flexibility in reallocating neural resources while walking might be maintained for the cognitive but not for the motor inhibitory component. These distinct neural signatures of aging and behavior can potentially be used to identify ‘super-agers’, or individuals at risk for cognitive decline due to aging or neurodegenerative disease.
Age-associated downregulation of glutamate and GABA neurotransmission-related gene expression in the rostral ventrolateral medulla of male Fischer 344 rats
Authors: Balivada Sivasai , Tapia Geronimo P. , Pawar Hitesh N. , Khan Arshad M. , Kenney Michael J.
Published: December 2022

The rostral ventrolateral medulla (RVLM), a part of the medullary reticular formation, plays a major role in several physiological responses, including cardiovascular and sympathetic nervous system functions. Although aging causes disturbances in the responses of these physiological systems, RVLM involvement in these age-related changes is not clear. Previous work using high-throughput gene expression analysis of the RVLM in aged animals suggested that chemical neurotransmission-related genes might be downregulated with advancing age. Since RVLM function involves a balance of signals from inhibitory and excitatory inputs, which is largely mediated by gamma-aminobutyric acid (GABA) and excitatory amino acid (EAA) neurotransmission, we hypothesized that aging is associated with altered excitatory and/or inhibitory neurotransmission-related gene expression in the RVLM. To test this hypothesis, we micropunched an RVLM-containing area from young (3–5 months), middle-aged (12–14 months), and aged (22– 26 months) Fischer 344 male rats. RNA purified from these micropunches was analyzed using GABA and Glutamate RT2Profiler PCR arrays (n= 8–10). Each profiler array has primers for 84 GABA and glutamate neurotransmission related genes. In addition, the expression of selected genes was validated at the RNA level using TaqMan®based-qPCR and at the protein level using western blotting. All the genes that displayed significant differential expression (1.5-fold,p< .05, FDR < .05) were identified to be downregulated in the RVLM of aged and middle-aged rats compared to young rats. This downregulation did not appear to be a result of RVLM tissue sampling differences among the age groups, since a separate validation of our sampling method, which involved careful mapping of micropunched regions to a standardized brain atlas, revealed no spatial differences in sampled sites among age groups. Among the downregulated genes, the percentage of glutamate neurotransmission-related genes was higher than GABA neurotransmission-related genes. The Solute carrier family 1 member 6 (Slc1a6) gene showed the highest fold downregulation at the RNA level in the RVLM of aged compared to young rats, and its protein product, Excitatory amino acid transporter 4 (EAAT4), showed a downregulatory trend in the RVLM of aged and middle-aged rats. These results suggest that molecular constituents of both GABA and glutamate neurotransmission might be altered in the RVLM of aged and middle-aged rats, and the changes in glutamate neurotransmission might be more prominent. Investigating age-associated anatomical and functional changes in RVLM GABA and glutamate neurotransmission might provide a foundation for understanding the effects of aging on physiological function.
Quantifying physiological trait variation with automated hyperspectral imaging in rice
Authors: Ting To-Chia , Souza Augusto , Imel Rachel K. , Guadagno Carmela R. , Hoagland Chris , Yang Yang , Wang Diane R.
Published: December 2022

Advancements in hyperspectral imaging (HSI) and establishment of dedicated plant phenotyping facilities have enabled researchers to gather large quantities of plant spectral images with the aim of inferring target phenotypes non-destructively. However, large volumes of data that result from HSI and corequisite specialized methods for analysis may prevent plant scientists from taking full advantage of these systems. Here, we explore estimation of physiological traits in 23 rice accessions using an automated HSI system. Under contrasting nitrogen conditions, HSI data are used to classify treatment groups with ≥ 83% accuracy by utilizing support vector machines. Out of the 14 physiological traits collected, leaf-level nitrogen content (N, %) and carbon to nitrogen ratio(C:N)could also be predicted from the hyperspectral imaging data with normalized root mean square error of predictions smaller than 14% (R2of 0.88 forNand 0.75 forC:N).This study demonstrates the potential of using an automated HSI system to analyze genotypic variation for physiological traits in a diverse panel of rice; to help lower barriers of application of hyperspectral imaging in the greater plant science research community, analysis scripts used in this study are carefully documented and made publicly available.

HIGHLIGHT

Data from an automated hyperspectral imaging system are used to classify nitrogen treatment and predict leaf-level nitrogen content and carbon to nitrogen ratio during vegetative growth in rice.
Multi-modal multi-resolution atlas of the human neonatal cerebral cortex based on microstructural similarity
Authors: Li Mingyang , Xu Xinyi , Cao Zuozhen , Chen Ruike , Zhao Ruoke , Zhao Zhiyong , Dang Xixi , Oishi Kenichi , Wu Dan
Published: December 2022

The neonatal period is a critical window for the development of the human brain and may hold implications for the long-term development of cognition and disorders. Multi-modal connectome studies have revealed many important findings underlying the adult brain but related studies were rare in the early human brain. One potential challenge is the lack of an appropriate and unbiased parcellation that combines structural and functional information in this population. Using 348 multi-modal MRI datasets from the developing human connectome project, we found that the information fused from the structural, diffusion, and functional MRI was relatively stable across MRI features and showed high reproducibility at the group level. Therefore, we generated automated multi-resolution parcellations (300 - 500 parcels) based on the similarity across multi-modal features using a gradient-based parcellation algorithm. In addition, to acquire a parcellation with high interpretability, we provided a manually delineated parcellation (210 parcels), which was approximately symmetric, and the adjacent areas around each boundary were statistically different in terms of the integrated similarity metric and at least one kind of original features. Overall, the present study provided multi-resolution and neonate-specific parcellations of the cerebral cortex based on multi-modal MRI properties, which may facilitate future studies of the human connectome in the early development period.
Estimating measures to reduce the transmission of SARS-CoV-2 in Australia to guide a ‘National Plan’ to reopening
Authors: Ryan Gerard E. , Shearer Freya M. , McCaw James M. , McVernon Jodie , Golding Nick
Published: December 2022

The availability of COVID-19 vaccines promised a reduction in the severity of disease and relief from the strict public health and social measures (PHSMs) imposed in many countries to limit spread and burden of COVID-19. We were asked to define vaccine coverage thresholds for Australia’s transition to easing restrictions and reopening international borders. Using evidence of vaccine effectiveness against the then-circulating Delta variant, we used a mathematical model to determine coverage targets. The absence of any COVID-19 infections in many sub-national jurisdictions in Australia posed particular methodological challenges. We used a novel metric called Transmission Potential (TP) as a proxy measure of the population-level effective reproduction number. We estimated TP of the Delta variant under a range of PHSMs, test-trace-isolate-quarantine (TTIQ) efficiencies, vaccination coverage thresholds, and age-based vaccine allocation strategies. We found that high coverage across all ages (≥70%) combined with ongoing TTIQ and minimal PHSMs was sufficient to avoid lockdowns. At lesser coverage (≤60%) rapid case escalation risked overwhelming of the health sector or the need to reimpose stricter restrictions. Maintaining low case numbers was most beneficial for health and the economy, and at higher coverage levels (≥80%) further easing of restrictions was deemed possible. These results directly informed easing of COVID-19 restrictions in Australia.
Prevalence of salivary anti-SARS-CoV-2 IgG antibodies in vaccinated children
Authors: Badano María Noel , Duarte Alejandra , Salamone Gabriela , Sabbione Florencia , Pereson Matias , Chuit Roberto , Baré Patricia
Published: December 2022

Vaccination against COVID-19 has mitigated the impact of SARS-CoV-2 infection, decreasing the probability of progression to severe disease and death in vaccinated people.

Parallel to the development and administration of COVID-19 vaccines, the immune response induced by the different vaccine platforms has been investigated, mainly, in the adult population. However, since the approval of the vaccines for use in pediatric individuals was a posteriori, vaccination began later in this population. This, added to the difficulty in obtaining blood samples from pediatric individuals, has led to less knowledge about the humoral immune response following vaccination in children.

In this work, we analyzed the humoral response induced by vaccination in children through a non-invasive approach such as the measurement of specific salivary antibodies. Our results showed a high prevalence of specific salivary antibodies (81%), with the highest levels of antibodies being observed in those children who had three doses, a greater number of exposures and a shorter interval time between the last exposure to SARS-CoV-2 antigens and saliva collection. These results agree with those reported for the systemic humoral immune response in vaccinated adults, suggesting the administration of booster doses in children to maintain high antibody levels.

Therefore, determination of salivary antibodies against SARS-CoV-2 could be a non-invasive tool for disease surveillance, vaccination follow-up and to assist vaccination strategies against COVID-19.
Dynamic Biobanking for Advancing Breast Cancer Research
Authors: Abdollahyan Maryam , Gadaleta Emanuela , Asif Millahat , Oscanoa Jorge , Barrow-McGee Rachel , Jones Samantha , Jones Louise , Chelala Claude
Published: December 2022

Longitudinal patient biospecimens and data advance breast cancer research through enabling precision medicine approaches for identifying risk, early diagnosis, improved disease management and targeted therapy. Cancer biobanks must evolve to provide not only access to high-quality annotated biospecimens and rich associated data, but also the tools required to harness these data. We present the Breast Cancer Now Tissue Bank centre at the Barts Cancer Institute as an exemplar of a dynamic biobanking ecosystem that hosts and links longitudinal biospecimens and multimodal data including electronic health records, genomic and imaging data, offered alongside integrated data sharing and analytics tools. We demonstrate how such an ecosystem can inform precision medicine efforts in breast cancer research.

We present the infrastructure established for the Breast Cancer Now Tissue Bank centre at the Barts Cancer Institute as an exemplar of a dynamic biobank that supports precision medicine for breast cancer through providing access to integrated data and tools, and could serve as a blueprint for future cancer biobanks.
Prevalence and antimicrobial sensitivity patterns of uropathogens, in Tikur Anbessa specialized hospital emergency department Addis Ababa, Ethiopia
Authors: Boru Yared , Shelton Dominick , Azazh Aklilu , Engida Hywet , Kifle Fitsum , Debebe Finot
Published: December 2022

Background

Empirical treatment of infections remains a major contributing factor to the emergence of pathogens that are resistant to antibiotics. The study aimed to assess the prevalence and anti-microbial sensitivity patterns of uropathogens in the emergency center of Tikur Anbessa Hospital, Ethiopia.

Methods

Urine sample data collected over two years from January 2015 to January 2016 at Tikur Anbessa Hospital’s laboratory were retrospectively analyzed for bacterial pathogens, and their antimicrobial susceptibility. Antimicrobial sensitivity tests were done using the disc diffusion technique as per the standard of the Kirby-Bauer method.

Result

Of the total 220 samples that were collected, 50 (22.7%) were culture-positive. Male to female data ratio was 1:1.1. Escherichia coli was the dominant isolate (50%) followed by Enterococcus species (12%), Enterobacter species (12%), and Klebsiella species (8%). Overall resistance rates to Cotrimoxazole, Ampicillin, Augmentin, and Ceftriaxone were 90.4%, 88.8%, 82.5%, and 79.3%, respectively. The sensitivity rates for Chloramphenicol, Amikacin, Vancomycin, Meropenem, Cefoxitin, and Nitrofurantoin ranged from 72% - 100%. The antibiogram of isolates showed that 43 (86%) isolates were resistant to two or more antimicrobials, and 49 (98%) were resistant to at least one antibiotic.

Conclusion and recommendation

Urinary tract infections are mostly caused by Gram-negative bacteria predominantly in females and Escherichia coli are the most common isolates. Resistance rates to Cotrimoxazole, Ampicillin, Augmentin, and Ceftriaxone were high. Chloramphenicol, Amikacin, Vancomycin, Meropenem, Cefoxitin, and Nitrofurantoin are considered appropriate antimicrobials for the empirical treatment of urinary tract infections in the emergency department. Yet, using antibiotics indiscriminately for patients with complicated UTIs may increase the resistance rate and also lead to treatment failure, hence the prescriptions should be revised following the culture and sensitivity results
Cannabinoids Exposure Levels and its Relation to Anxiety Symptoms and Sleep Disturbances: A Scoping Review Protocol
Authors: Perez-Carreño Juan Guillermo , Vaddiparti Krishna , Castaneda Elizabeth , Garcia Gabriela A. , Gupta Pranav Sai , Lopez-Quintero Catalina
Published: December 2022

At least 60% of individuals with anxiety disorders report sleep disturbances. Shared physiological mechanisms might explain their co-occurrence. Scientific literature related to medical cannabis, a promising therapeutical candidate for these conditions, increased about 15 times in the last 10 years. However, assessments of cannabinoid exposure, anxiety, and sleep are inconsistent across studies, and the quality of the evidence is not often evaluated. We developed a Scoping Review to examine the current knowledge on these gaps related to cannabinoid use for anxiety and sleep disturbances.

This protocol provides detailed information on how the scoping review will be conducted. It shows the inclusion criteria for studies on the topic of interest as well as the search strategies for the following databases: PubMed, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, LILACS, and PsycINFO. We present the methodological aspects for screening, data extraction, and data charting. In addition, we proposed to evaluate the quality of the evidence by applying critical appraisal tools according to the study designs.

Adherence to this protocol will allow the research team to effectively and reliably synthesize research evidence on the effect of cannabinoids on anxiety symptoms and sleep disturbances.
Omicron-associated mortality for principal causes other than COVID-19, including mortality with a confirmed SARS-CoV-2 infection, and ICU admissions with an Omicron infection in adults aged over 60 years in France
Authors: Goldstein Edward
Published: December 2022

Background

With the emergence of the Omicron variant, an increasing proportion of SARS-CoV-2 associated deaths have a principal cause of death other than COVID-19. In France, between Nov. 1, 2021 --July 31, 2022, in addition to 33,353 deaths with the principal cause of COVID-19, there were 9,638 deaths with a confirmed SARS-CoV-2 infection with a principal cause of death other than COVID-19 (as well as SARS-CoV-2-associated deaths with an undetected SARS-CoV-2 infection).

Methods

We examined the relation between mortality for COVID-19, mortality for other causes, and ICU admissions with a SARS-CoV-2-infection in adults aged over 60y in France.

Results

The number of deaths with principal causes other than COVID-19 in France between July 2021-June 2022 was greater than the corresponding number between July 2020-June 2021 by 20,860 (95% CI (11241,30421)) after adjusting for pre-pandemic trends in mortality (compared to the increase of 3,078 in the number of deaths with a SARS-CoV-2 infection with principal causes other than COVID-19 between the two time periods). During the period of Omicron circulation (Nov. 1, 2021 - Nov. 13, 2022), there was a strong association between the rates of ICU admission with a SARS-CoV-2 infection in adults aged over 60y and (a) rates of COVID-19 deaths (correlation=0.96 (0.92,0.97)); (b) rates of mortality with principal causes other than COVID-19 (correlation=0.89 (0.82,0.94)). Proportions of ICU admissions for causes other than COVID-19 among all ICU admissions with a SARS-CoV-2 infection in older adults were lower during the periods when rates of COVID-19 disease in the community were higher.

Conclusions

The significant increase in mortality with principal causes other than COVID-19, as well as the decreases in the proportions of ICU admissions for causes other than COVID-19 among all ICU admissions with a SARS-CoV-2 infection in older adults during the periods when rates of COVID-19 disease in the community were higher suggest under-detection of Omicron infections in associated complications that did not manifest themselves as COVID-19, which is related to the treatment of SARS-CoV-2 infection in those complications.
Protocol for a prospective cohort study on the feasibility of application of nutritional ultrasound in the diagnosis and follow-up of patients with nutritional risk at hospital discharge: Study on body composition and function (DRECO)
Authors: García Almeida José Manuel , Guerrero Diego Bellido , de Luis Román Daniel , Rolo Germán Guzmán , Olveira Gabriel
Published: December 2022

Background

The application of nutritional ultrasound for the morphological and structural study of muscle mass is an emerging technique in clinical nutrition. Currently, all definitions of malnutrition include the measurement of muscle mass involvement, however, there is no single way to assess it. It is necessary to develop new techniques to identify muscle involvement in malnutrition that are valid, standardized, reliable, accurate and profitable.

Objectives

The objective of this study is to value the new muscle ultrasound techniques aimed to measure muscle and functional status, to make a more accurate diagnosis and a better prediction of complications and morbidity and mortality in patients at nutritional risk. Primary outcome: to assess the feasibility of ultrasound or muscle ultrasound techniques in both nutritional diagnosis and follow-up, over 3 to 6 months, in a nutritional intervention program.

Methods

DRECO (Disease-Related caloric-protein malnutrition EChOgraphy) is a prospective, multicenter, uncontrolled clinical study in standard clinical practice to value the usefulness of nutritional ultrasound (muscle ultrasound) in the nutritional diagnosis and follow-up of patients over a period of 3 to 6 consecutive months, after standard nutritional clinical practice intervention, and physical activity to control their disease-related malnutrition.

Discussion

This study will standardize nutritional ultrasound measures. It will validate and define specific cut-off values for nutritional ultrasound and get its correlation with already well-known nutritional tools such as SGA (Subjective Global Assessment) or GLIM (Global Leadership Initiative on Malnutrition) criteria. Thus, muscle ultrasound will become not only a tool to assess the diagnosis of malnutrition, but it will be integrated in the routine clinical practices to evaluate nutritional interventions.

Registration

This study is registered atclinicaltrials.gov(NCT05433831), registered on June 27th, 2022.https://clinicaltrials.gov/ct2/show/NCT05433831.
Identification of a key genetic factor governing arabinan utilization in the gut microbiome suggests a novel therapeutic target for constipation
Authors: Zhang Chengcheng , Yu Leilei , Ma Chenchen , Jiang Shuaiming , Wang Shunhe , Tian Fengwei , Xue Yuzheng , Zhao Jianxin , Zhang Hao , Liu Liming , Chen Wei , Huang Shi , Zhang Jiachao , Zhai Qixiao
Published: December 2022

Probiotics have been widely used to improve impaired gastro-intestinal motility, yet their efficacy varied substantially across strains. Here, by a large-scale genetic screen plusin vivomeasurements, we identified a key genetic factor (abfAcluster governing arabinan utilization) in probioticBifidobacterium longumharnessing the treatment efficacy against functional constipation (FC). Intriguingly, it also presents in a range of gut resident microbiota and played a protective role against FC. Next, our longitudinal multi-omics study in humans revealed that the exogenousabfA-cluster- carryingB. longumcan well establish itself in the gut, and enrich arabinan-utilization residents and beneficial metabolites (e.g., acetate, butyrate, chenodeoxycholic acid and uracil). Finally, transplantation ofabfA-cluster-enriched human microbiota to FC- induced germ-free mice recapitulated the marked gut-motility improvement and elevated production of beneficial metabolites. Collectively, our proof-of-concept study actively demonstrated a critical yet underexplored role of microbialabfAcluster in ameliorating FC, establishing generalizable principles for developing functional-genomics-directed probiotic therapies.