bluuebunny/crossref_metadata_2025_split huggingface dataset:
Task-dependent and automatic tracking of hierarchical linguistic structure
Authors: Oever Sanne Ten , Carta Sara , Kaufeld Greta , Martin Andrea E. 
Published: February 2022

AbstractLinguistic phrases are tracked in sentences even though there is no clear acoustic phrasal marker in the physical signal. This phenomenon suggests an automatic tracking of abstract linguistic structure that is endogenously generated by the brain. However, all studies investigating linguistic tracking compare conditions where either relevant information at linguistic timescales is available, or where this information is absent altogether (e.g., sentences versus word lists during passive listening). It is therefore unclear whether tracking at these phrasal timescales is related to the content of language, or rather, is a consequence of attending to the timescales that happen to match behaviourally-relevant information. To investigate this question, we presented participants with sentences and word lists while recording their brain activity with MEG. Participants performed passive, syllable, word, and word-combination tasks corresponding to attending to rates they would naturally attend to, syllable-rates, word-rates, and phrasal-rates, respectively. We replicated overall findings of stronger phrasal-rate tracking measured with mutual information (MI) for sentences compared to word lists across the classical language network. However, in the inferior frontal gyrus (IFG) we found a task-effect suggesting stronger phrasal-rate tracking during the word-combination task independent of the presence of linguistic structure, as well as stronger delta-band connectivity during this task. These results suggest that extracting linguistic information at phrasal-rates occurs automatically with or without the presence of an additional task, but also that that IFG might be important for temporal integration across various perceptual domains.
Functional, transcriptional, and microbial shifts associated with healthy pulmonary aging: insights from rhesus macaques
Authors: Rhoades Nicholas S. , Davies Michael , Lewis Sloan A. , Cinco Isaac R. , Kohama Steven G. , Bermudez Luiz E. , Winthrop Kevin L. , Fuss Cristina , Mattison Julie A. , Spindel Eliot R. , Messaoudi Ilhem 
Published: February 2022

ABSTRACTOlder individuals are at increased risk of developing severe respiratory infections due to age-related changes in the immunological, microbial, and functional landscape of the lung. However, our understanding of the impact of age on the respiratory tract remains limited as samples from healthy humans are challenging to obtain and confounding variables such as smoking and environmental pollutant exposure make it difficult to assess the true impact of aging. On the other hand, studies in rodent models are biased by their specific pathogen free status. In this study, we utilize a rhesus macaque model of healthy aging to examine the functional, immunological, and microbial consequences of aging in the lung. Pulmonary function testing in this large (n=34 adult, n=49 aged) cross-sectional study established age and sex differences similar to humans supporting the translational accuracy of this model. Additionally, an increased abundance of myeloid cells (alveolar and infiltrating macrophages) and a concomitant decrease in T-cells were also observed in aged animals. Single cell RNA sequencing indicated a transcriptional shift in the pulmonary CD8+ T-cell population from GRZMB expressing cells to IFN expressing cells, while frequency of IL-1B expressing alveolar macrophages was significantly reduced. Interestingly, the lung microbiome of many animals was dominated by a single microbe, Tropheryma spp., the prevalence of which decreased with age. These data provide a comprehensive picture of the functional, microbial and immunological changes of the lung in healthy macaque aging and provide insight into the increased prevalence and severity of respiratory disease in the elderly.
Inhibitory NPY neurons provide a large and heterotopic commissural projection in the inferior colliculus
Authors: Anair Justin D. , Silveira Marina A. , Mirjalili Pooyan , Beebe Nichole L. , Schofield Brett R. , Roberts Michael T. 
Published: February 2022

AbstractLocated in the midbrain, the inferior colliculus (IC) plays an essential role in many auditory computations, including speech processing and sound localization. The right and left side of the IC are interconnected by a dense fiber tract, the commissure of the IC (CoIC), that provides each IC with one its largest sources of input (i.e., the contralateral IC). Despite its prominence, the CoIC remains poorly understood. Previous studies using anterograde and retrograde tract-tracing showed that IC commissural projections are predominately homotopic and tonotopic, targeting mirror-image locations in the same frequency region in the contralateral IC. However, it is unknown whether specific classes of neurons, particularly inhibitory neurons which constitute ∼10-40% of the commissural projection, follow this pattern. We therefore examined the commissural projections of Neuropeptide Y (NPY) neurons, the first molecularly identifiable class of GABAergic neurons in the IC. Using retrograde tracing with Retrobeads in NPY-hrGFP mice of both sexes, we found that NPY neurons comprise ∼11% of the commissural projection. Moreover, focal injections of Retrobeads showed that NPY neurons in the central nucleus of the IC exhibit a more divergent and heterotopic commissural projection pattern than non-NPY neurons. Thus, commissural NPY neurons are positioned to provide cross-frequency, lateral inhibition to the contralateral IC. Through this circuit, sounds that drive activity in limited frequency bands on one side of the IC might suppress activity across a larger number of frequency bands in the contralateral IC.
Testicular Dysgenesis Syndrome-like morphology and gene expression, and activation of Hypoxia Inducible Factor 1 Alpha in juvenile lamb testes following developmental exposure to low-level environmental chemical mixture
Authors: Elcombe Chris S. , Monteiro Ana , Elcombe Matthew R. , Ghasemzadeh-Hasankolaei Mohammad , Evans Neil P. , Bellingham Michelle 
Published: February 2022

AbstractCurrent declines in male reproductive health may, in part, be driven by anthropogenic environmental chemical exposure. Using the biosolid treated pasture (BTP) sheep model, this study examined the effects of gestational exposure to a translationally relevant mixture of environmental chemicals. At 8 weeks of age, ram lambs gestationally exposed to BTP were lighter than control, and their testes contained fewer germ cells and had a greater proportion of Sertoli-cell-only seminiferous tubules. Effects of biosolid exposure on the testicular transcriptome correlated with human testicular dysgenesis syndrome (TDS) patient data. Common differentially expressed genes indicated changes in apoptotic and mTOR signalling, which concurs with previous gene expression data from neonatal BTP lambs. Gene expression data and immunohistochemistry indicates increased HIF1α activation and nuclear localisation in BTP exposed animals, known to disrupt testosterone synthesis. Together, these results provide a potential mechanism for the pathogenesis of this phenotype, and TDS in humans.
Multinuclear MRI reveals early efficacy of stem cell therapy in stroke
Authors: Helsper Shannon , Yuan Xuegang , Bagdasarian F. Andrew , Athey Jacob , Li Yan , Borlongan Cesario V. , Grant Samuel C. 
Published: February 2022

AbstractCompromised adult human mesenchymal stem cells (hMSC) can impair cell therapy efficacy and further reverse ischemic recovery. However,in vitroassays require extended passage to characterize cells, limiting rapid assessment for therapeutic potency. Multinuclear magnetic resonance imaging and spectroscopy (MRI/S) provides near real-time feedback on disease progression and tissue recovery. Applied to ischemic stroke,23Na MRI evaluates treatment efficacy within 24 h after middle cerebral artery occlusion, showing recovery of sodium homeostasis and lesion reduction in specimens treated with hMSC while1H MRS identifies reduction in lactate levels. This combined metric was confirmed by evaluating treatment groups receiving healthy or compromised hMSC versus control (sham saline injection) over 21 d. Behavioral tests to assess functional recovery and cell analysis for immunomodulatory and macrophage activity to detect hMSC potency confirm MR findings. Clinically, these MR metrics may prove critical to early evaluations of therapeutic efficacy and overall stroke recovery.
Convolutional networks can model the functional modulation of the MEG responses associated with feed-forward processes during visual word recognition
Authors: van Vliet Marijn , Rinkinen Oona , Shimizu Takao , Niskanen Anni-Mari , Devereux Barry , Salmelin Riitta 
Published: February 2022

AbstractNeuroimaging studies have provided a wealth of information about when and where changes in brain activity might be expected during reading. We sought to better understand the computational steps that give rise to such task-related modulations of neural activity by using a convolutional neural network to model the macro-scale computations necessary to perform single-word recognition. We presented the model with stimuli that had been shown to human volunteers in an earlier magnetoencephalography (MEG) experiment and evaluated whether the same experimental effects could be observed in both brain activity and model. In a direct comparison between model and MEG recordings, the model accurately predicted the amplitude changes of three evoked MEG response components commonly observed during single-word reading. In contrast to traditional models of reading, our model directly operates on the pixel values of an image containing text. This allowed us to simulate the whole gamut of processing from the detection and segmentation of letter shapes to word-form identification, with the deep learning architecture facilitating inclusion of a large vocabulary of 10k Finnish words. Interestingly, the key to achieving the desired behavior was to use a noisy activation function for the units in the model as well as to obey word frequency statistics when repeating stimuli during training. We conclude that the deep learning techniques that revolutionized models of object recognition can also create models of reading that can be straightforwardly compared to neuroimaging data, which will greatly facilitate testing and refining theories on language processing in the brain.
Assessing agreement between different polygenic risk scores in the UK Biobank
Authors: Clifton Lei , Collister Jennifer A , Liu Xiaonan , Littlejohns Tom J , Hunter David J 
Published: February 2022

1.AbstractPolygenic risk scores (PRS) are proposed to be used in clinical and research settings for risk stratification. However, there are limited investigations on how different PRS diverge from each other for risk prediction of individuals.We compared two recently published PRS for each of three conditions, breast cancer, hypertension and dementia, to assess the stability of running these algorithms for risk prediction in a single large population. We used imputed genotyping data from the UK Biobank (UKB) prospective cohort, limited to the White British subset.We found that:Only 65%-79% of SNPs in the first PRS were represented in the more recent PRS for all three diseases, after having taken linkage disequilibrium (LD) into account (R2 >0.8).Although the difference in the area under the received operator curve (AUC) obtained using the two PRS is hardly appreciable for all three diseases, there were large differences in individual risk prediction between the two PRS.We found substantial discordance between different PRS for the same disease, indicating that individuals could receive different medical advice depending on which PRS is used to assess their genetic susceptibility. It is desirable to resolve this uncertainty before using PRS for risk stratification in clinical settings.
Exon variants associated with asthma and allergy1
Authors: Wjst Matthias 
Published: February 2022

AbstractRecent biobank based exon sequencing studies included thousands of traits while the mutational spectrum of asthma and allergy associated genes is still unknown.MethodsMeta-analysis of exome data from 281,104 UK Biobank samples that were analyzed for association of mostly rare variants with asthma, allergic rhinitis and atopic dermatitis. Variants of interest (VOI) were tabulated, shared genes annotated and compared to earlier GWAS, WGBS, WES and selected candidate gene studies.Results354 VOI were significantly associated with the traits examined. They cluster mainly in two large regions on chromosome 6 and 17 while there is basically no overlap of atopic dermatitis with both other diseases. After exclusion of the two atopic dermatitis variants, 321 unique VOI remain in 122 unique genes. 30 genes are shared by the group of 87 genes with increased and the group of 65 genes with decreased risk for allergic disease. 85% of genes identified earlier by common SNPs in GWAS can not be replicated.DiscussionMost identified genes are involved in interferon γ and IL33 signaling pathway. They highlight already known but also new pharmacological targets, including the IL33 receptor ST2/IL1RL1, TLR1, ALOX15, GSDMA, BTNL2, IL13 and IKZF3. Future pharmacological studies will need to included these VOI for stratification of the study population.
Motor cortical influence relies on task-specific activity covariation
Authors: Warriner Claire L. , Fageiry Samaher , Saxena Shreya , Costa Rui M. , Miri Andrew 
Published: February 2022

SUMMARYDuring limb movement, spinal circuits facilitate the alternating activation of antagonistic flexor and extensor muscles. Yet antagonist cocontraction is often required to stabilize joints, like when loads are handled. Previous results suggest that these different muscle activation patterns are mediated by separate flexion- and extension-related motor cortical output populations, while others suggest recruitment of task-specific populations. To distinguish between hypotheses, we developed a paradigm in which mice toggle between forelimb tasks requiring antagonist alternation or cocontraction and measured activity in motor cortical layer 5b. Our results conformed to neither hypothesis: consistent flexion- and extension-related activity was not observed across tasks, and no task-specific populations were observed. Instead, activity covariation among motor cortical neurons dramatically changed between tasks, thereby altering the relation between neural and muscle activity. This was also observed specifically for corticospinal neurons. Collectively, our findings indicate that motor cortex drives different muscle activation patterns via task-specific activity covariation.HIGHLIGHTSMice perform two forelimb tasks involving distinct antagonist muscle activity in a novel paradigmL5b motor cortical neurons are not organized by task-specific activityL5b motor cortical neurons do not encode muscle activity consistently across tasksTask-specific muscle activity is driven by a change in motor cortical activity covariationeTOC BLURBWarriner et al. simultaneously measured muscle and motor cortical activity in mouse during antagonist forelimb muscle alternation and cocontraction, revealing that these distinct muscle activation patterns are not driven through consistent flexion and extension programs nor through the activity of discrete, task-specific neuronal subsets. Instead, distinct patterns involve task-specific changes in firing pattern covariation among layer 5b neurons, and corticospinal neurons in particular, which change their relationship to muscle activity across tasks.
Quantitative live-cell imaging of secretion activity reveals dynamic immune responses
Authors: Yamagishi Mai , Miyata Kaede , Kamatani Takashi , Kabata Hiroki , Baba Rie , Tanaka Yumiko , Suzuki Nobutake , Matsusaka Masako , Motomura Yasutaka , Kiniwa Tsuyoshi , Koga Satoshi , Goda Keisuke , Ohara Osamu , Funatsu Takashi , Fukunaga Koichi , Moro Kazuyo , Uemura Sotaro , Shirasaki Yoshitaka 
Published: February 2022

AbstractThe measurement of cytokine secretions has contributed to the development of immunology; however, new methods that enable highly sensitive and efficient analysis are required for the precise characterisation of dynamic secretion activity when using rare cells or limited human specimens. Here, we report a new technology for quantitative live-cell imaging of secretion activity (qLCI-S), that enables high-throughput and dual-colour detection of prolonged secretion activity at the single-cell level, followed by transcriptome analysis for individual cells based on their phenotype. The power of the qLCI-S was demonstrated by visualising the individual and longitudinal cytokine secretion patterns of group 2 innate lymphoid cells, which comprised <0.01% human peripheral blood mononuclear cells, and identifying their minor subpopulations. This new technology will provide new insights into the spatiotemporal dynamic nature of various secretory functions and the development of fundamental tools for phenotypic drug discovery and regenerative and precision medicine.
Recapitulation of Human Pathophysiology and Identification of Forensic Biomarkers in a Translational Swine Model of Chlorine Inhalation Injury
Authors: Achanta Satyanarayana , Gentile Michael A. , Albert Carolyn J. , Schulte Kevin A. , Pantazides Brooke G. , Crow Brian S. , Quiñones-González Jennifer , Perez Jonas W. , Ford David A. , Patel Rakesh P. , Blake Thomas A. , Gunn Michael D. , Jordt Sven E. 
Published: February 2022

AbstractRationaleChlorine gas (Cl2) has been repeatedly used as a chemical weapon, first in World War I and most recently in Syria. Life-threatening Cl2exposures frequently occur in domestic and occupational environments, and in transportation accidents. There is a knowledge gap in large animal models of Cl2-induced acute lung injury (ALI) required to accurately model human etiology and for the development of targeted countermeasuresObjectiveTo develop a translational model of Cl2-induced ALI in swine to study toxico-pathophysiology and identify biomarkers useful for forensic analysis.MethodsSpecific pathogen-free Yorkshire swine (30-40 kg) of either sex were exposed to Cl2gas (≤ 240 ppm for 1 h) or filtered air under anesthesia and controlled mechanical ventilation.ResultsExposure to Cl2resulted in severe hypoxia and hypoxemia, increased airway resistance and peak inspiratory pressure, and decreased dynamic lung compliance. Chlorine exposure resulted in increased total BALF and neutrophil counts, vascular leakage, and edema compared to the control group. The model recapitulated all three key histopathological features of human ALI, such as neutrophilic alveolitis, deposition of hyaline membranes, and formation of microthrombi. Free and lipid-bound 2-chlorofatty acids and chlorotyrosine-modified proteins (3-chloro-L-tyrosine and 3,5-dichloro-L-tyrosine) were detected in plasma and lung after Cl2-exposure.ConclusionsThe translational model developed in this study replicates key features of humans exposed to Cl2and is suitable to test medical countermeasures. Specific biomarkers of Cl2exposure have been identified in plasma and lung tissue samples.Take home messageWe developed a swine model of chlorine gas-induced acute lung injury that exhibits several features of human acute respiratory distress syndrome. We validated chlorinated fatty acids and protein adducts in plasma and lung samples as forensic biomarkers.
Ontogeny of learning and visual discrimination in zebrafish
Authors: Santacà Maria , Dadda Marco , Valle Luisa Dalla , Fontana Camilla , Gjinaj Gabriela , Bisazza Angelo 
Published: February 2022

SummaryWith the exception of humans, early cognitive development has been thoroughly investigated only in precocial species, well developed at birth and with a broad behavioural and cognitive repertoire. We investigated another highly altricial species, the zebrafish, Danio rerio, whose embryonic development is very rapid: 72 hours. The nervous system of hatchlings is poorly developed, and their cognitive capacities are largely unknown. Larvae trained at 8 days post-fertilisation rapidly learned to associate a visual pattern with a food reward, showing significant performance at 10 days post-fertilisation. We exploited this capacity to study hatchlings’ discrimination learning capacities. Larval zebrafish rapidly and accurately learned colour and shape discriminations. They also discriminated a figure from its mirror image and from its 90°-rotated version, although with lower performance. Our study revealed impressive similarities in learning and visual discrimination capacities between newborn and adult zebrafish despite their enormous differences in brain size and degree of development.
Interaural time difference sensitivity under binaural cochlear implant stimulation persists at high pulse rates up to 900 pps
Authors: Buck Alexa N. , Buchholz Sarah , Schnupp Jan W. , Rosskothen-Kuhl Nicole 
Published: February 2022

AbstractBackgroundSpatial hearing remains one of the major challenges for bilateral cochlear implant (biCI) users, and early deaf patients in particular are often completely insensitive to interaural time differences (ITDs) delivered through biCIs. One popular hypothesis is that this may be due to a lack of early binaural experience. However, we have recently shown that neonatally deafened rats fitted with biCIs in adulthood quickly learn to discriminate ITDs as well as their normal hearing litter mates, and perform an order of magnitude better than human biCI users.MethodsOur unique behaving biCI rat model allows us to investigate other possible limiting factors of prosthetic binaural hearing, such as the effect of stimulus pulse rate and envelope shape. Previous work has indicated that ITD sensitivity may decline substantially at the high pulse rates often used in clinical practice. We therefore measured behavioral ITD thresholds in neonatally deafened, adult implanted biCI rats to pulse trains of 50, 300, 900 and 1800 pulses per second (pps), with either rectangular or Hanning window envelopes.ResultsOur rats exhibited very high sensitivity to ITDs at pulse rates up to 900 pps for both envelope shapes, similar to those in common clinical use. However, ITD sensitivity declined to near zero at 1800 pps, for both Hanning and rectangular windowed pulse trains.ConclusionsCurrent clinical cochlear implant (CI) processors are often set to pulse rates ≥900 pps, but ITD sensitivity in human CI listeners has been reported to decline sharply above ∼300 pps. Our results suggest that the relatively poor ITD sensitivity seen at >300 pps in human CI users may not reflect the hard upper limit of biCI ITD performance in the mammalian auditory pathway. Perhaps with training or better CI strategies good binaural hearing may be achievable at pulse rates high enough to allow good sampling of speech envelopes while delivering usable ITDs.