bluuebunny/crossref_metadata_2025 huggingface dataset:
Unmet Expectations About Material Properties Delay Perceptual Decisions
Authors: Malik Amna , Doerschner Katja , Boyaci Huseyin
Published: August 2022

Based on our expectations about material properties we can implicitly predict an object’s future states, e.g. a wine glass falling down will break when it hits the ground. How these expectations affect relatively low level perceptual decisions, however, has not been systematically studied previously. To seek an answer to this question we conducted a behavioral experiment using animations of various familiar objects (e.g. key, wine glass etc.) freely falling and hitting the ground. During a training session participants first built expectations about the dynamic properties of those objects. Half of the participants (N=28) built expectations consistent with our daily lives (e.g. a key bounces rigidly), whereas the other half learned an anomalous behavior (e.g. a key wobbles). This was followed by experimental sessions, in which expectations were unmet in 20% of the trials. In both training and experimental sessions, participants’ task was to report whether the objects broke or not upon hitting the ground. Critically a specific object always remained intact or broke, only the manner with which it did so differed. For example, a key could wobble or remain rigid, but it never broke. We found that participants’ reaction times were longer when expectations were unmet even when those expectations were anomalous and learned during the training session. Furthermore, we found an interplay between long-term and newly learned expectations, which could be predicted by a Bayesian updating approach. Overall, our results show that expectations about material properties can have an impact on relatively low-level perceptual decision making processes.
Rapid Color Categorization in the Brain Revealed by Frequency-tagging-based EEG
Authors: Sun Mengdan , Gao Xiaoqing
Published: August 2022

The origin of color categories has been debated extensively. Historically, linguistic relativists claim that color categories are shaped by the language we speak and that color terms subsequently affect our perception of color, while universalists postulate that color categories are independent of language and formed based on perceptual mechanisms. A recent hypothesis suggests that the original fine-grained color space in the visual cortex may be transformed into categorical encoding due to top-down modulation. To test the nature of color categorization, our study adopted a sensitive frequency-tagging-based EEG paradigm where the color stimuli were presented sequentially at a fast speed of 10 Hz (SOA: 100 ms) to probe fast, implicit processing of color categories. This SOA was supposed to disrupt top-down feedbacks in visual processing. We showed that EEG responses to cross-category oddball colors at the frequency where the oddball stimuli were presented was significantly larger than the responses to within-category oddball colors. This finding suggested that the brain encodes color categories automatically when top-down feedbacks from frontoparietal areas are blocked. Our study supports the view that the categorical processing of color emerges at the early perceptual stage.
Laminar VASO fMRI in focal hand dystonia patients
Authors: Huber Laurentius (Renzo) , Kassavetis Panagiotis , Gulban Omer Faruk , Hallett Mark , Horovitz Silvina G
Published: August 2022

Focal Hand Dystonia (FHD) is a disabling movement disorder characterized by involuntary movements, cramps and spasms. It is associated with pathological neural microcircuits in the cortical somatosensory system. While invasive preclinical modalities allow researchers to probe specific neural microcircuits of cortical layers and columns, conventional functional magnetic resonance imaging (fMRI) cannot resolve such small neural computational units. In this study, we take advantage of recent developments in ultra-high-field MRI hardware and MR-sequences to capture altered digit representations and laminar processing in FHD patients. We aim to characterize the capability and challenges of layer-specific imaging and analysis tools in resolving laminar and columnar structures in clinical research setups.

We scanned N=4 affected and N=5 unaffected hemispheres at 7T and found consistent results of altered neural microcircuitry in FHD patients: a) In affected hemispheres of FHD patients, we found a breakdown of ordered finger representation in the primary somatosensory cortex, as suggested from previous low-resolution fMRI. b) In affected primary motor cortices of FHD patients, we furthermore found increased fMRI activity in superficial cortico-cortical neural input layers (II/III), compared to relatively weaker activity in the cortico-spinal output layers (Vb/VI).

Overall, we show that layer-fMRI acquisition and analysis tools are applicable to address clinically-driven neuroscience research questions about altered computational mechanisms at the spatial scales that were previously only accessible in animal models. We believe that this study paves the way for easier translation of preclinical work into clinical research in focal hand dystonia and beyond.
TSNAdb v2.0: the updated version of tumor-specific neoantigen database
Authors: Wu Jingcheng , Chen Wenfan , Zhou Yuxuan , Chi Ying , Hua Xiansheng , Wu Jian , Gu Xun , Chen Shuqing , Zhou Zhan
Published: August 2022

Tumor neoantigens have been well-acknowledged as ideal targets for tumor immunotherapy in recent years. With the deepening of research on neoantigen-based tumor immunotherapy, comprehensive neoantigen databases are urgently needed to meet the growing demand for clinical studies. We have built the Tumor-Specific NeoAntigen Database (TSNAdb v1.0) previously, which has attracted wide attention. In this study, we provide an updated version of the Tumor-Specific NeoAntigen Database (TSNAdb v2.0) with several new features including 1) taking stricter criteria for neoantigen identification. 2) providing predicted neoantigens derived from three types of somatic mutations. 3) collecting experimentally validated neoantigens and classifying them according to the evidence. TSNAdb v2.0 is freely available at https://pgx.zju.edu.cn/tsnadb/.
Artificial immune cell,AI-cell, a new tool to predict interferon production by peripheral blood monocytes in response to nucleic acid nanoparticles
Authors: Chandler Morgan , Jain Sankalp , Halman Justin , Hong Enping , Dobrovolskaia Marina A. , Zakharov Alexey V. , Afonin Kirill A.
Published: August 2022

Nucleic acid nanoparticles, or NANPs, are rationally designed to communicate with the human immune system and can offer innovative therapeutic strategies to overcome the limitations of traditional nucleic acid therapies. Each set of NANPs is unique in their architectural parameters and physicochemical properties, which together with the type of delivery vehicles determine the kind and the magnitude of their immune response. Currently, there are no predictive tools that would reliably guide NANPs’ design to the desired immunological outcome, a step crucial for the success of personalized therapies. Through a systematic approach investigating physicochemical and immunological profiles of a comprehensive panel of various NANPs, our research team has developed a computational model based on the transformer architecture able to predict the immune activities of NANPsviaconstruction of so-called artificial immune cell, orAI-cell. TheAI-cellwill aid addressing in timely manner the current critical public health challenges related to overdose and safety criteria of nucleic acid therapies and promote the development of novel biomedical tools.
Cortical dynamics of speech feedback control in non-fluent Primary Progressive Aphasia
Authors: Kothare Hardik , Ranasinghe Kamalini G. , Hinkley Leighton B. , Mizuiri Danielle , Licata Abigail , Lauricella Michael , Honma Susanne , Borghesani Valentina , Dale Corby , Shwe Wendy , Welch Ariane , Miller Zachary , Gorno-Tempini Maria Luisa , Houde John F. , Nagarajan Srikantan S.
Published: August 2022

Primary Progressive Aphasia (PPA) is a clinical syndrome in which patients progressively lose speech and language abilities. The non-fluent variant of PPA (nfvPPA) is characterised by impaired motor speech and agrammatism. To date, no study in nfvPPA patients has either examined speech motor control behaviour or imaged the speech motor control network during vocal production. Here, we did this using a novel structure-function imaging approach integrating magnetoencephalographic imaging of neural oscillations with voxel-based morphometry (VBM). We examined task-induced non-phase-locked neural oscillatory activity during a vocal motor control task, where participants were prompted to phonate the vowel /□/ for ∼2.4s while the pitch of their auditory feedback was shifted either up or down by 100 cents for a period of 400ms mid-utterance. Participants were 18 nfvPPA patients (14 female, mean age = 67.79 ± 8.02 years) and 17 controls (13 female, mean age = 64.81 ± 5.76 years). Patients showed a smaller compensation response to pitch perturbation than controls (p < 0.05). Task-induced neural oscillations across five frequency bands were reconstructed in source space for each subject during pitch feedback perturbation. Patients exhibited reduced task-induced alpha-band (8-12Hz) neural activity unrelated to their atrophy patterns, in the right temporal lobe and the right temporoparietal junction (p < 0.01) from 250ms to 750ms after pitch perturbation onset. Patients also showed increased task-induced beta-band (12-30Hz) activity also unrelated to cortical atrophy in the left dorsal sensorimotor cortex, left premotor cortex and the left supplementary motor area (p < 0.01) from 50ms to 150ms after pitch perturbation onset. Reduced average alpha-band power at the peak voxel in the temporoparietal cluster in the right hemisphere could predict speech motor impairment in patients (β = 3.41, F = 8.31, p = 0.0128) whereas increased average beta-band power at the peak voxel in the left dorsal sensorimotor cluster could not (β = -1.75, F = 1.72, p = 0.2123). Collectively, these results suggest significant disruption in sensorimotor integration during vocal production in nfvPPA patients which occurs unrelated to patterns of atrophy. These findings highlight how multimodal structure-function imaging in PPA enhances our understanding of its pathophysiological sequelae.
The spectral underpinnings of pathogen spread on animal networks
Authors: Fountain-Jones Nicholas M. , Silk Mathew , Appaw Raima Carol , Hamede Rodrigo , Rushmore Julie , VanderWaal Kimberly , Craft Meggan E , Carver Scott , Charleston Michael
Published: August 2022

Predicting what factors promote or protect populations from infectious disease is a fundamental epidemiological challenge. Social networks, where nodes represent hosts and edges represent direct or indirect contacts between them, are important in quantifying these aspects of infectious disease dynamics. However, how network structure and epidemic parameters interact in empirical networks to promote or protect animal populations from infectious disease remains a challenge. Here we draw on advances in spectral graph theory and machine learning to build predictive models of pathogen spread on a large collection of empirical networks from across the animal kingdom. We show that the spectral features of an animal network are powerful predictors of pathogen spread for a variety of hosts and pathogens and can be a valuable proxy for the vulnerability of animal networks to pathogen spread. We validate our findings using interpretable machine learning techniques and provide a flexible web application for animal health practitioners to assess the vulnerability of a particular network to pathogen spread.
Iron accumulation drives fibrosis, senescence, and the senescence-associated secretory phenotype
Authors: Maus Mate , López-Polo Vanessa , Lafarga Miguel , Aguilera Mònica , Lama Eugenia De , Meyer Kathleen , Manonelles Anna , Sola Anna , Martinez Cecilia Lopez , López-Alonso Ines , Hernandez-Gonzales Fernanda , Chaib Selim , Rovira Miguel , Sanchez Mayka , Faner Rosa , Agusti Alvar , Prats Neus , Albaiceta Guillermo , Cruzado Josep M. , Serrano Manuel
Published: August 2022

Fibrogenesis is part of a normal protective response to tissue injury that can become irreversible and progressive, leading to fatal diseases. Senescent cells are a main driver of fibrotic diseases through their secretome, known as senescence-associated secretory phenotype (SASP). However, the mechanisms involved in the conversion of damaged cells into senescent cells remain incompletely understood. Here, we report that multiple types of fibrotic diseases in mice and humans are characterized by the accumulation of iron. We show that vascular and hemolytic injuries, through the release of iron, are efficient in triggering senescence and fibrosis. Interestingly, the accumulation of iron is an intrinsic property of senescent cells that does not require an abnormal surge in extracellular iron. Upon damage, cells initiate an iron accumulation response with abundant ferritin-bound iron within lysosomes and high levels of labile iron, the latter being a main driver of senescence-associated ROS and SASP. Finally, we demonstrate that detection of iron by magnetic resonance imaging (MRI) is a powerful non-invasive method to assess fibrotic burden in the kidneys of mice and patients with renal fibrosis. Our findings establish a central role for iron accumulation in senescence and fibrogenesis.
NEMO- and RelA-dependent NF-κB Signaling Promotes Small Cell Lung Cancer
Authors: Koerner Lioba , Yang Tsun-Po , Schmiel Marcel , Peifer Martin , Buettner Reinhard , Pasparakis Manolis
Published: August 2022

Small cell lung cancer (SCLC) is an aggressive type of lung cancer driven by combined loss of the tumor suppressors RB1 and TP53. SCLC is highly metastatic and despite good initial response to chemotherapy patients usually relapse, resulting in poor survival. Therefore, better understanding of the mechanisms driving SCLC pathogenesis is required to identify new therapeutic targets. Here we identified a critical role of the IKK/NF-κB signaling pathway in SCLC development. Using a relevant mouse model of SCLC, we found that ablation of NEMO/IKKγ, the regulatory subunit of the IKK complex that is essential for activation of canonical NF-κB signaling, strongly delayed the onset and growth of SCLC resulting in considerably prolonged survival. In addition, ablation of the main NF-κB family member p65/RelA also delayed the onset and growth of SCLC and prolonged survival, albeit to a lesser extent than NEMO. Interestingly, constitutive activation of IKK/NF-κB signaling within the tumor cells did not exacerbate the pathogenesis of SCLC, suggesting that endogenous NF-κB levels are sufficient to fully support tumor development. Moreover, TNFR1 deficiency did not affect the development of SCLC, showing that TNF signaling does not play an important role in this tumor type. Taken together, our results revealed that IKK/NF-κB signaling plays an important role in promoting SCLC, identifying the IKK/NF-κB pathway as a promising therapeutic target.
Mapping the Macrostructure and Microstructure of the in vivo Human Hippocampus using Diffusion MRI
Authors: Karat Bradley G. , DeKraker Jordan , Hussain Uzair , Köhler Stefan , Khan Ali R.
Published: August 2022

The hippocampus is classically divided into mesoscopic subfields which contain varying microstructure that contribute to their unique functional roles. It has been challenging to characterize this microstructure with current MR based neuroimaging techniques. In this work, we used diffusion MRI and a novel surface-based approach in the hippocampus which revealed distinct microstructural distributions of neurite density and dispersion, T1w/T2w ratio as a proxy for myelin content, fractional anisotropy, and mean diffusivity. We used the Neurite Orientation Dispersion and Density Imaging (NODDI) model optimized for gray matter diffusivity to characterize neurite density and dispersion. We found that neurite dispersion was highest in the Cornu Ammonis (CA) 1 and subiculum subfields which likely captures the large heterogeneity of tangential and radial fibers, such as the Schaffer collaterals, perforant path, and pyramidal neurons. Neurite density and T1w/T2w were highest in the subiculum and CA3 and lowest in CA1, which may reflect known myeloarchitecture differences between these subfields. Using a simple logistic regression model, we showed that neurite density, dispersion, and T1w/T2w measures provided good separability across the subfields, suggesting that they may be sensitive to the known variability in subfield cyto- and myeloarchitecture. We report macrostructural measures of gyrification, thickness, and curvature that were in line with ex vivo descriptions of hippocampal anatomy. We employed a multivariate orthogonal projective non-negative matrix factorization (OPNNMF) approach to capture co-varying regions of macro- and microstructure across the hippocampus. The clusters were highly variable along the medial-lateral (proximal-distal) direction, likely reflecting known differences in morphology, cytoarchitectonic profiles, and connectivity. Finally, we show that by examining the main direction of diffusion relative to canonical hippocampal axes, we could identify regions with stereotyped microstructural orientations that may map onto specific fiber pathways, such as the Schaffer collaterals, perforant path, fimbria, and alveus. These results highlight the value of combining in vivo diffusion MRI with computational approaches for capturing hippocampal microstructure, which may provide useful features for understanding cognition and for diagnosis of disease states.
12S Gene Metabarcoding with DNA Standard Quantifies Marine Bony Fish Environmental DNA, Identifies Threshold for Reproducible Amplification, and Overcomes Distortion Due to Non-Fish Vertebrate DNA
Authors: Stoeckle Mark Y. , Ausubel Jesse H. , Coogan Michael
Published: August 2022

Single-species PCR assays accurately measure eDNA concentration. Here we test whether multi-species PCR, i.e., metabarcoding, with an internal standard can quantify eDNA of marine bony fish. Replicate amplifications with Riaz 12S gene primers were spiked with known amounts of a non-fish vertebrate DNA standard, indexed separately, and sequenced on an Illumina MiSeq. Fish eDNA copies were calculated by comparing fish and standard reads. Relative reads were directly proportional to relative DNA copies, with average and maximum variance between replicates of about 1.3- and 2.0-fold, respectively. There was an apparent threshold for consistent amplification of about 10 eDNA copies per PCR reaction. The internal DNA standard corrected for distortion of read counts due to non-fish vertebrate DNA. To assess potential amplification bias among species, we compared reads obtained with Riaz 12S primers to those with modified MiFish primers. Our results provide evidence that Riaz 12S gene metabarcoding with an internal DNA standard quantifies marine bony fish eDNA over a range of about 10 to 5,000 copies per reaction, without indication of significant PCR bias among teleost species. In mid-Atlantic coastal samples, eDNA rarity was the main limitation to reproducible detection and quantification, and this was partly overcome by increasing the amount of a DNA sample amplified. Our findings support incorporating a DNA standard in 12S metabarcoding to help quantify eDNA abundance for marine bony fish species.
The managerial role and psychosocial factors of job satisfaction: a cross-sectional study among Wittyfit’s users
Authors: Colin-Chevalier Rémi , Pereira Bruno , Dewavrin Samuel , Cornet Thomas , Żak Marek , Benson Amanda Clare , Dutheil Frédéric
Published: August 2022

Background

Job satisfaction is an emerging indicator for measuring workers’ occupational well-being, however this has been poorly studied in those with managerial roles.

Objective

We aimed to explore job satisfaction in workers and to determine and assess psychosocial factors that may influence this relationship.

Methods

Data from Wittyfit’s users were collected between January 2018 and February 2020. Volunteers anonymously provided socio-demographic data and responses to questionnaires about their levels of job satisfaction and psychosocial feelings (ambiance, meaning, organization, recognition, values, work-life balance).

Results

10,484 employees (40.9% of women) and 836 managers (33.9% of women), i.e. 11,320 workers with median age of 45 years and seniority of median 10 years of service, were included in the study. Job satisfaction of workers was higher in managers than employees (mean ± SD 68.1 ± 20.4 vs 57.8 ± 24.2, p < .001), as were their feelings about ambiance (71.2 ± 20.9 vs 66.1 ± 24.2), meaning (66.9 ± 21.8 vs 56.1 ± 23.1), organization (55.3 ± 23.6 vs 46.6 ± 24.6), recognition (62.8 ± 23.9 vs 48.3 ± 26.7) and values (66.3 ± 21.7 vs 56.5 ± 23.1) (p < .001). There was no difference in work-life balance (58.1 ± 23.9 vs 59.2 ± 23.4, p = 0.2). All psychosocial factors had an impact on job satisfaction for both managers and employees (p < .001). High job satisfaction was more prevalent in workers who were managers than in employees (84.6 vs 68.8%, p < .001). Even though the managerial position was the most influential factor of job satisfaction (OR = 2.65, 95% CI 2.18 to 3.23, p < .001), other socio-demographic variables such as age (0.87, 0.79 to 0.95, p = 0.002) and seniority (0.71, 0.65 to 0.79, p < .001) also had an influence, although three times less.

Conclusions

Managers seem to have higher job satisfaction and psychosocial feelings about their work than employees. Psychosocial factors, many which are modifiable, as well as socio-demographic factors such as age and seniority, may influence job satisfaction among workers.

Trial registration

Clinicaltrials.gov: NCT02596737.
Contribution of the eye and ofopn4xafunction to circadian photoentrainment in the diurnal zebrafish
Authors: Chaigne Clair , Sapède Dora , Cousin Xavier , Sanchou Laurent , Blader Patrick , Cau Elise
Published: August 2022

The eye is instrumental for controlling circadian rhythms in mice and human. Here, we address the conservation of this function in the zebrafish, a diurnal vertebrate. Using lakritz (lak) mutant larvae, which lack retinal ganglion cells (RGCs), we show that while a functional eye contributes to masking, it is largely dispensable for the establishment of circadian rhythms of locomotor activity. Furthermore, the eye is dispensable for the induction of a phase delay following a pulse of white light at CT 16 but contributes to the induction of a phase advance upon a pulse of white light at CT21. Melanopsin photopigments are important mediators of photoentrainment, as shown in nocturnal mammals. One of the zebrafish melanopsin genes,opn4xa, is expressed in RGCs but also in photosensitive projection neurons in the pineal gland. Pinealopn4xa+ projection neurons function in a LIGHT ON manner in contrast to other projection neurons which function in a LIGHT OFF mode. We generated anopn4xamutant in which the pineal LIGHT ON response is impaired. This mutation has no effect on masking and circadian rhythms of locomotor activity, or for the induction of phase shifts, but slightly modifies period length when larvae are subjected to constant light. Finally, analysis ofopn4xa;lakdouble mutant larvae did not reveal redundancy between the function of the eye andopn4xain the pineal for the control of phase shifts after light pulses. Our results support the idea that the eye is not the sole mediator of light influences on circadian rhythms of locomotor activity and highlight differences in the circadian system and photoentrainment of behaviour between different animal models.

Author summary

Experiments performed in mice have established a crucial role for the eye in general and melanopsin expressing cells in particular in the control of circadian rhythms most notably during photoentrainment, by which circadian rhythms adapt to a changing light environment. In marked contrast to this, we show that in zebrafish the eye and photosensitivity dependent on one of the melanopsin genes,opn4xa, which is expressed in both the eye and the pineal gland, are largely dispensable for correct circadian rhythms. These results provide insight that the light sensors orchestrating circadian rhythms of locomotor activity are different between animal models supporting that vertebrates might employ different molecular/cellular circuits for photoentrainment of behaviour depending on their phylogeny and/or temporal niche.
Causal contributions to sensory-based decision-making by cell-type specific circuits in the tail striatum
Authors: Cui Lele , Tang Shunhang , Zhao Kai , Pan Jingwei , Zhang Zhaoran , Si Bailu , Xu Ning-long
Published: August 2022

The striatum comprises distinct types of neurons giving rise to the direct and indirect basal ganglia pathways and local circuits. A large amount of work has been focusing on cell-type specific striatal circuits in the context of movement control, proposing several models on their functional roles. But it remains to be elucidated how the cell-type specific striatal circuits contribute to decision-making behavior and whether the existing models apply. Here, we investigate the causal roles of the cell-type specific circuits in the posterior tail of the dorsal striatum (TS) of mice in an auditory-guided decision-making behavior. Transient unilateral activation of the direct- or indirect-pathway striatal spiny projection neurons (dSPNs or iSPNs) both biased decisions in opposite directions. These effects, however, were not due to a direct influence on movement, but was specific to the decision period preceding action execution. Optogenetic inactivation of dSPNs and iSPNs revealed their opposing causal contributions to decisions. At the local circuit level, simutaneous optical recording and manipulation of dSPNs and iSPNs revealed their antagnizing interactions. Inactivation of PV interneurons, a common inhibitory input to both dSPNs and iSPNs, facilitated contraversive choices, supporting a causal contribution of coordinated striatal circuits. Using a neural circuit model, we further demonstrated the computational implemenation of the causal circuit mechanism. Our results indicate that while the causal roles of the cell-type specific striatal circuits in decision-making largely agree with classic models in movement control, they show decision task-related specificity involving local circuit coordination.
Tree and shrub richness modify subtropical tree productivity by modulating the diversity and community composition of soil bacteria and archaea
Authors: Tao Siqi , Veen G. F. (Ciska) , Yu Tianhe , Zhang Naili , Qu Laiye
Published: August 2022

Background

Declines in plant biodiversity often have negative consequences for plant community productivity, and it becomes increasingly acknowledged that this may be driven by shifts in soil microbial community composition. These relationships have been well-established in grasslands, and few studies also indicate that fungi play a role in driving tree diversity-productivity relationships in forests. However, the role of bacteria and archaea, which are also highly abundant in forest soils and perform pivotal ecosystem functions, has been largely overlooked. Here, we investigated how tree and shrub richness affects stand-level tree productivity via modulating bacterial and archaeal community diversity and composition. We used a landscape-scale, subtropical tree biodiversity experiment (BEF-China) where tree (1, 2 or 4 species) and shrub richness (0, 2, 4, 8 species) were modified.

Results

Our results showed that tree and shrub species richness affected bacterial diversity, community composition, and co-occurrence networks, but such effects were marginal for archaea. Both tree and shrub species richness increased stand-level tree productivity by modulating soil microbial community composition, with the effects being mediated via increases in soil C:N ratios.

Conclusions

Our findings imply the importance of bacterial and archaeal communities in driving the relationship between plant diversity and productivity in subtropical forests and highlight that we may require better a understanding of prokaryotic communities in forest soils.
Catalyst: Fast and flexible modeling of reaction networks
Authors: Loman Torkel E. , Ma Yingbo , Ilin Vasily , Gowda Shashi , Korsbo Niklas , Yewale Nikhil , Rackauckas Chris , Isaacson Samuel A.
Published: August 2022

We introduce Catalyst.jl, a flexible and feature-filled Julia library for modeling and high-performance simulation of chemical reaction networks (CRNs). Catalyst supports simulating stochastic chemical kinetics (jump process), chemical Langevin equation (stochastic differential equation), and reaction rate equation (ordinary differential equation) representations for CRNs. Through comprehensive benchmarks, we demonstrate that Catalyst simulation runtimes are often one to two orders of magnitude faster than other popular tools. More broadly, Catalyst acts as both a domain-specific language and an intermediate representation for symbolically encoding CRN models as Julia-native objects. This enables a pipeline of symbolically specifying, analyzing, and modifying CRNs; converting Catalyst models to symbolic representations of concrete mathematical models; and generating compiled code for numerical solvers. Leveraging ModelingToolkit.jl and Symbolics.jl, Catalyst models can be analyzed, simplified, and compiled into optimized representations for use in numerical solvers. Finally, we demonstrate Catalyst’s broad extensibility and composability by highlighting how it can compose with a variety of Julia libraries, and how existing open-source biological modeling projects have extended its intermediate representation.
Differential Analysis of Stromal-Epithelial Interactions between In Situ and Invasive Breast Cancer using Gene Expression Profiling
Authors: Officer Adam , Dempsey Andre M. , Murrow Lyndsay M. , Gartner Zev , Tamayo Pablo , Yau Christina , Harismendy Olivier
Published: August 2022

Background

Changes in microenvironment cell-cell interactions (CCI) during the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) are poorly understood. Gene expression studies are confounded by cellular heterogeneity and few separate stromal and epithelial contributions, resulting in a lack of reliable prognostic biomarker to guide treatment decisions.

Methods

The gene expression of 293 microdissected regions from DCIS (92 epithelial, 31 stromal) and IDC (78 epithelial, 30 stromal) cases was aggregated from 6 datasets. Expression signatures of 6 cell lineages extracted from normal breast single-cell profiling were used to correct for differences in cell abundance. Subtype-specific functional differences between DCIS and IDC were measured for each region type using Gene Set Enrichment Analysis (GSEA). DCIS-IDC stromal-epithelial interactions were compared using the expression product of 139 ligand-receptor (LR) pairs permuting the DCIS-IDC labels to assess significance.

Results

Variation in cell-lineage abundance separated epithelial regions into 4 clusters, including one enriched for DCIS (Myoepi-Enriched) and two for IDC (Infiltrated, Vascularized). GSEA on cell lineage normalized expression data identified subtype-independent changes in epithelial regions (induction of Extracellular Matrix maintenance genes, reduction of Tp53 signaling in IDC), as well as subtype-specific changes (proliferation in ER- and Her2-IDC, reduction in Nucleotide Excision Repair in ER+ IDC). In the stroma, Notch and Rho-GTPase signaling were induced in IDC irrespective of subtype. The stromal-epithelial interaction level of 6 and 4 LR pairs were significantly enriched in DCIS and IDC, respectively. Five of the 6 DCIS-enriched LR pairs involved ephrin interactions, with interaction level progressively decreasing from normal to DCIS to IDC. In contrast, 2 IDC-enriched LR pairs involved T-cell activity likely regulating Treg proliferation (CD28-CD86) or T and NK cells stimulation (CD226-PVR). Notably, the bulk expression product of one identified LR pair (EPHB4-EFNB1) was associated with poor survival in IDC (HR=1.47, p=0.04) suggesting that early remodeling of this stromal-epithelial interaction may have long-lasting impact on disease severity.

Conclusions

The observed changes in cell states and stromal-epithelial interactions, beyond those driven by difference in cell abundance, may lead to new biomarkers for prognosis and targets for secondary prevention.
Neural patterns differentiate traumatic from sad autobiographical memories in PTSD
Authors: Perl Ofer , Duek Or , Kulkarni Kaustubh R. , Kelmendi Ben , Amen Shelley , Gordon Charles , Krystal John H. , Levy Ifat , Harpaz-Rotem Ilan , Schiller Daniela
Published: August 2022

For people with post-traumatic stress disorder (PTSD), recalling traumatic memories often displays as intrusions that differ profoundly from processing of ‘regular’ negative memories. These mnemonic features fueled theories speculating a qualitative divergence in cognitive state linked with traumatic memories. Yet to date, little empirical evidence supports this view. Here, we examined neural activity of PTSD patients who were listening to narratives depicting their own memories. An inter-subject representational similarity analysis of cross-subject semantic content and neural patterns revealed a differentiation in hippocampal representation by narrative type: Semantically similar sad autobiographical memories elicited similar neural representations across participants. By contrast, within the same individuals, semantically thematically similar trauma memories were not represented similarly. Furthermore, we were able to decode memory type from hippocampal multivoxel patterns. Finally, individual symptom severity modulated semantic representation of the traumatic narratives in the posterior cingulate cortex. Taken together, these findings suggest that traumatic memories are a qualitatively divergent cognitive entity.
Functional morphological innovation corresponds to shifting lines of genetic least resistance
Authors: Parins-Fukuchi C. Tomomi , Saulsbury James G.
Published: August 2022

Phenotypic traits are often constrained in their evolution by the genetic and developmental map underlying them. However, the extent to which these constraints themselves evolve has not been well-characterized. Traits that are integrated are generally thought to be constrained in their ability to evolve because their shared developmental and genetic architecture causes any change in one to be mirrored in the other. Nevertheless, it is not yet clear whether correlations can constrain major episodes of phenotypic diversification over longer timescales. We reconstruct patterns in integration within nine primate lineages and model the evolution of the resulting modules in a phylogenetic context. We find that patterns in integration are generally evolvable across lineages, with apes displaying particular lability in the composition of morphological modules. This increased turnover in module composition corresponds to both divergent evolution of skeletal shape and the formation of novel complexes of locomotor behaviors and postures. While integration may play a role in constraining evolutionary innovation, its effects are dynamic, shifting as the structure of integration itself evolves during episodes of exceptional ecomorphological diversification.
Known phyla dominate the RNA virome in Tara Oceans data, not new phyla as claimed
Authors: Edgar Robert C.
Published: August 2022

The Tara Oceans project claimed to identify five new RNA virus phyla, two of which “are dominant in the oceans”. However, their own assignments classify 28,353 of their putative RdRp-containing contigs to known phyla but only 886 (2.8%) to the five claimed new phyla combined. I mapped their reads to their contigs, finding that known phyla also account for a large majority (93.8%) of reads. I show that 510 of their putative viral contigs contain cellular proteins and further that predicted polymerase structures for their claimed phyla have incomplete and malformed palm domains, contradicting viral polymerase function and calling into question whether their putative polymerase sequences are derived from viruses.
Decoding Subject’s Own Name in the Primary Auditory Cortex
Authors: Wu Hang , Wang Dong , Liu Yueyao , Xie Musi , Zhou Liwei , Wang Yiwen , Cao Jin , Huang Yujuan , Qiu Mincong , Qin Pengmin
Published: August 2022

Current studies have shown that perception of subject’s own name (SON) involves multiple multimodal brain regions, while activities in unimodal sensory regions (i.e., primary auditory cortex) and their interaction with multimodal regions during the self-processing remain unclear. To answer this, we combined multivariate pattern analysis and dynamic causal modelling analysis to explore the regional activation pattern and inter-region effective connection during the perception of SON. We found that SON and other names could be decoded from the activation pattern in the primary auditory cortex. In addition, we found an excitatory effect of SON on connections from the anterior insula/inferior frontal gyrus to the primary auditory cortex, and to the temporal parietal junction. Our findings extended the current knowledge of self-processing by showing that primary auditory cortex could discriminate SON from other names. Furthermore, our findings highlighted the importance of influence of the insula on the primary auditory cortex during self-processing.
Exploring the role of abiotic factors on the seedling recruitment of three plant species in the Colombian Amazon
Authors: Palma Ana C , Stevenson Pablo R.
Published: August 2022

Our work seeks to explore certain abiotic factors that could affect seedling recruitment in neotropical moist forest. We selected three plant species (Caraipa sp., Tachigali sp., and Dicranostyles sp.) and investigated the role of nutrients, proximity to the parent tree, competition (intra-and inter-specific) and light availability on seedling growth and survival. We planted seedlings in the forest understory and in a shade house and applied four different treatments to evaluate the role of abiotic factors on recruitment. Our results show that the studied species were not negatively influenced by distance-dependent processes or by competition during the study period (6-7 mo.). We found that light availability was the most important factor determining seedlings’ early performance. The studied species showed distinct responses to the different treatments; therefore, it is hard to draw general conclusions about which factors might be affecting seedling recruitment and promoting the high plant diversity of tropical moist forest.
Large vesicle extrusions fromC. elegansneurons are consumed and stimulated by glial-like phagocytosis activity of the neighboring cell
Authors: Wang Yu , Arnold Meghan Lee , Smart Anna Joelle , Wang Guoqiang , Androwski Rebecca J. , Morera Andres , Nguyen Ken C. , Schweinsberg Peter J. , Bai Ge , Cooper Jason , Hall David H. , Driscoll Monica , Grant Barth D.
Published: August 2022

C. elegansneurons under stress can produce giant vesicles, several microns in diameter, called exophers. Current models suggest that exophers are neuroprotective, providing a mechanism for stressed neurons to eject toxic protein aggregates and organelles. However, little is known of the fate of the exopher once it leaves the neuron. We found that exophers produced by mechanosensory neurons inC. elegansare engulfed by surrounding hypodermal skin cells and are then broken up into numerous smaller vesicles that acquire hypodermal phagosome maturation markers, with vesicular contents gradually degraded by hypodermal lysosomes. Consistent with the hypodermis acting as an exopher phagocyte, we found that exopher removal requires hypodermal actin and Arp2/3, and the hypodermal plasma membrane adjacent to newly formed exophers accumulates dynamic F-actin during budding. Efficient fission of engulfed exopher-phagosomes to produce smaller vesicles and degrade their contents requires phagosome maturation factors SAND-1/Mon1, GTPase RAB-35, the CNT-1 ARF-GAP, and microtubule motor associated GTPase ARL-8, suggesting a close coupling of phagosome fission and phagosome maturation. Lysosome activity was required to degrade exopher contents in the hypodermis but not for exopher-phagosome resolution into smaller vesicles. Importantly, we found that GTPase ARF-6 and effector SEC-10/Exocyst activity in the hypodermis, along with the CED-1 phagocytic receptor, is required for efficient production of exophers by the neuron. Our results indicate that the neuron requires specific interaction with the phagocyte for an efficient exopher response, a mechanistic feature potentially conserved with mammalian exophergenesis, and similar to neuronal pruning by phagocytic glia that influences neurodegenerative disease.
Transcranial electrical stimulation modulates emotional experience and metabolites in the prefrontal cortex in a donation task
Authors: Mugnol-Ugarte L , Bortolini T , Mikkelsen M , Monteiro M Carneiro , Andorinho AC , Bramatti Ivanei E. , Melo B , Hoefle S , Meireles F , Yao Bo , Moll J , Pobric G
Published: August 2022

In this study we investigated whether transcranial Direct Current Stimulation (tDCS) applied to two prefrontal cortex regions, the ventromedial prefrontal cortex (vmPFC, anode) and right dorsolateral prefrontal cortex (DLPFC, cathode) can be used to induce changes in self-reported emotions and modulate metabolite concentrations under both electrodes. We employed in vivo quantitative MR Spectroscopy (MRS) in healthy adult participants and quantified the changes in GABA and Glx complex (Glutamate and Glutamine) before and after five sessions of tDCS stimulation. tDCS was delivered at 2mA intensity for 20 minutes for the active group and 1 minute for the sham group. tDCS was applied over five days while participants were engaged in a charitable donation task, known to engage the reward network. We observed increased levels of GABA in vmPFC, but not in DLPFC. Glx levels were decreased in both vmPFC and DLPFC. We found that self-reported happiness increased significantly over time only in the active group. There was a decrease in self-reported guiltiness in both active and sham groups. Altogether, the results indicate that self-reported emotions can be modulated by prefrontal stimulation. This may be because the changes in GABA and Glx concentrations following repeated stimulation induce remote changes in the reward network through interactions with other metabolites, previously thought to be unreachable with noninvasive stimulation techniques.
Learning Optimal White Matter Tract Representations from Tractography using a Deep Generative Model for Population Analyses
Authors: Feng Yixue , Chandio Bramsh Q. , Chattopadhyay Tamoghna , Thomopoulos Sophia I. , Owens-Walton Conor , Jahanshad Neda , Garyfallidis Eleftherios , Thompson Paul M.
Published: August 2022

Whole brain tractography is commonly used to study the brain’s white matter fiber pathways, but the large number of streamlines generated - up to one million per brain - can be challenging for large-scale population studies. We propose a robust dimensionality reduction framework for tractography, using a Convolutional Variational Autoencoder (ConvVAE) to learn low-dimensional embeddings from white matter bundles. The resulting embeddings can be used to facilitate downstream tasks such as outlier and abnormality detection, and mapping of disease effects on white matter tracts in individuals or groups. We design experiments to evaluate how well embeddings of different dimensions preserve distances from the original high-dimensional dataset, using distance correlation methods. We find that streamline distances and inter-bundle distances are well preserved in the latent space, with a 6-dimensional optimal embedding space. The generative ConvVAE model allows fast inference on new data, and the smooth latent space enables meaningful decodings that can be used for downstream tasks. We demonstrate the use of a ConvVAE model trained on control subjects’ data to detect structural anomalies in white matter tracts in patients with Alzheimer’s disease (AD). Using ConvVAEs to facilitate population analyses, we identified 6 tracts with statistically significant differences between AD and controls after controlling for age and sex effect, visualizing specific locations along the tracts with high anomalies despite large inter-subject variations in fiber bundle geometry.
Spatial mapping of human lung tissue reveals granuloma diversity and histopathological superstructure in tuberculosis
Authors: Sawyer Andrew , Patrick Ellis , Edwards Jarem , Wilmott James S , Fielder Timothy , Yang Qianting , Barber Daniel L , Ernst Joel D , Britton Warwick J , Palendira Umaimainthan , Chen Xinchun , Feng Carl G
Published: August 2022

The histopathological hallmark of tuberculosis (TB) is the formation of immune cell enriched aggregates called granulomas, but the scope of granuloma heterogeneity in human TB is unknown. By spatially mapping individual immune cells across large regions of TB lung tissue, we report that in addition to necrotizing granulomas, the human TB lung contains abundant non-necrotizing leukocyte aggregates surrounding areas of necrotizing tissue. These cellular lesions were more diverse in composition than necrotizing lesions and could be stratified into four general classes based on cellular composition and spatial distribution of B cells and macrophages, indicating there are foci of distinct immune reactions adjacent to necrotizing granulomas. We further show that the specific cellular composition of non-necrotizing structures correlates with their proximity to necrotizing lesions. Together, our study shows that during tuberculosis diseased lung tissue develops a histopathological superstructure comprising at least four different types of non-necrotizing cellular aggregates organized as satellites of necrotizing granulomas.
Origin, Prospective Identification, and Function of Circulating Endothelial Colony Forming Cells in Mouse and Human
Authors: Lin Yang , Banno Kimihiko , Gil Chang-Hyun , Myslinski Jered , Hato Takashi , Shelley William C. , Gao Hongyu , Xuei Xiaoling , Liu Yunlong , Basile David P. , Yoshimoto Momoko , Prasain Nutan , Tarnawsky Stefan P. , Adams Ralf H. , Naruse Katsuhiko , Yoshida Junko , Murphy Michael P. , Horie Kyoji , Yoder Mervin C.
Published: August 2022

Most circulating endothelial cells are apoptotic, but rare circulating endothelial colony forming cells (C-ECFCs) with proliferative and vasculogenic activity can be cultured; the origin and naïve function of these C-ECFCs remains obscure. Herein, detailed lineage tracing reveals murine C-ECFCs emerge in the early postnatal period, display high vasculogenic potential, with enriched frequency of clonal proliferative cells compared to tissue-resident ECFCs, and are not committed to or derived from the bone marrow hematopoietic system but from tissue-resident ECFCs. In human subjects, C-ECFCs are present in the CD34bright cord blood mononuclear subset, possess proliferative potential and in vivo vasculogenic function in a naïve or cultured state, and display a single cell transcriptome sharing some umbilical venous endothelial cell features like, higher Protein C Receptor and extracellular matrix gene expression. This study provides an advance for the field by identifying the origin, naïve function, and antigens to prospectively isolate C-ECFCs for translational studies.