bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiological surveillance of respiratory pathogens in wastewater in Belgium
Authors: Rector Annabel , Bloemen Mandy , Thijssen Marijn , Pussig Bram , Beuselinck Kurt , Van Ranst Marc , Wollants Elke
Published: October 2022

Background

Detailed information on the circulation of respiratory viruses in the community is crucial to gain better understanding of the burden of respiratory infections on society.

Methods

By using an in-house respiratory panel for simultaneous detection of 29 respiratory pathogens (22 viruses and 7 bacteria/fungi), we explored the possibility to use wastewater sampling to monitor the circulation of respiratory pathogens at population level.

Results

We were able to detect all respiratory viruses included in the panel (influenza A, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), parainfluenza viruses (PIV) 1-4, adenovirus (Adv), human bocavirus (HBoV), enterovirus/rhinovirus (EV/RV), enterovirus D68 (EV-D68), parechovirus (HPeV), human coronaviruses (HCoV)-NL63, -229E, -OC43, -HKU-1 and -SARS, cytomegalovirus (CMV) and herpes simplex virus (HSV)-1 and -2), except for influenza B and HCoV MERS which were not circulating in Belgium during the two year study period. An upsurge of EV-D68 infections in Europe in September 2021 was clearly reflected in the wastewater samples. For the viruses where epidemiological data on virus circulation in Belgium were available, these matched the wastewater data. The wastewater pretreatment that was used, optimized for viral enrichment, was as such not suited for the surveillance of bacteria and fungi.

Conclusions

Community circulation levels of respiratory viruses were well reflected in wastewater samples, indicating that wastewater-based epidemiology can be a valuable tool in the epidemiology and management of respiratory infections.
Associations Between Resting State Functional Brain Connectivity and Childhood Anhedonia: A Reproduction and Replication Study
Authors: Zhou Yi , Pat Narun , Neale Michael C.
Published: October 2022

Background

Previously, a study using a sample of the Adolescent Brain Cognitive Development (ABCD)® study from the earlier 1.0 release found differences in several resting state functional MRI (rsfMRI) brain connectivity measures associated with children reporting anhedonia. Here, we aim to reproduce, replicate, and extend the previous findings using data from the later ABCD study 4.0 release, which includes a significantly larger sample.

Methods

To reproduce and replicate the previous authors’ findings, we analyzed data from the ABCD 1.0 release (n = 2437), in an independent subsample from the newer ABCD 4.0 release (n = 6456), and in the full ABCD 4.0 release sample (n = 8866). Additionally, we assessed whether using a multiple linear regression approach could improve replicability by controlling for the effects of comorbid psychiatric conditions and socio-demographic covariates.

Results

We could only replicate the significant association between anhedonia and theWithin Cingulo-Opercular network connectivitymeasure in an independent subsample of the ABCD 4.0 data release. When using the larger full ABCD 4.0 sample, six out of the eleven previously reported associations remained significant. Accounting for socio-demographic covariates and comorbid conditions using multiple linear regression did not improve replicability but allowed for the identification of specific and independent effects of anhedonia on 16 rsfMRI connectivity measures in the full ABCD 4.0 release sample.

Conclusion

Replication of previous findings were limited. A multiple linear regression approach helped resolve the specificity of rsfMRI connectivity associations with anhedonia.
Extending the audiogram with loudness growth: revealing complementarity in bimodal aiding
Authors: Lambriks Lars , van Hoof Marc , George Erwin , Devocht Elke
Published: October 2022

Introduction

Clinically, the audiogram is the most commonly used measure when evaluating hearing loss and fitting hearing aids. As an extension, we present the loudness audiogram, which does not only show auditory thresholds but also visualises the full course of loudness perception.

Methods

In a group of 15 bimodal users, loudness growth was measured with the cochlear implant and hearing aid separately using a loudness scaling procedure. Loudness growth curves were constructed, using a novel loudness function, for each modality and then integrated in a graph plotting frequency, stimulus intensity level, and loudness perception. Bimodal benefit, defined as the difference between wearing a cochlear implant and hearing aid together versus wearing only a cochlear implant, was assessed for multiple speech outcomes.

Results

Loudness growth was related to bimodal benefit for speech understanding in noise and to some aspects of speech quality. No correlations between loudness and speech in quiet were found. Patients who had predominantly unequal loudness input from the hearing aid, gained more bimodal benefit for speech understanding in noise compared to those patients whose hearing aid provided mainly equivalent input.

Discussion

Fitting the cochlear implant and a contralateral hearing aid to create equal loudness at all frequencies may not always be beneficial for speech understanding.
Determination of insulin secretion from stem cell-derived islet organoids with liquid chromatography-tandem mass spectrometry
Authors: Olsen Christine , Wang Chencheng , Abadpour Shadab , Lundanes Elsa , Hansen Audun Skau , Skottvoll Frøydis Sved , Scholz Hanne , Wilson Steven Ray
Published: October 2022

Organoids are laboratory-grown 3D organ models, mimicking human organs for e.g. drug development and personalized therapy. Islet organoids (typically 100-200 μm), which can be grown from the patient’s own cells, are emerging as prototypes for transplantation-based therapy of diabetes. Selective methods for quantifying insulin production from islet organoids are needed, but sensitivity and carry-over have been major bottlenecks in previous efforts. We have developed a reverse phase liquid chromatography-tandem mass spectrometry (RPLC-MS/MS) method for studying the insulin secretion of islet organoids. In contrast to our previous attempts using nano-scale LC columns, conventional 2.1 mm inner diameter LC column (combined with triple quadrupole mass spectrometry) was well suited for sensitive and selective measurements of insulin secreted from islet organoids with low microliter-scale samples. Insulin is highly prone to carry-over, so standard tubings and injector parts were replaced with shielded fused silica nanoViper™ connectors. As samples were expected to be very limited, an extended Box-Behnken experimental design for the MS settings was conducted to maximize performance. The finale method has excellent sensitivity, accuracy and precision (limit of detection: ≤ 0.2 pg/μL, relative error: ≤ ±10%, relative standard deviation: < 10%), and was well suited for measuring 20 μL amounts of Krebs buffer containing insulin secreted from islet organoids.
Localized APP pathology in the hippocampus is sufficient to result in progressive disorganization of the timing of neuronal firing patterns
Authors: Viana da Silva Silvia , Haberl Matthias G. , Gaur Kshitij , Patel Rina , Narayan Gautam , Ledakis Max , Fu Maylin L. , Koo Edward H. , Leutgeb Jill K. , Leutgeb Stefan
Published: October 2022

Deficits in spatial navigation are among the early symptoms in Alzheimer’s disease patients, consistent with the hippocampal formation as the site for spatial computations and disease onset. Although the correspondence between the early symptoms and brain regions that are affected early in the disease has been recognized, it is not clear whether progressive cognitive decline is solely caused by a spreading pathology or whether a focal pathology can by itself cause aberrant neuronal activity in a larger network. These possibilities cannot be distinguished in standard disease models which broadly express APP across brain regions. We therefore generated a mouse model in which the expression of mutant human APP was limited to hippocampal CA3 cells (CA3-APP mice). We first asked whether the limited pathology in CA3 can result in memory deficits and found impaired performance of CA3-APP mice in a hippocampus-dependent memory task. By then recording in the CA1 region, we asked to what extent neuronal activity patterns emerged in a brain region which received projections from APP-expressing CA3 cells, but did itself not show any primary pathology. While the spatial firing patterns of CA1 cells were preserved, we observed a reduced theta oscillation frequency in the local field potential and in a subpopulation of principal cells in CA1. Furthermore, CA1 interneurons showed decreased theta oscillation frequencies, and this effect was even more pronounced in CA3 interneurons, which also do not directly express APP. Pathology that is highly localized and limited to presynaptic cells is thus sufficient to cause aberrant firing patterns in postsynaptic neuronal networks, which indicates that disease progression is not only from a spreading molecular pathology but also mediated by progressive physiological dysfunction.
Fast-exchanging spirocyclic rhodamine probes for aptamer-based super-resolution RNA imaging
Authors: Englert Daniel , Burger Eva-Maria , Lackner Jens , Lampe Marko , Bühler Bastian , Grün Franziska , Schokolowski Janin , Nienhaus G. Ulrich , Jäschke Andres , Sunbul Murat
Published: October 2022

Live-cell RNA imaging with high spatial and temporal resolution remains a major challenge. Here we report the development of RhoBAST:SpyRho, a fluorescent light-up aptamer (FLAP) system ideally suited for visualizing RNAs in live or fixed cells with various advanced fluorescence microscopy modalities. Overcoming problems associated with low cell permeability, brightness, fluorogenicity, and signal-to-background ratio of previous fluorophores, we designed a novel probe, SpyRho (Spirocyclic Rhodamine), which tightly binds to the RhoBAST aptamer. High brightness and fluorogenicity is achieved by shifting the equilibrium between spirolactam and quinoid. With its high affinity and fast ligand exchange, RhoBAST:SpyRho is a superb system for both super-resolution SMLM and STED imaging. Its excellent performance in SMLM and the first reported super-resolved STED images of specifically labeled RNA in live mammalian cells represent significant advances over other FLAPs. The versatility of RhoBAST:SpyRho is further demonstrated by imaging endogenous chromosomal loci and proteins.
Identification of the area sampled by traps: a modelling study with tsetse
Authors: Vale Glyn A , Hargrove John W , Torr Steve J
Published: October 2022

Background

Sampling with traps provides the most common means of investigating the abundance, composition and condition of tsetse populations. It is thus important to know the size of the area from which the samples originate, but that topic is poorly understood.

Methods and principal findings

The topic was clarified with the aid of a simple deterministic model of the mobility, births and deaths of tsetse. The model assessed how the sampled area changed according to variations in the numbers, arrangement and catching efficiency of traps deployed for different periods in a large block of homogeneous habitat subject to different levels of fly mortality. The greatest impacts on the size of the sampled area are produced by the flies’ mean daily step length and the duration of trapping. There is little effect of trap type. The daily death rate of adult flies is unimportant unless tsetse control measures increase the mortality several times above the low natural rates. Formulae are suggested for predicting the probability that any given captured fly will have originated from various areas around the trap.

Conclusions

Formulae for predicting the probability that any given captured fly originated from various areas around the trap are produced. Using a mean daily step length (d)of 395m, typical of a savannah species of tsetse, then any fly caught by a single trap in a 5-day trapping period could be regarded, with roughly 95% confidence, as originating from within a distance of 1.3km of the trap, that is from an area of 5.5km2.

Authors Summary

We produced a simple, deterministic model to highlight important principles in the neglected matter of the probability that any trapped tsetse will have originated from various sizes of area around the trapping site. The modelling was kept simple by envisaging the use of just one trap, or a group of only five traps, evenly spaced inside a circular area within a large block of homogeneous habitat and operated for no more than 30 days. In deriving formulae for the sampled area, we found it appropriate to consider only the flies’ mean daily step length, and the number of days duration of trapping. The type of trap employed was unimportant. The daily mortality of the adult tsetse population had little effect unless the death rates imposed by control measures were several times greater than the natural rates.
Analysis of an Indian colorectal cancer faecal microbiome collection demonstrates universal colorectal cancer-associated patterns, but closest correlation with other Indian cohorts
Authors: Bose Mayilvahanan , Wood Henry M , Young Caroline ,   International CRC Microbiome Network (AMS/CRUK), Quirke Philip , Seshadri Ramakrishan Ayloor
Published: October 2022

It is increasingly being recognised that changes in the gut microbiome have either a causative or associative relationship with colorectal cancer (CRC). However, most of this research has been carried out in a small number of developed countries with high CRC incidence. It is unknown if lower incidence countries such as India have similar microbial associations.

Having previously established protocols to facilitate microbiome research in regions with developing research infrastructure, we have now collected and sequenced microbial samples from a larger cohort study of 46 Indian CRC patients and 43 healthy volunteers. When comparing to previous global collections, these samples resemble other Asian samples, with relatively high levels ofPrevotella. Predicting cancer status between cohorts shows good concordance. When compared to a previous collection of Indian CRC patients, there was similar concordance, despite different sequencing technologies between cohorts. These results show that there does seem to be a global CRC microbiome, and that some inference between studies is reasonable. However, we also demonstrate that there is definite regional variation, with more similarities between location-matched comparisons. This emphasises the importance of developing protocols and advancing infrastructure to allow as many countries as possible to contribute to microbiome studies of their own populations.

Importance

Colorectal cancer is increasing in many countries, thought to be partly due to the interaction between gut bacteria and changing diets. While it is known that populations in different parts of the world have very different gut microbiomes, the study of their role in colorectal cancer is almost exclusively based in the USA and Europe. We have previously shown that there is overlap between the colorectal cancer microbiome in multiple different countries, establishing robust protocols in the process. Here we expand that into a new Indian cohort. We show that while there are similarities between countries, by concentrating on one country, we can uncover important local patterns. This shows the value of sharing expertise and ensuring that work of this nature is possible wherever this disease occurs.
Integrative single-cell meta-analysis reveals disease-relevant vascular cell states and markers in human atherosclerosis
Authors: Mosquera Jose Verdezoto , Auguste Gaëlle , Wong Doris , Turner Adam W. , Hodonsky Chani J. , Lino Cardenas Christian L. , Theofilatos Konstantinos , Bos Maxime , Kavousi Maryam , Peyser Patricia A. , Mayr Manuel , Kovacic Jason C. , Björkegren Johan L. M. , Malhotra Rajeev , van der Laan Sander W. , Zang Chongzhi , Sheffield Nathan C. , Miller Clint L.
Published: October 2022

Coronary artery disease (CAD) and atherosclerosis are characterized by plaque formation in the arteries wall. CAD progression involves complex interactions and phenotypic plasticity within and between distinct vascular and immune cell lineages. Single-cell RNA-seq (scRNA-seq) studies have highlighted lineage-specific transcriptomic signatures, but the reported cell phenotypes in humans remain controversial. Here, we meta-analyzed four scRNA-seq datasets, creating the first map of human cell diversity in atherosclerosis. We generated an atlas of 118,578 high-quality cells, characterized cell-type diversity and provided insights into smooth muscle cell (SMC) phenotypic modulation, transcription factor activity and cell-cell communication. We integrated genome-wide association study (GWAS) data and uncovered a critical role for modulated SMC phenotypes in CAD and coronary calcification. Finally, we identified candidate markers of fibromyocyte and fibrochondrogenic human SMCs (LTBP1andCRTAC1) that may serve as proxies of atherosclerosis progression. Altogether, we created a unified cellular map of atherosclerosis informing cell state-specific mechanistic and translational studies of cardiovascular diseases.
Modelling the distribution of rare and data-poor diadromous fish at sea for protected area management
Authors: Elliott Sophie A. M. , Acou Anthony , Beaulaton Laurent , Guitton Jérôme , Réveillac Elodie , Rivot Etienne
Published: October 2022

Anthropogenic pressures have resulted in declines in diadromous fish. Many diadromous fish which were commercially important are now threatened and protected. Little is known about their marine life history phases, and no observation-based Species Distribution Model exists for this group of species at sea. Yet, fisheries dependent and independent data could provide new insights into the distribution of diadromous fish at sea.

We collated a database of 168 904 hauls from fisheries observer bycatch data and scientific fisheries surveys, from eastern Atlantic and Mediterranean waters. The distribution of eleven rare and data-poor diadromous fish (shads, lampreys, salmonids, the European eel, the thinlip mullet, smelt and the European flounder) were modelled. A Bayesian site occupancy model, that incorporates imperfect detection to account for repeat detections and non-detections, the non-random nature of fishing gear type and spatial autocorrelation was used. From the model outputs, we explored bycatch risk and the role of MPAs, required under the Marine Strategy Framework Directive and Habitat Directive and assessed.

Diadromous fish were observed within relatively shallow coastal areas. Species specific gear bycatch trends were observed. Core distribution areas corresponded to their known water basin presence, indicating connectivity with their freshwater habitats. Numerous Habitat Directive Marine Protected Areas were found to be of relevance.

Given the coastal distribution of these species, they are exposed to higher anthropogenic pressures from both terrestrial and marine environments. Risk of bycatch at sea for most species appears to be low. Nonetheless, for threatened individuals, even a small amount of bycatch may impact their populations, especially since misreporting is likely to be high. Differences in catchability between gears highlight potential benefits of limiting access of certain gears within protected areas to reduce bycatch.
The Molecular Signatures Database Revisited: Extending Support for Mouse Data
Authors: Castanza Anthony S. , Recla Jill M. , Eby David , Thorvaldsdóttir Helga , Bult Carol J. , Mesirov Jill P.
Published: October 2022

The Molecular Signatures Database (MSigDB) serves as the primary repository of biological signature gene sets for performing Gene Set Enrichment Analysis (GSEA). In the more than 15 years since its creation, MSigDB has served over 290,000 users in their use of GSEA to perform statistically rigorous analysis of coordinated patterns of gene expression changes by leveraging the prior knowledge of tens of thousands of deposited signatures. In that time, the sets provided in MSigDB have been offered exclusively in the human gene space and only minimally supporting analysis of mouse model data through mapping to human genes. Here we present two substantial improvements to MSigDB: first, by providing gene sets from widely used resources in the mouse gene space; and second, by offering substantially improved orthology mapping resources for comparative analysis of both mouse and human datasets.
A cross-species proteomic map reveals neoteny of human synapse development
Authors: Wang Li , Pang Kaifang , Zhou Li , Cebrián-Silla Arantxa , González-Granero Susana , Wang Shaohui , Bi Qiuli , White Matthew L. , Ho Brandon , Li Jiani , Li Tao , Perez Yonatan , Huang Eric J. , Winkler Ethan A. , Paredes Mercedes F. , Kovner Rothem , Sestan Nenad , Pollen Alex A. , Liu Pengyuan , Li Jingjing , Piao Xianhua , García-Verdugo José Manuel , Alvarez-Buylla Arturo , Liu Zhandong , Kriegstein Arnold R.
Published: October 2022

The molecular mechanisms and evolutionary changes accompanying synapse development are still poorly understood. Here, we generated a cross-species proteomic map of synapse development in the human, macaque, and mouse neocortex. By tracking the changes of >1,000 postsynaptic density (PSD) proteins from midgestation to young adulthood, we found that PSD maturation in humans separates into three major phases that are dominated by distinct pathways. Cross-species comparisons reveal that the human PSD matures about two to three times slower than other species and contains higher levels of Rho guanine nucleotide exchange factors (RhoGEFs) in the perinatal period. Enhancement of the RhoGEF signaling in human neurons delays the morphological maturation of dendritic spines and the functional maturation of synapses, potentially contributing to the neotenic traits of human brain development. In addition, PSD proteins can be divided into four modules that exert stage- and cell type-specific functions, possibly explaining their differential associations with cognitive functions and diseases. Together, our proteomic map of synapse development provides a blueprint for studying the molecular basis and evolutionary changes of synapse maturation.
Developmental staging and future research directions of the model marine tubewormHydroides elegans
Authors: Nesbit Katherine T. , Shikuma Nicholas J.
Published: October 2022

Background

The biofouling marine tube worm,Hydroides elegans, is an indirect developing polychaete with significance as a model organism for questions in developmental biology and the evolution of host-microbe interactions. However, a complete description of the life cycle from fertilization through sexual maturity remains scattered in the literature, and lacks standardization.

Results

Here we present a unified staging scheme detailing the major morphological changes that occur during the entire life cycle of the animal. These data represent a complete record of the life cycle, and serve as a foundation for connecting molecular changes with morphology.

Conclusions

The present descriptions and associated staging scheme are especially timely as this system gains traction within research communities. Characterizing theHydroideslife cycle is essential for investigating the molecular mechanisms that drive major developmental transitions, like metamorphosis, in response to bacteria.
NDEx IQuery: a multi-method network gene set analysis leveraging the Network Data Exchange
Authors: Pillich RT , Chen J , Churas C , Fong D , Ideker T , Liu SN , Gyori BM , Karis K , Ono K , Pico A , Pratt D
Published: October 2022

Motivation

The investigation of sets of genes using biological pathways is a common task for researchers and is supported by a wide variety of software tools. This type of analysis generates hypotheses about the biological processes active or modulated in a specific experimental context.

Results

The NDEx Integrated Query (IQuery) is a new tool for network and pathway-based gene set interpretation that complements or extends existing resources. It combines novel sources of pathways, integration with Cytoscape, and the ability to store and share analysis results. The IQuery web application performs multiple gene set analyses based on diverse pathways and networks stored in NDEx. These include curated pathways from WikiPathways and SIGNOR, published pathway figures from the last 27 years, machine-assembled networks using the INDRA system, and the new NCI-PID v2.0, an updated version of the popular NCI Pathway Interaction Database. IQuery’s integration with MSigDB and cBioPortal now provides pathway analysis in the context of these two resources.

Availability and Implementation

IQuery is available athttps://www.ndexbio.org/iqueryand is implemented in Javascript and Java.

Contact

Dexter Pratt (depratt@health.ucsd.edu)
Extraction Optimization, Characterization, and Antioxidant Capacity of Phenolics from Cowpeas (Vigna Unguiculata)
Authors: Webber Daniel M. , Hettiarachchy Navam S. , Horax Ronny
Published: October 2022

Ethanol-water extraction of phenolics from cowpeas was modeled and optimized by response surface methodology (RSM). The ethanol concentration and extraction temperature were shown to have a significant effect on phenolic extraction and antioxidant capacity. Modeling predicted that extraction of phenolics from cowpea flour for 42.8 minutes at 58.6°C with 58.4% ethanol would maximize the radical scavenging capacity of solutes. Extraction of phenolics under these optimized conditions yielded 11.05 ± 0.10 mg chlorogenic acid equivalents (CAE)/g cowpea flour. These extracts contained 10.41 % ± 0.11% phenolics by weight and had an antioxidant capacity of 0.45 ± 0.02, closely approximating the predicted phenolic content of 10.11% ± 0.44% and antioxidant capacity of 0.42 ± 0.04. Extracted material was characterized by HPLC, and the predominant phenolic compounds detected were epicatechin and ferulic acid. Cowpea’s low cost, ease of storage, and high antioxidant capacity reflect their potential for use as a naturally-derived antioxidant additive in foods.
A Taxonomy of Seizure Spread Patterns, Speed of Spread, and Associations With Structural Connectivity
Authors: Revell Andrew Y. , Pattnaik Akash R. , Conrad Erin , Sinha Nishant , Scheid Brittany H. , Lucas Alfredo , Bernabei John M. , Beckerle John , Stein Joel M. , Das Sandhitsu R. , Litt Brian , Davis Kathryn A.
Published: October 2022

Although seizure detection algorithms are widely used to localize seizure onset on intracranial EEG in epilepsy patients, relatively few studies focus on seizure activity beyond the seizure onset zone to direct treatment of surgical patients with epilepsy. To address this gap, we develop and compare fully automated deep learning algorithms to detect seizure activity on single channels, effectively quantifying spread when deployed across multiple channels. Across 275 seizures in 71 patients, we discover that the extent of seizure spread across the brain and the timing of seizure spread between temporal lobe regions is associated with both surgical outcomes and the brain’s structural connectivity between temporal lobes. Finally, we uncover a hierarchical structure of seizure spread patterns highlighting the relationship between clusters of seizures. Collectively, these findings underscore the broad utility in quantifying seizure activity past seizure onset to identify novel mechanisms of seizure evolution and its relationship to potential seizure freedom.
The role of consciously timed movements in shaping and improving auditory timing
Authors: De Kock Rose , Zhou Weiwei , Datta Poorvi , Joiner Wilsaan Mychal , Wiener Martin
Published: October 2022

Our subjective sense of time is intertwined with a plethora of perceptual, cognitive, and motor functions, and likewise, the brain is equipped to expertly filter, weight, and combine these signals for seamless interactions with a dynamic world. Until relatively recently, the literature on time perception has excluded the influence of motor activity, yet, it has been found that motor circuits in the brain are at the core of most timing functions. Several studies have now identified that concurrent movements exert robust effects on perceptual timing estimates, but critically, have not assessed how humans consciously judge the duration of their own movements. This creates a gap in our understanding of the mechanisms driving movement-related effects on sensory timing. We sought to address this gap by administering a sensorimotor timing task in which we explicitly compared the timing of isolated auditory tones and arm movements, or both simultaneously. We contextualized our findings within a Bayesian cue combination framework, in which separate sources of temporal information are weighted by their reliability and integrated into a unitary time estimate that is more precise than either unisensory estimate. Our results revealed differences in accuracy between auditory, movement, and combined trials, and crucially, that combined trials were the most accurately timed. Under the Bayesian framework, we found that participants’ combined estimates were more precise than isolated estimates in a way that trended towards optimality, while being overall less optimal than the model’s prediction. These findings elucidate previously unknown qualities of conscious motor timing, and proposes computational mechanisms that can describe how movements combine with perceptual signals to create unified, multimodal experiences of time.
Bayesian Accounts of Perceptual Decisions in the Nonclinical Continuum of Psychosis: Greater Imprecision in Both Top-down and Bottom-up Processes
Authors: Goodwin Isabella , Kugel Joshua , Hester Robert , Garrido Marta I.
Published: October 2022

Neurocomputational accounts of psychosis propose mechanisms for how information is integrated into a predictive model of the world, in attempts to understand the occurrence of altered perceptual experiences. Conflicting Bayesian theories postulate aberrations in either top-down or bottom-up processing. The top-down theory predicts an overreliance on prior beliefs or expectations resulting in aberrant perceptual experiences, whereas the bottom-up theory predicts an overreliance on current sensory information, as aberrant salience is directed towards objectively uninformative stimuli. This study empirically adjudicates between these models. We use a perceptual decision-making task in a neurotypical population with varying degrees of psychotic-like experiences. Bayesian modelling was used to compute individuals’ reliance on prior relative to sensory information. Across two datasets (discovery dataset n=363; independent replication in validation dataset n=782) we showed that psychotic-like experiences were associated with an overweighting of sensory information relative to prior expectations, which seem to be driven by decreased precision afforded to prior information. However, when prior information was more uncertain, participants with greater psychotic-like experiences encoded sensory information with greater noise. Greater psychotic-like experiences were also associated with generally heightened perceptions of task instability, which we suggest may be the cause for the observed aberrant precision in the encoding both prior and likelihood information. Our study lends empirical support to notions of both weaker bottom-up and weaker (rather than stronger) top-down perceptual processes, as well as aberrancies in belief updating that extend into the non-clinical continuum of psychosis.
Ratio-based quantitative multiomics profiling using universal reference materials empowers data integration
Authors: Zheng Yuanting , Liu Yaqing , Yang Jingcheng , Dong Lianhua , Zhang Rui , Tian Sha , Yu Ying , Ren Luyao , Hou Wanwan , Zhu Feng , Mai Yuanbang , Han Jinxiong , Zhang Lijun , Jiang Hui , Lin Ling , Lou Jingwei , Li Ruiqiang , Lin Jingchao , Liu Huafen , Kong Ziqing , Wang Depeng , Dai Fangping , Bao Ding , Cao Zehui , Chen Qiaochu , Chen Qingwang , Chen Xingdong , Gao Yuechen , Jiang He , Li Bin , Li Bingying , Li Jingjing , Liu Ruimei , Qing Tao , Shang Erfei , Shang Jun , Sun Shanyue , Wang Haiyan , Wang Xiaolin , Zhang Naixin , Zhang Peipei , Zhang Ruolan , Zhu Sibo , Scherer Andreas , Wang Jiucun , Wang Jing , Xu Joshua , Hong Huixiao , Xiao Wenming , Liang Xiaozhen , Jin Li ,   The Quartet Project Team, Tong Weida , Ding Chen , Li Jinming , Fang Xiang , Shi Leming
Published: October 2022

Multiomics profiling is a powerful tool to characterize the same samples with complementary features orchestrating the genome, epigenome, transcriptome, proteome, and metabolome. However, the lack of ground truth hampers the objective assessment of and subsequent choice from a plethora of measurement and computational methods aiming to integrate diverse and often enigmatically incomparable omics datasets. Here we establish and characterize the first suites of publicly available multiomics reference materials of matched DNA, RNA, proteins, and metabolites derived from immortalized cell lines from a family quartet of parents and monozygotic twin daughters, providing built-in truth defined by family relationship and the central dogma. We demonstrate that the “ratio”-based omics profiling data,i.e., by scaling the absolute feature values of a study sample relative to those of a concurrently measured universal reference sample, were inherently much more reproducible and comparable across batches, labs, platforms, and omics types, thus empower the horizontal (within-omics) and vertical (cross-omics) data integration in multiomics studies. Our study identifies “absolute” feature quantitation as the root cause of irreproducibility in multiomics measurement and data integration, and urges a paradigm shift from “absolute” to “ratio"-based multiomics profiling with universal reference materials.
Neuroinvasive flavivirus pathogenesis is restricted by host genetic factors in Collaborative Cross mice, independently of Oas1b
Authors: Jasperse Brittany A. , Mattocks Melissa D. , Noll Kelsey M. , Ferris Martin T. , Heise Mark T. , Lazear Helen M.
Published: October 2022

Powassan virus (POWV) is an emerging tick-borne flavivirus that causes neuroinvasive disease, including encephalitis, meningitis, and paralysis. Similar to other neuroinvasive flaviviruses, such as West Nile virus (WNV) and Japanese encephalitis virus (JEV), POWV disease presentation is heterogeneous, and the factors influencing disease outcome are not fully understood. We used Collaborative Cross (CC) mice to assess the impact of host genetic factors on POWV pathogenesis. We infected a panel ofOas1b-null CC lines with POWV and observed a range of susceptibility phenotypes, indicating that host factors other than the well-characterized flavivirus restriction factorOas1bmodulate POWV pathogenesis in CC mice. AmongOas1b-null CC lines, we identified multiple highly susceptible lines (0% survival), including CC071, and a single resistant line (78% survival), CC045. Susceptibility phenotypes generally were concordant among neuroinvasive flaviviruses, although we identified one line, CC006, that was resistant specifically to JEV, suggesting that both pan-flavivirus and virus-specific mechanisms contribute to susceptibility phenotypes in CC mice. We found that POWV replicated to higher titers in bone marrow-derived macrophages from CC071 mice compared to CC045 mice, suggesting that resistance could result from cell-intrinsic restriction of viral replication. Although serum viral loads at 2 days post-infection were equivalent between CC071 and CC045 mice, clearance of POWV from the serum was significantly slower in CC071 mice. Furthermore, CC045 mice had significantly lower viral loads in the brain at 7 days post-infection compared to CC071 mice, suggesting that reduced CNS infection contributes to the resistant phenotype of CC045 mice.

IMPORTANCE

Neuroinvasive flaviviruses, such as WNV, JEV, and POWV, are transmitted to humans by mosquitoes or ticks, can cause neurologic disease, such as encephalitis, meningitis, and paralysis, and can result in death or long-term sequelae. Although potentially severe, neuroinvasive disease is a rare outcome of flavivirus infection. The factors that determine whether someone develops severe disease after flavivirus infection are not fully understood, but host genetic differences in polymorphic antiviral response genes likely contribute to disease outcome. We evaluated a panel of genetically diverse mice and identified lines with distinct outcomes following infection with POWV. We found that resistance to POWV pathogenesis corresponded to reduced viral replication in macrophages, more rapid clearance of virus in peripheral tissues, and reduced viral infection in the brain. These susceptible and resistant mouse lines will provide a system for investigating the pathogenic mechanisms of POWV and identifying polymorphic host genes that contribute to resistance.
Consistent Under-reporting of Task Details in Motor Imagery Research
Authors: Van Caenegem Elise E , Hamoline Gautier , Waltzing Baptiste M , Hardwick Robert M
Published: October 2022

Motor Imagery is a subject of longstanding scientific interest. However, critical details of motor imagery protocols are not always reported in full, hampering direct replication and translation of this work. The present review provides a quantitative assessment of the prevalence of under-reporting in the recent motor imagery literature. Publications from the years 2018-2020 were examined, with 695 meeting the inclusion criteria for further examination. Of these studies, 64% (445/695) did not provide information about the modality of motor imagery (i.e., kinesthetic, visual, or a mixture of both) used in the study. When visual or mixed imagery was specified, the details of the visual perspective to be used (i.e., first person, third person, or combinations of both) were not reported in 24% (25/103) of studies. Further analysis indicated that studies using questionnaires to assess motor imagery reported more information than those that did not. We conclude that studies using motor imagery consistently under-report key details of their protocols, which poses a significant problem for understanding, replicating, and translating motor imagery effects.
Identification of Tumor Antigens and Immune Subtypes of Acute Myeloid Leukemia for mRNA Vaccine Development
Authors: Wang Fan
Published: October 2022

Background

Acute myeloid leukemia (AML) is a highly aggressive hematological malignancy, and there has not been any significant improvement in therapy of AML over the past several decades. The mRNA vaccines have become a promising strategy against multiple cancers, however, its application on AML remains undefined. In this study, we aimed to identify novel antigens for developing mRNA vaccines against AML and explore the immune landscape of AML to select appropriate patients for vaccination.

Methods

The genomic data and clinical information were retrieved from TCGA and GEO, respectively. The gene mutation data of AML were obtained from cBioPortal. GEPIA2 was used to analyze differentially expressed genes. The single cell RNA-seq database Tumor Immune Single-cell Hub (TISCH) was used to explore the association between the potential tumor antigens and the infiltrating immune cells in the bone marrow. Consensus clustering analysis was applied to identify distinct immune subtypes. The correlation between the abundance of antigen presenting cells and the expression level of antigens was evaluated using Spearman correlation analysis. The characteristics of the tumor immune microenvironment in each subtype were investigated based on single-sample gene set enrichment analysis. Weighted gene co-expression network analysis (WGCNA) was performed to identify co-expression modules and screen the hub genes.

Results

Five potential tumor antigens were identified for mRNA vaccine from the pool of overexpressed and mutated genes, including CDH23, LRP1, MEFV, MYOF and SLC9A9, which were associated with infiltration of antigen-presenting immune cells (APCs). AML patients were stratified into two immune subtypes Cluster1 (C1) and Cluster2 (C2), which were characterized by distinct molecular and clinical features. Patients with C1 subtype showed higher expression level of the five candidate genes and worse prognosis compared with C2 subtype. Moreover, C1 subtype demonstrated an immune-hot and immunosuppressive phenotype, while the C1 subtype had an immune-cold phenotype. Furthermore, the two immune subtype showed remarkably different expression of immune checkpoints, immunogenic cell death modulators and human leukocyte antigens. Finally, WCGNA identified a module and five hub genes that can be used for predicting the response of AML patients to mRNA vaccine.

Conclusion

CDH23, LRP1, MEFV, MYOF and SLC9A9 were potential antigens for developing AML mRNA vaccine, and AML patients in immune subtype 1 were suitable for vaccination.
Transmission ofXylella fastidiosasubsp. pauca ST53 by the sharpshooterCicadella viridisfrom different source plants and artificial diets
Authors: Bodino Nicola , Cavalieri Vincenzo , Saponari Maria , Dongiovanni Crescenza , Altamura Giuseppe , Bosco Domenico
Published: October 2022

The sharpshooterCicadella viridisL. (Hemiptera: Cicadellidae) is the most common sharpshooter in Europe and, given its xylem feeding behaviour, is considered a potential vector of the plant pathogenic bacteriumXylella fastidiosaWells et al. (Xanthomonadales:Xanthomonadaceae). We testedX. fastidiosasubsp. pauca ST53 (Xfp) transmission capabilities ofC. viridisadults, namely i) acquisition efficiency from four host plant species – periwinkle, milkwort, lavender, alfalfa – and from two artificial diets (PD3 and Xfm), ii) inoculation efficiency to periwinkle at different times post acquisition from different plant and artificial diet sources. The main European vector species –Philaenus spumarius– was used as a control.Cicadella viridiswas able to acquireXfpfrom periwinkle, milkwort, and lavender, although with low efficiency (3–16%) and from artificial diets (23–25%). Successful inoculation on periwinkle was extremely rare, being observed only three times, following feeding on milkwort plant and PD3 artificial diet sources. Our study shows thatC. viridisis not a relevant vector ofXfp, given the very low transmission rate in controlled conditions and the inability to feed on olive. The low efficiency reported here sums also to ecological constraints (mainly monocots host plants, humid environments) that make difficult to forecast a relevant role in dispersingX. fastidiosa, at least within the present distribution of the exotic bacterium in Europe. However, a possible role of this species in spreadingXfin other agroecosystems, e.g. vineyard and stone fruits grown in humid areas, cannot be excluded.
mutscan - a flexible R package for efficient end-to-end analysis of multiplexed assays of variant effect data
Authors: Soneson Charlotte , Bendel Alexandra M , Diss Guillaume , Stadler Michael B
Published: October 2022

Multiplexed assays of variant effect (MAVE) experimentally measure the fitness of large numbers of sequence variants by selective enrichment of sequences with desirable properties followed by quantification by sequencing.mutscanis an R package for flexible analysis of such experiments, covering the entire workflow from raw reads up to statistical analysis and visualization. Core components are implemented in C++ for efficiency. Various experimental designs are supported, including single or paired reads with optional unique molecular identifiers. To find variants with changed relative abundance,mutscanemploys established statistical models provided in theedgeRandlimmapackages.mutscanis available fromhttps://github.com/fmicompbio/mutscan.
Nuclear proteins acquiring Germinal Center B cells are specifically suppressed by follicular regulatory T cells
Authors: Ke Fang , Benet Zachary L. , Maz Mitra P. , Liu Jianhua , Dent Alexander L. , Kahlenberg J. Michelle , Grigorova Irina L.
Published: October 2022

Follicular regulatory T cells (Tfrs) restrict development of autoantibodies and autoimmunity while supporting high-affinity foreign antigen-specific humoral response. However, whether Tfrs can directly repress germinal center (GC) B cells that acquire auto-antigens is unclear. Moreover, TCR specificity of Tfrs to self-antigens is not known. Our study suggests that nuclear proteins contain antigens specific to Tfrs. Targeting of these proteins to antigen-specific B cells triggers rapid accumulation of Tfrs with immunosuppressive characteristics. Tfrs then exert negative regulation of GC B cells with predominant inhibition of the nuclear protein-acquiring GC B cells, suggesting an important role of direct cognate Tfr-GC B cells interactions for the control of effector B cell response.
Multi-species analysis of inflammatory response elements reveals ancient and lineage-specific contributions of transposable elements to NF-κB binding
Authors: Wang Liangxi , Taylor Tiegh , Rathnakumar Kumaragurubaran , Khyzha Nadiya , Liang Minggao , Alizada Azad , Campitelli Laura , Pour Sara E , Patel Zain M , Antounians Lina , Tobias Ian C , Hughes Timothy , Roy Sushmita , Mitchell Jennifer A , Fish Jason E , Wilson Michael D
Published: October 2022

Transposable elements (TEs) provide a source of transcription factor binding sites that can rewire conserved gene regulatory networks. NF-κB is an evolutionary conserved transcription factor complex primarily involved in innate immunity and inflammation. The extent to which TEs have contributed to NF-κB responses during mammalian evolution is not well established. Here we performed a multi-species analysis of TEs bound by the NF-κB subunit RELA (also known as p65) in response to the proinflammatory cytokine TNF. By comparing RELA ChIP-seq data from TNF-stimulated primary aortic endothelial cells isolated from human, mouse and cow, we found that 55 TE subfamilies were associated with RELA bound regions. These RELA-bound transposons possess active epigenetic features and reside near TNF-responsive genes. A prominent example of lineage-specific contribution of transposons comes from the bovine SINE subfamilies Bov-tA1/2/3 which collectively contributed over 14,000 RELA bound regions in cow. By comparing RELA binding data across species, we also found several examples of RELA motif-bearing TEs that colonized the genome prior to the divergence of the three species and contributed to species-specific RELA binding. For example, we found human RELA bound MER81 instances were enriched for the interferon gamma pathway and demonstrated that one RELA bound MER81 element can control the TNF-induced expression of Interferon Gamma Receptor 2 (IFNGR2). Using ancestral reconstructions, we found that RELA containing MER81 instances rapidly decayed during early primate evolution (> 50 million years ago (MYA)) before stabilizing since the separation of Old World monkeys (< 50 MYA). Taken together, our results suggest ancient and lineage-specific transposon subfamilies contributed to mammalian NF-κB regulatory networks.