bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinctive Nested Glomoid Neoplasm
Authors: Papke David J. , Dickson Brendan C. , Oliveira Andre M. , Sholl Lynette M. , Fletcher Christopher D.M.
Published: November 2022

Recently, it has been recognized that a subset of primary soft tissue neoplasms with GLI1 gene alterations exhibit nested architecture and can mimic glomus tumors or well-differentiated neuroendocrine tumors. Here, we report a series of 20 such neoplasms, which we have provisionally termed “distinctive nested glomoid neoplasm.” Eleven patients (55%) were female and 9 were male. The median age at presentation was 41.5 years (range: congenital to 74 y). The anatomic distribution was wide, with body sites including the trunk (7 tumors), lower extremity (5), tongue (4), upper extremity (3), and neck (1). Excluding tumors of the tongue, 10 tumors (62%) arose in deep soft tissue and 6 (38%) arose primarily in the subcutis. Tumor size ranged from 0.9 to 11.1 cm (median: 3 cm). Distinctive nested glomoid neoplasms are composed of nests of round-to-ovoid cells with scant, palely eosinophilic cytoplasm and monomorphic nuclei with vesicular chromatin and small nucleoli. The nests are invested by prominent capillary networks, and they are situated within large lobules separated by irregular, thick fibrous septa. Among 18 tumors for which adjacent non-neoplastic tissue could be assessed, perivascular proliferation of tumor cells was identified in 16 tumors (89%). Microcystic architecture was present at least focally in 8 tumors (40%), and myxoid stroma was identified at least focally in 5 (25%). Seven tumors (35%) showed clear cell features. By immunohistochemistry, some tumors expressed MDM2 (7/15; 47%), S100 (5 of 19; 26%), STAT6 (2 of 5; 20%), and AE1/AE3 (1/5; 20%). Tumors rarely expressed pan-keratin (1/10; 10%) or CAM5.2 (1/10), and all tumors were negative for β-catenin (12 tumors), chromogranin (12), synaptophysin (11), epithelial membrane antigen (10), desmin (10), smooth muscle actin (9), INSM1 (7), and CD34 (6). GLI1 break-apart fluorescence in situ hybridization was performed on 7 tumors, and next-generation sequencing was performed on 15 tumors (10 DNA sequencing only, 1 RNA sequencing only, 4 both DNA and RNA sequencing). Sixteen tumors, including all 15 tested by next-generation sequencing and an additional case tested by fluorescence in situ hybridization only, were found to harbor GLI1 gene alterations: 10 harbored GLI1 gene rearrangements (3 ACTB::GLI1, 2 PTCH1::GLI1, 1 HNRNPA1::GLI1, 1 NEAT1::GLI1, 1 TXNIP::GLI1, 2 undetermined fusion partners), and 6 harbored GLI1 amplification. Clinical follow-up was available for 10 patients (50%; range: 3 mo to 10 y; median: 6.4 y), including 8 with >1 year of follow-up. Three patients (30%) experienced local recurrence (at intervals of 3 mo to 10 y). None developed distant metastases or died of disease as yet. Overall, our findings support the notion that a subset of GLI1-altered soft tissue neoplasms are indolent, morphologically distinctive nested glomoid neoplasms that should not be classified as sarcomas.
Core Needle Biopsy in Lymphoma Diagnosis
Authors: Gonçalves Marianne de C. , de Oliveira Claudia Regina G.C.M. , Sandes Alex F. , Rodrigues Celso A. , Novis Yana , Viana Públio C.C. , Serra Márcia M.P. , Zerbini Maria Claudia N.
Published: November 2022

To compare the diagnostic accuracy of core needle biopsies (CNBs) and surgical excisional biopsies (SEBs), samples of lymphoid proliferation from a single institution from 2013 to 2017 (N=476) were divided into groups of CNB (N=218) and SEB (N=258). The diagnostic accuracy of these samples was evaluated as a percentage of conclusive diagnosis, according to the World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. The contribution of clinical data, the assessment of sample adequacy by a pathologist during the procedure, the number and size of fragments, the needle gauge, the ancillary tests, and the type of lymphoid proliferation were also examined. The diagnostic accuracy of SEB was 97.3% and CNB 91.3% (P=0.010). Additional factors considered essential for establishing the final diagnosis in some cases were: clinical information (20.6% CNB, 7.4% SEB; P<0.001); immunohistochemistry (96.3% CNB, 91.5% SEB; P=0.024); flow cytometry (12% CNB, 6.8% SEB; P=0.165); and other complementary tests (8.2% CNB, 17.3% SEB; P=0.058). Factors that did not influence performance were the evaluation of sample adequacy during the procedure, the number and size of fragments, and the needle gauge. Increased percentage of nondiagnostic CNB was observed in T-cell lymphomas (30%), followed by classic Hodgkin lymphoma (10.6%). The main limitation of CNB was the evaluation of morphologically heterogenous diseases. CNB is useful and safe in lymphoma diagnosis provided it is carried out by a team of experienced professionals. Having an interventional radiology team engaged with pathology is an essential component to achieve adequate rates of specific diagnoses in CNB specimens.
MUSCLE SYNERGIES ANALYSIS SHOWS ALTERED NEURAL COMMANDS IN WOMEN WITH PATELLOFEMORAL PAIN DURING WALKING
Authors: Ferreira Cintia Lopes , Barroso Filipe O. , Torricelli Diego , Pons José L. , Politti Fabiano , Lucareli Paulo Roberto Garcia
Published: November 2022

Backgroud

Several studies suggest that the central nervous system coordinates muscle activation by modulating neural commands directed to groups of muscles combined to form muscle synergies. Individuals with patellofemoral pain (PFP) move differently from asymptomatic individuals. Understanding the neural factors involved in the execution of tasks such as walking can help comprehend how the movement is planned and better understand this clinical condition.

Research question

To compare the muscle coordination of women with and without PFP during gait.

Methods

Eleven women with PFP and thirteen asymptomatic women were assessed using three-dimensional kinematics and electromyography (EMG) while walking at self-selected speed. Kinematics of the trunk, pelvis and lower limbs were analyzed through the Movement Deviation Profile. Muscle synergies were extracted from the EMG signals of eight lower limb muscles collected throughout the whole gait cycle.

Results

Kinematic differences between the two groups (p<0.001, z-score=3.06) were more evident during loading response, terminal stance, and pre-swing. PFP group presented a lower number of muscle synergies (p=0.037), and greater variability accounted for (VAFtotal) when using 3 (p=0.017), 4 (p=0.004), and 5 (p=0.012) synergies to reconstruct all EMG signals. The PFP group also presented higher VAFmusclefor rectus femoris (p=0.048) and gastrocnemius medialis (p=0.019) when considering 4 synergies.

Significance

Our results suggest that women with PFP show lower motor complexity and deficit in muscle coordination to execute gait, indicating that gait in PFP gait is the result of different neural commands compared to asymptomatic women.
Observational methods for COVID-19 vaccine effectiveness research: a trial emulation and empirical evaluation
Authors: Català Martí , Burn Edward , Rathod-Mistry Trishna , Xie Junqing , Delmestri Antonella , Prieto-Alhambra Daniel , Jödicke Annika M.
Published: November 2022

Despite much research on the topic, little work has been done comparing the use of methods to control for confounding in the estimation of COVID-19 vaccine effectiveness in routinely collected medical record data. We conducted a trial emulation study to replicate the ChAdOx1 (Oxford/AstraZeneca) and BNT162b2 (BioNTech/Pfizer) COVID-19 phase 3 efficacy studies. We conducted a cohort study including individuals aged 75+ from UK CPRD AURUM (N = 916,128) in early 2021. Three different methods were assessed: Overlap weighting, inverse probability treatment weighting, and propensity score matching. All three methods successfully replicated the findings from both phase 3 trials, and overlap weighting performed best in terms of confounding, systematic error, and precision. Despite lack of trial data beyond 3 weeks, we found that even 1 dose of BNT162b2 was effective against SARS-CoV-2 infection for up to 12 weeks before a second dose was administered. These results support the UK Joint Committee on Vaccination and Immunisation modelling and related UK vaccination strategies implemented in early 2021.

Key messages

Real world evidence generated using weighting (overlapping weights and inverse probability of treatment weights) and propensity score matching: all methods successfully replicate the findings of Phase 3 trials for COVID-19 vaccine effectiveness.

Overlap weighting provides the least biased estimates in our study and should be considered amongst the most suitable methods for future COVID-19 vaccine effectiveness research.

Despite a lack of trial data, our findings suggest that first-dose BNT162b2 provides effective protection against SARS-COV-2 infection for up to 12 weeks, in line with UK’s Joint Committee on Vaccination and Immunisation modelling and subsequent vaccination strategies.
Never let me down: new possibilities for lowering serum free cultivation media costs
Authors: Schenzle Lisa , Egger Kristina , Spangl Bernhard , Hussein Mohamed , Ebrahimian Atefeh , Kuehnel Harald , Ferreira Frederico C. , Marques Diana M. C. , Berchtold Beate , Borth Nicole , Fuchs Aleksandra , Pichler Harald
Published: November 2022

Cultivated meat may be a more ethical, environmentally friendly, antibiotic-free meat alternative of the future. As of now, one of the main limiting factors for bringing cultivated meat to the market is the high cost of the cell culture media and their great dependency on serum albumins, production of which is predicted to become a major bottleneck of this industry. Here, using bovine muscle stem cells (BSC) we optimized B8/B9 medium - one of the well-established serum free, fully defined medium compositions available for purchase or for preparation in-house. We show several combinations of the growth factors/myokines/hormones, which were able to substantially increase BSCs proliferation rate, as well as treatment schemes allowing for five to ten times lower concentrations of signaling molecules for the same effect. Additionally, we identified several food grade, low-price medium stabilizers, exhibiting comparable or even superior stabilization of the B8 medium in short-term cultivations, as compared to recombinant human serum albumin (HSA). DoE aided in identifying the best cultivation conditions. Other satellite cells (porcine, chicken and fish) were grown in several final cell culture medium compositions, showing significant cell-line specific differences in performance. Also, the proliferation and yield of CHO cell line, which is relevant e.g. for the production of growth factors, was also successfully increased using our stabilization approach. We conclude that stabilizers tested here can act as versatile low-cost medium additives, partly by prolonging the half-life of growth factors. Thus, we provide an alternative to HSA, enabling up to an overall 73% reduction of medium price.
Global spatiotemporal trends and determinants of COVID-19 vaccine acceptance on Twitter: a multilingual deep learning study in 135 countries and territories
Authors: Zhou Xinyu , Zhang Xu , Larson Heidi J. , de Figueiredo Alexandre , Jit Mark , Fodeh Samah , Vermund Sten H. , Zang Sujie , Lin Leesa , Hou Zhiyuan
Published: November 2022

Background

COVID-19 vaccination has faced a range of challenges from supply-side barriers such as insufficient vaccine supply and negative information environment and demand-side barriers centring on public acceptance and confidence in vaccines. This study assessed global spatiotemporal trends in demand- and supply-side barriers to vaccine uptake using COVID-19-related social media data and explored the country-level determinants of vaccine acceptance.

Methods

We accessed a total of 13,093,406 tweets sent between November 2020 and March 2022 about the COVID-19 vaccine in 90 languages from 135 countries using Meltwater™® (a social listening platform). Based on 8,125 manually-annotated tweets, we fine-tuned multilingual deep learning models to automatically annotate all 13,093,406 tweets. We present spatial and temporal trends in four key spheres: (1) COVID-19 vaccine acceptance; (2) confidence in COVID-19 vaccines; (3) the online information environment regarding the COVID-19 vaccine; and (4) perceived supply-side barriers to COVID-19 vaccination. Using univariate and multilevel regressions, we evaluated the association between COVID-19 vaccine acceptance on Twitter® and (1) country-level characteristics regarding governance, pandemic preparedness, trust, culture, social development, and population demographics; (2) country-level COVID-19 vaccine coverage; and (3) Google® search trends on adverse vaccine events.

Findings

COVID-19 vaccine acceptance was high among Twitter® users in Southeast Asian, Eastern Mediterranean, and Western Pacific countries, including India, Indonesia, and Pakistan. In contrast, acceptance was relatively low in high-income nations like South Korea, Japan, and the Netherlands. Spatial variations were correlated with country-level governance, pandemic preparedness, public trust, culture, social development, and demographic determinants. At the country level, vaccine acceptance sentiments expressed on Twitter® predicted higher vaccine coverage. We noted the declining trend of COVID-19 vaccine acceptance among global Twitter® users since March 2021, which was associated with increased searches for adverse vaccine events.InterpretationIn future pandemics, new vaccines may face the potential low-level and declining trend in acceptance, like COVID-19 vaccines, and early responses are needed. Social media mining represents a promising surveillance approach to monitor vaccine acceptance and can be validated against real-world vaccine uptake data.

Funding

National Natural Science Foundation of China.
Versatile detection of diverse selective sweeps with Flex-sweep
Authors: Lauterbur M. Elise , Munch Kasper , Enard David
Published: November 2022

Understanding the impacts of selection pressures influencing modern-day genomic diversity is a major goal of evolutionary genomics. In particular, the contribution of selective sweeps to adaptation remains an open question, with persistent statistical limitations on the power and specificity of sweep detection methods. Sweeps with subtle genomic signals have been particularly challenging to detect. While many existing methods powerfully detect specific types of sweeps and/or those with strong signals, their power comes at the expense of versatility. We present Flex-sweep, a machine learning-based tool designed to detect sweeps with a variety of subtle signals, including those thousands of generations old. It is especially valuable for non-model organisms, for which we have neither expectations about the overall characteristics of sweeps nor outgroups with population-level sequencing to otherwise facilitate detecting very old sweeps. We show that Flex-sweep has the power to detect sweeps with subtle signals, even in the face of demographic model misspecification, recombination rate heterogeneity, and background selection. Flex-sweep detects sweeps up to 0.125 * 4Negenerations old, including those that are weak, soft, and/or incomplete; it can also detect strong, complete sweeps up to 0.25 * 4Negenerations old. We apply Flex-sweep to the 1000 Genomes Yoruba data set and, in addition to recovering previously identified sweeps, show that sweeps disproportionately occur within genic regions and close to regulatory regions. In addition, we show that virus-interacting proteins (VIPs) are strongly enriched for selective sweeps, recapitulating previous results that demonstrate the importance of viruses as a driver of adaptive evolution in humans.
Diverging trends and drivers of Arctic flower production over space and time
Authors: Becker-Scarpitta Antoine , Antão Laura H. , Martin Schmidt Niels , Blanchet F. Guillaume , Kaarlejärvi Elina , Raundrup Katrine , Roslin Tomas
Published: November 2022

The Arctic is warming at an alarming rate. While changes in plant community composition and phenology have been extensively reported, the effects of climate change on reproduction remain poorly understood. We quantified multidecadal changes in flower density for nine tundra plant species at a low- and a high-arctic site in Greenland. We found substantial changes in flower density over time, but the temporal trends and drivers of flower density differed both between species and sites. Total flower density increased over time at the low-arctic site, whereas the high-arctic site showed no directional change. Within and between sites, the direction and rate of change differed among species, with varying effects of summer temperature, the temperature of the previous autumn and the timing of snowmelt. Finally, all species showed a strong trade-off in flower densities between successive years, suggesting an effective cost of reproduction. Overall, our results reveal region-and taxon-specific variation in the sensitivity and responses of co-occurring species to shared climatic drivers, and a clear cost of reproductive investment among arctic plants. The ultimate effects of further changes in climate may thus be decoupled between species and across space, with critical knock-on effects on plant species dynamics, food web structure and overall ecosystem functioning.
ChromFormer: A transformer-based model for 3D genome structure prediction
Authors: Valeyre Henry , Pati Pushpak , Gossi Federico , Somnath Vignesh Ram , Martinelli Adriano , Rapsomaniki Maria Anna
Published: November 2022

Recent research has shown that the three-dimensional (3D) genome structure is strongly linked to cell function. Modeling the 3D genome structure can not only elucidate vital biological processes, but also reveal structural disruptions linked to disease. In the absence of experimental techniques able to determine 3D chromatin structure, this task is achieved computationally by exploiting chromatin interaction frequencies as measured by high-throughput chromosome conformation capture (Hi-C) data. However, existing methods are unsupervised, and limited by underlying assumptions. In this work, we present a novel framework for 3D chromatin structure prediction from Hi-C data. The framework consists of, a novelsynthetic data generation modulethat simulates realistic structures and corresponding Hi-C matrices, and ChromFormer, a transformer-based model to predict 3D chromatin structures from standalone Hi-C data, while providing local structural-level confidence estimates. Our solution outperforms existing methods when tested on unseen synthetic data, and achieves comparable results on experimental data for a full eukaryotic genome. The code, data, and models can be accessed athttps://github.com/AI4SCR/ChromFormer.
Deciphering the maturation of tertiary lymphoid structures in cancer and inflammatory diseases of the digestive tract using imaging mass cytometry: from high-level data to a simple architectural and functional grading
Authors: Le Rochais Marion , Hémon Patrice , Ben-guigui Danivanh , Garaud Soizic , Le Dantec Christelle , Pers Jacques-Olivier , Uguen Arnaud
Published: November 2022

Objective

Persistent inflammation can promote the development of tertiary lymphoid structures (TLS) within tissues resembling the secondary lymphoid organs (SLO) as lymph nodes (LN). The composition of the TLS across different organs and diseases could be of pathophysiological and medical interest. In this work, we compared TLS to SLO and between cancer and inflammatory diseases of the digestive tract.

Design

Colorectal and gastric tissues with different inflammatory diseases and cancers from the department of pathology of CHU Brest were analyzed based on 39 markers using imaging mass cytometry (IMC). Unsupervised and supervised clustering analyses of IMC images were used to compare SLO and TLS.

Results

Unsupervised analyses tended to group TLS per patient but not per disease. Supervised analyses of IMC images revealed that LN had a more organized structure than TLS and non-encapsulated SLO Peyer’s patches. TLS followed a maturation spectrum with close correlations between germinal cell (GC) markers’ evolution. The correlations between organizational and functional markers made relevant the previously proposed TLS division into three stages: lymphoid-aggregates (LA) (CD20+CD21-CD23-) had neither organization nor GC functionality, non-GC TLS (CD20+CD21+CD23-) were organized but lacked GC’s functionality and GC-like TLS (CD20+CD21+CD23+) had GC’s organization and functionality. This architectural and functional maturation grading of TLS pointed to differences across diseases.

Conclusion

TLS architectural and functional maturation grading is accessible with few markers allowing future diagnostic, prognostic, and predictive studies on the value of TLS grading, quantification and location within pathological tissues in cancers and inflammatory diseases.

KEY MESSAGES

-What is already known on this topic:Tertiary lymphoid structures (TLS) arise in organs under various pathological conditions and can be of prognostic significance.

-What this study adds:This study deciphers the composition of TLS in digestive cancers and inflammatory diseases using massively multiplexed (39 markers) imaging mass cytometry (IMC). Beyond the term TLS, this study points to the heterogeneity of these structures in terms of composition and maturation but also the relevance of a simple architectural and functional three-stage grading of TLS.

-How this study might affect research, practice, or policy:This preliminary study paves the way for future studies evaluating the diagnostic, prognostic and theranostic values of TLS maturation grading, quantification and location within tissues as novel biomarkers in inflammatory diseases and cancers.
HeatChips: A versatile, low-cost and microscopy-compatible heating system for microfluidic devices
Authors: Aspert Théo , Charvin Gilles
Published: November 2022

Microfluidic systems are widely used in biology for their ability to control environmental parameters. Specifically, cell culture or chemistry in microfluidic devices requires tight control of the temperature. In addition, microfluidic devices can be made transparent to visible light and compatible with inverted microscopes. Yet, the current temperature control systems that allow high-resolution microscopy either require a set of complex secondary channels, a bulky, expensive, and microscope-dependent incubator, or fail to produce a homogenous temperature profile across the sample area. Here, we present HeatChips, a simple, cost-effective system to heat samples inside PDMS-based microfluidic devices in a homogeneous manner. It is based on a transparent heating glass in contact with the top of the microfluidic device, and a contactless, infrared temperature sensor attached to the objective that directly reads the temperature of the bottom of the chip. This portable system is compatible with most chip designs and allows imaging of the sample on inverted microscopes for extended periods of time without any optical restriction, for a cost of less than 100€.

Specifications table
Snapper: a high-sensitive algorithm to detect methylation motifs based on Oxford Nanopore reads
Authors: Konanov Dmitry N. , Babenko Vladislav V. , Belova Aleksandra M. , Madan Arina G. , Boldyreva Daria I. , Glushchenko Oksana E. , Butenko Ivan O. , Fedorov Dmitry E. , Manolov Aleksandr I. , Lazarev Vassili N. , Govorun Vadim M. , Ilina Elena N.
Published: November 2022

The Oxford Nanopore technology has a great potential for the analysis of genome methylation, including full-genome methylome profiling. However, there are certain issues while identifying methylation motif sequences caused by low sensitivity of the currently available motif enrichment algorithms. Here, we present Snapper, a new highly-sensitive approach to extract methylation motif sequences based on a greedy motif selection algorithm. Snapper has shown higher enrichment sensitivity compared with the MEME tool coupled with Tombo or Nanodisco instruments, which was demonstrated onH. pyloristrain J99 studied earlier using the PacBio technology. In addition, we used Snapper to characterize the total methylome of a newH.pyloristrain A45. The analysis revealed the presence of at least 4 methylation sites that have not been described forH. pyloriearlier. We experimentally confirmed a new CCAG-specific methyltransferase and indirectly inferred a new CCAAK-specific methyltransferase.
Characterizing the landscape of gene expression variance in humans
Authors: Wolf Scott , Melo Diogo , Garske Kristina M. , Pallares Luisa F. , Lea Amanda J. , Ayroles Julien F.
Published: November 2022

Gene expression variance has been linked to organismal function and fitness but remains a commonly ne-glected aspect of molecular research. As a result, we lack a comprehensive understanding of the patterns of transcriptional variance across genes, and how this variance is linked to context-specific gene regulation and gene function. Here, we use 57 large publicly available RNA-seq data sets to investigate the landscape of gene expression variance. These studies cover a wide range of tissues and allowed us to assess if there are consistently more or less variable genes across tissues and data sets and what mechanisms drive these patterns. We show that gene expression variance is broadly similar across tissues and studies, indicating that the pattern of transcriptional variance is consistent. We use this similarity to create both global and within-tissue rankings of variation, which we use to show that function, sequence variation, and gene regulatory signatures contribute to gene expression variance. Low-variance genes are associated with fundamental cell processes and have lower levels of genetic polymorphisms, have higher gene-gene connectivity, and tend to be associated with chromatin states associated with transcription. In contrast, high-variance genes are enriched for genes involved in immune response, environmentally responsive genes, immediate early genes, and are associated with higher levels of polymorphisms. These results show that the pattern of transcriptional variance is not noise. Instead, it is a consistent gene trait that seems to be functionally constrained in human populations. Furthermore, this commonly neglected aspect of molecular phenotypic variation harbors important information to understand complex traits and disease.

Author Summary

Gene expression variance, or the variation in the level of gene expression within a population, can have significant impacts on physiology, disease, and evolutionary adaptations. While the average level of gene expression is typically the focus of research, the variation around this average level (i.e., gene expression variance) can also be important for understanding complex traits and disease. Here, we investigate the landscape of transcriptional variance across tissues, populations, and studies. Using large publicly available RNA-seq data sets, we were able to identify the general properties associated with high- and low-variance genes, as well as factors driving variation in variance across genes. Specifically, we uncovered gene expression variance was significantly associated with gene length, nucleotide diversity, the degree of connectivity and the presence of non-coding RNA. Our results suggest that the mechanisms responsible for maintaining optimal levels of variation in high-versus low-variance differ, and that this variability is the result of different patterns of selection.
Bidirectional epigenetic editing reveals hierarchies in gene regulation
Authors: Pacalin Naomi M. , Shi Quanming , Parker Kevin R. , Chang Howard Y.
Published: November 2022

CRISPR perturbations are valuable tools for studying the functional effects of the genome. However, existing methods are limited in their utility for studying noncoding elements and genetic interactions. Here, we develop a system for bidirectional epigenetic editing (CRISPRai), in which orthogonal activating (CRISPRa) and repressive (CRISPRi) perturbations are applied simultaneously to multiple loci the same cell. We developed dual-gRNA-capture single-cell Perturb-seq to study the established interaction between SPI1 and GATA1, two hemopoietic lineage transcription factors, and discovered novel context-specific regulation modes for co-regulated genes. Extending CRISPRai to noncoding elements, we addressed how multiple enhancers interact to modulate expression of a shared target gene, Interleukin-2, in T cells. We found that enhancer function was primarily additive and enabled fine-tuning of gene expression, yet a clear hierarchy existed among enhancers in strength of gene expression control. The promoter was dominant over most enhancers in controlling gene expression; however, a small subset of enhancers exhibited strong functional effects, or gatekeeper function, and could turn off the gene despite promoter activation. Integration of these functional data with histone ChIP-seq and TF motif enrichment suggests the existence of multiple modes of enhancer-mediated gene regulation. Our method, CRISPRai for bidirectional epigenetic editing, provides an approach for identifying novel genetic interactions that may be overlooked when studied without bidirectional perturbations and can be applied to both genes and noncoding elements.
Defining the Parameters to Improve Plant Regeneration with Developmental Regulators
Authors: Nasti Ryan , Cody Jon P. , Zinselmeier Matt H. , Badey Nikil B. , Sridhar Adhvaith , Sharma Ambika , Maher Michael F. , Blackman Benjamin K. , Voytas Daniel F.
Published: November 2022

Tissue culture methods which serve as the standard to regenerate modified plants are challenging and have limited the capacity to engineer new accessions. To improve upon these techniques, genome modifying reagents have been combined with developmental regulators to create gene edited plant tissues in both monocot and eudicot species. Co-culturing seedlings with Agrobacterium strains encoding developmental regulatory genes has proved to be effective at producingde novomeristems in multiple eudicot species. In order to see that this technology scales well beyond proof of concept experiments, various parameters were tested for refinement. Improvements have been observed at the key stages of growth induction and progression to shooting by manipulating the vector design, developmental regulator choice, Agrobacterium strain selection, and regulatory gene removal systems. Having defined these parameters as viable optimization points, the avenues to apply developmental regulators for plant regeneration in more diverse species have become more feasible.
A Framework for Better Sensor-Based Beehive Health Monitoring
Authors: Zaman Asaduz , Dorin Alan
Published: November 2022

Hive bees provide essential pollination services to human agriculture. Managed honey bees in particular pollinate many crops, but also create honey and other bee products that are now of global economic importance. Key aspects of honey bee behaviour can be understood by observing hives. Hence, the limitations of manual observation are increasingly being addressed by new technologies that automate and extend the reach of hive monitoring.

Here we propose a framework to classify and clarify the potential for sensor-assisted hive monitoring to inform apiculture and, ultimately, improve hive bee management. This framework considers hive monitoring approaches across three newly proposed categories: Operational monitoring, Investigative monitoring, and Predictive monitoring. These categories constitute a new “OIP Framework” of hive monitoring. Each category has its own requirements for underlying technology that includes sensors and ICT resources we outline. Each category is associated with particular outcomes and benefits for apiculture and hive health monitoring detailed here. Application of these three classes of sensor-assisted hive monitoring can simplify understanding and improve best-practice management of hive bees.

Our survey and classification of hive monitoring to date show that it is seldom practiced beyond honey bees, despite the need to understand bumble bees and stingless bees also. Perhaps unsurprisingly, sensor-based hive monitoring is shown to remain primarily a practice of developed nations. Yet we show how all countries, especially developing nations, stand to gain substantially from the benefits improved sensor-based hive monitoring offers. These include a better understanding of environmental change, an increased ability to manage pollination, an ability to respond rapidly to hive health issues such as pests and pathogens, and even an ability to react quickly to the danger posed to insects and humans alike by extreme events such as floods and fires. Finally, we anticipate that the future of hive monitoring lies in the application of Predictive monitoring, such that a hive’s anticipated future state can be preemptively managed by beekeepers working iteratively with novel hive monitoring technologies.
The neuropeptide FLP-17 regulates an oviposition behavior in the nematodeCaenorhabditis elegansthat increases maternal reproductive fitness in low oxygen environments
Authors: Lee Tong Young , Chang Eunha , Yoon Kyoung-hye , Lee Jin I.
Published: November 2022

The ability for animals to adapt their behaviors to specific environments is imperative to increase their evolutionary success. This is particularly true for behaviors such as parental behaviors that directly affect reproductive fitness. Here, we identified an oviposition behavior in the nematodeC. elegansthat increases the survival of the young. In standard laboratory culture, the bacterivorous hermaphrodite mothers lay eggs across a 2DE. colilawn with no discernable pattern. However, in 3D culture they display a stereotypical behavior in which they temporarily leave the bacteria to lay eggs far away from theE. colicolony, resulting in a scattered ring of eggs located outside the bacteria. This oviposition behavior requires low oxygen levels and is regulated by the neuropeptide FLP-17 and its cognate receptor EGL-6. We confirm that a circuitry involving the oxygen-sensing BAG neurons and the vulva muscle-controlling HSN motor neurons regulates oviposition behavior. We show that loss of proper oviposition behavior results in lower reproductive fitness for the mothers and embryonic lethality for the eggs laid in bacteria under hypoxic conditions. Finally, we show that the degree of oviposition behavior varies among wild strains ofC. elegansfound in nature. The ability forC. elegansmothers to sense their environments and adjust their behaviors in adverse conditions is likely an adaptation that has allowed the worm to thrive in diverse and often hazardous habitats.
Endothelial Caveolin-1 and CXCL10 promote transcellular migration of autoreactive T cells across the blood-brain barrier
Authors: Trevino Troy N. , Almousawi Ali A. , Ochoa-Raya Andrea , Zemanski Kait , Oliveira Suellen DS , Marottoli Felecia M. , Tai Leon M. , Minshall Richard D. , Lutz Sarah E.
Published: November 2022

CXCL10 is an interferon-inducible chemokine that can recruit CXCR3+leukocytes to the central nervous system, leading to neuroinflammation, demyelination, and neuronal losses. How CXCL10 promotes leukocyte extravasation and diapedesis across the blood-brain barrier – formed by brain endothelial cells – is poorly understood. Here, we report that CXCL10 mediates CD4+ T cell migration through the brain endothelial cell cytoplasm (transcellular), but not cell-cell junctions (paracellular), via the vesicular trafficking protein Caveolin-1. Caveolin-1 promotes CXCL10 aggregation into cytoplasmic stores in brain endothelial cellsin vitroto provide the local, high concentration necessary for recruitment of CXCR3+ leukocytes. This process also requires LFA-1 activity. In the absence of Caveolin-1, endothelial CXCL10 is secreted, and the local signaling cues are lost. Consistent with ourin vitrodata, genetic ablation of Caveolin-1 in endothelial cells reduces the severity of active experimental autoimmune encephalomyelitis (EAE), a murine model for multiple sclerosis, by decreasing the infiltration of CXCR3+ T cells into the CNS. Moreover, loss of Caveolin-1 protects against the adoptive transfer of autoreactive T cells. Our findings establish a novel mechanism by which brain endothelial cells utilize Caveolin-1 dependent CXCL10 intracellular stores to license T cells for transcellular migration across the blood-brain barrier.
Flow-induced mechanical coupling between perinuclear actin cap and nucleus governs spatiotemporal regulation of YAP transport
Authors: Ma Tianxiang , Liu Xiao , Su Haoran , He Yuan , Wu Fan , Gao Chenxing , Li Kexin , Liang Zhuqing , Zhang Dongrui , Zhang Xing , Hu Ke , Li Shangyu , Wang Li , Wang Min , Yue Shuhua , Hong Weili , Chen Xun , Zhang Jing , Deng Xiaoyan , Wang Pu , Fan Yubo
Published: November 2022

Mechanical forces, including flow shear stress, regulate fundamental cellular process by modulating the nucleocytoplasmic transport of transcription factors, such as Yes-associated Protein (YAP). However, the mechanical mechanism how flow induces the nucleocytoplasmic transport remains largely unclear. Here we found that unidirectional flow applied to endothelial cells induces biphasic YAP nucleocytoplasmic transport with initial nuclear import, followed by nuclear export as perinuclear actin cap forms and nuclear stiffening in a dose and timing-dependent manner. In contrast, pathological oscillatory flow induces slight actin cap formation and nuclear softening, sustaining YAP nuclear localization. To explain the disparately spatiotemporal distribution of YAP, we developed a three-dimensional mechanochemical model considering coupling processes of flow sensing, cytoskeleton organization, nucleus mechanotransduction, and YAP spatiotemporal transport. We discovered that actin cap formation and nuclear stiffness alteration under flow synergically regulate nuclear deformation, hence governing YAP transport. Furthermore, we expanded our single cell model to a collective vertex framework and found that actin cap irregularities in individual cells under flow shear stress potentially induce topological defects and spatially heterogeneous YAP distribution in cellular monolayers. Our work unveils the unified mechanism of flow-induced nucleocytoplasmic transport, offering a universal linkage between transcriptional regulation and mechanical stimulation.
Molecular epidemiology of Infectious Spleen and Kidney Necrosis Virus (ISKNV) in Ghanaian cultured tilapia
Authors: Ayiku Angela Naa Amerley , Adelani Abigail Akosua , Appenteng Patrick , Nkansah Mary , Ngoi Joyce M. , Morang’a Collins Misita , Paley Richard , Cudjoe Kofitsyo S. , Verner-Jeffreys David , Quashie Peter Kojo , Duodu Samuel
Published: November 2022

1

Infectious Spleen and Kidney Necrosis Virus (ISKNV) is increasingly gaining more attention globally, due to its highly significant economic impact on the aquaculture industry. In late 2018, unusually high levels of mortality (60-90%) was reported in some intensive tilapia cage culture systems in Ghana. Preliminary investigations confirmed the involvement of ISKNV, a viral pathogen noted for fatal systemic infections in many fish species. As a follow-up on the outbreak situation, and post-mass vaccination of affected fish farms, the need to investigate further the molecular epidemiology and phylogeography of the virus across Lake Volta became paramount. In this study, a multiplexed PCR assay and MinION™ nanopore sequencing of the Major Capsid Protein (MCP) were performed to investigate the presence and genotype of ISKNV in tilapia collected from 30 randomly selected farms spread across Lake Volta. Fish with and without clinical signs were included in the molecular detection of the virus from brain, kidney and spleen tissues. ISKNV was detected at 80% prevalence with fry and juvenile fish being most affected. Phylogenetic analysis of the MCP revealed that all 35 isolates from 14 different farms were ISKNV genotype I with near- 100% homology to the 2018 outbreak strain. Vaccination and heat shock treatment; the main specific interventions currently employed to control the viral pathogen have not achieved much success and ISKNV remains a threat to the growth of the aquaculture industry in Ghana. The outcome of this study can be useful in improving fish health management and biosecurity policies in the aquaculture industry.
gGN: learning to represent graph nodes as low-rank Gaussian distributions
Authors: Edera Alejandro A. , Stegmayer Georgina , Milone Diego H.
Published: November 2022

Unsupervised learning of node representations from knowledge graphs is critical for numerous downstream tasks, ranging from large-scale graph analysis to measuring semantic similarity between nodes. This study presents gGN as a novel representation that defines graph nodes as Gaussian distributions. Unlike existing representations that approximate such distributions using diagonal covariance matrices, our proposal approximates them using low-rank perturbations. We demonstrate that this low-rank approximation is more expressive and better suited to represent complex asymmetric relations between nodes. In addition, we provide a computationally affordable algorithm for learning the low-rank representations in an unsupervised fashion. This learning algorithm uses a novel loss function based on the reverse Kullback-Leibler divergence and two ranking metrics whose joint minimization results in node representations that preserve not only node depths but also local and global asymmetric relationships between nodes. We assessed the representation power of the low-rank approximation with an in-depth systematic empirical study. The results show that our proposal was significantly better than the diagonal approximation for preserving graph structures. Moreover, gGN also outperformed 17 methods on the downstream task of measuring semantic similarity between graph nodes.
Particulate matter air pollution and COVID-19 infection, severity, and mortality: A systematic review
Authors: Sheppard Nicola , Carroll Matthew , Gao Caroline , Lane Tyler
Published: November 2022

Background and objective

Ecological studies indicate ambient particulate matter ≤2.5mm (PM2.5) air pollution is associated with poorer COVID-19 outcomes. However, these studies cannot account for individual heterogeneity and often have imprecise estimates of PM2.5exposure. We review evidence from studies using individual-level data to determine whether PM2.5increases risk of COVID-19 infection, severe disease, and death.

Methods

Systematic review of case-control and cohort studies, searching Medline, Embase, and WHO COVID-19 up to 30 June 2022. Study quality was evaluated using the Newcastle-Ottawa Scale. Results were pooled with a random effects meta-analysis, with Egger’s regression, funnel plots, and leave-one-out and trim-and-fill analyses to adjust for publication bias.

Results

N=18 studies met inclusion criteria. A 10μg/m3 increase in PM2.5exposure was associated with 66% (95% CI: 1.31-2.11) greater odds of COVID-19 infection (N=7) and 127% (95% CI: 1.41-3.66) increase in severe illness (hospitalisation or worse) (N=6). Pooled mortality results (N=5) were positive but non-significant (OR 1.40; 0.94 to 2.10). Most studies were rated “good” quality (14/18 studies), though there were numerous methodological issues; few used individual-level data to adjust for confounders like socioeconomic status (4/18 studies), instead using area-based indicators (12/18 studies) or not adjusting for it (3/18 studies). Most severity (9/10 studies) and mortality studies (5/6 studies) were based on people already diagnosed COVID-19, potentially introducing collider bias.

Conclusion

There is strong evidence that ambient PM2.5increases the risk of COVID-19 infection, and weaker evidence of increases in severe disease and mortality.

Funding

This review was completed as a Scholarly Intensive Placement project by NS, which received no funding.

Competing interests

The authors declare no competing interests.

Registration

This study was registered on PROSPERO on 8 July 2022 (CRD42022345129):https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022345129
The perceptual nature of illusory object recognition
Authors: Alilović Josipa , Lampers Eline , Slagter Heleen A. , van Gaal Simon
Published: November 2022

We occasionally misinterpret ambiguous sensory input or report a stimulus when none is presented. It is unknown whether such errors have a sensory origin and reflect true perceptual illusions, or whether they have a more cognitive origin (e.g., are due to guessing), or both. When participants performed an error-prone and challenging face/house discrimination task, multivariate EEG analyses revealed that during decision errors (mistaking a face for a house), sensory stages of visual information processing initially represent the presented stimulus category. Crucially however, when participants were confident in their erroneous decision, so when the illusion was strongest, this neural representation flipped later in time and reflected the incorrectly reported percept. This flip in neural pattern was absent for decisions that were made with low confidence. This work demonstrates that decision confidence arbitrates between perceptual decision errors, which reflect true illusions of perception, and cognitive decision errors, which do not.
Identification of basic helix-loop-helix transcription factors that activate betulinic acid biosynthesis by RNA-sequencing of hydroponically culturedLotus japonicus
Authors: Suzuki Hayato , Takahashi Hirokazu , Fukushima Ery Odette , Nakazono Mikio , Muranaka Toshiya , Seki Hikaru
Published: November 2022

Although triterpenes are ubiquitous in plant kingdom, their biosynthetic regulatory mechanisms are limitedly understood. Here, we found that hydroponic culture dramatically activated betulinic acid (BA) biosynthesis in the model FabaceaeLotus japonicus, and investigated its transcriptional regulation. Fabaceae plants develop secondary aerenchyma (SA) on the surface of hypocotyls and roots during flooding for root air diffusion. Hydroponic culture induced SA inL. japonicusand simultaneously increased the accumulation of BA and the transcript levels of its biosynthetic genes. RNA-sequencing of soil-grown and hydroponically cultured plant tissues, including SA collected by laser microdissection, revealed that several transcription factor genes were co-upregulated with BA biosynthetic genes. Overexpression ofLjbHLH32andLjbHLH50inL. japonicustransgenic hairy roots upregulated the expression of BA biosynthesis genes, resulting in enhanced BA accumulation. However, transient luciferase reporter assays inArabidopsismesophyll cell protoplasts showed that LjbHLH32 transactivated promoters of biosynthetic genes in the soyasaponin pathway but not the BA pathway, like its homolog GubHLH3, a soyasaponin biosynthesis regulator inGlycyrrhiza uralensis. This suggested the evolutionary origin and complex regulatory mechanisms of BA biosynthesis in Fabaceae. This study sheds light on the unrevealed biosynthetic regulatory mechanisms of triterpenes in Fabaceae plants.

Highlight

Hydroponic culture enhanced betulinic acid synthesis inLotus japonicus. RNA-sequencing and functional characterization experiments suggest that LjbHLH32 and LjbHLH50 are the transcription factors activating betulinic acid biosynthesis.