bluuebunny/crossref_metadata_2025 huggingface dataset:
Patients with rheumatoid arthritis with moderate or high disease activity benefit from multidisciplinary rehabilitation: a nested case-control study
Authors: Cunha Bernardo M , Ferreira Bruno SA , Barros Camila SM , Silva Jesiniana R , Kauer Juliana B , Moreira Larissa A , Gushikem Andreia ,   GIRE - Grupo de Investigação em REabilitação REumatológica
Published: May 2021

Background

rheumatologists recognize the importance of rehabilitation in patients with rheumatoid arthritis (RA), but they are not confident if patients with significant disease activity would benefit from it.

Objective

To verify if rheumatoid arthritis patients with moderate to severe inflammatory activity (MHA) improve functional capacity (FC) after a comprehensive rehabilitation program.

Methods

Nested case-control study. RA patients who completed a rehabilitation program between June 2014 and December 2017 were included. The interventions were prescribed according to the rehabilitation team’s discretion. FC was assessed with Health Assessment Questionnaire Disability Index (HAQ) and compared between before and after interventions. The group which improved at least 50% in CDAI was compared to the group which achieved <50%.

Results

We included 46 patients with complete HAQ and baseline CDAI data, with a mean age of 53.6 years and mean disease duration of 11.8 years. HAQ and CDAI improved on average 0.481 (± 0.500) and 14.2 (± 16.7), respectively. Patients who improved CDAI tended to have a greater mean HAQ difference (0.6 vs. 0.3; p = 0.058). Conversely, patients who did not improve disease activity had a HAQ reduction of 0.3 (± 0.4). Post-hoc analysis was performed on the group of 9 patients with baseline CDAI ≤10. A mean baseline CDAI of 5.2 and a mean HAQ difference of 0.319 (0.079; 0.56; p = 0.016) were found.

Conclusions

After rehabilitation, RA patients with sustained MHA improved FC similarly to patients with baseline mild activity or remission. Thus, patients with RA and MHA may benefit from rehabilitation concurrently with drug treatment. This study suggests that the range of improvement in FC with rehabilitation appears to have an additive effect to the drug therapy.
“The added value of 18f-FDG PET/CT in the assessment of onset and steroid resistant polimyalgia rheumatica”
Authors: Alvarado Patricia Moya , Leon Alejandro Fernandez , Corica Maria Emilia , Marti Valle Camacho , López-Mora Diego Alfonso , Castellví Barranco Ivan , Corominas Hèctor
Published: April 2021

PMR is a common inflammatory rheumatic disease. Although its clinical characteristics are fully recognized, no specific test for its diagnosis has been established to date. Several studies have described a wide variety of diseases that present with polymyalgic symptoms. A 18FDG-PET/CT scan could help to deal with these differential diagnoses. The goal of our study is to describe the findings of the 18FDG-PET/CT scan in a cohort of PMR patients and to detail how the 18FDG-PET/CT scan improves accuracy when diagnosing other underlying conditions. This cross-sectional study enrolled patients with a diagnosis of PMR who underwent to a 18FDG-PET/CT scan to rule out other diagnosis. The 18FDG-PET/CT scan was performed either following clinical criteria at the onset of clinical symptoms or when the patient became PMR steroid resistant. Patients’ demographic, clinical and analytical data at the moment of the 18FDG-PET/CT scan were recorded. The final diagnosis was confirmed according to clinical judgement. A total of 103 patients with PMR were included. In 49.51% of patients, the 18FDG-PET/CT scan was ordered to study resistance to steroid therapy. The final diagnoses of patients were PMR in 70.9% patients, large vessel vasculitis in 15.5%, neoplasms 4.8% and another diagnosis in the rest. The 18FDG-PET/CT scan is a very useful technique for the study of Polymyalgia Rheumatica, not only to help in the diagnostic process, but also due to its role in the identification of a variety of PMR-like patrons.
Antitumor activity of a lectibody targeting cancer-associated high-mannose glycans
Authors: Oh Young Jun , Dent Matthew W. , Freels Angela R. , Zhou Qingwen , Lebrilla Carlito B. , Merchant Michael L. , Matoba Nobuyuki
Published: April 2021

Aberrant protein glycosylation is a hallmark of cancer, but few drugs targeting cancer glycobiomarkers are currently available. Here, we show that a “lectibody” consisting of the high-mannose glycan-binding lectin Avaren and human IgG1 Fc (AvFc) selectively recognizes a range of cell lines derived from lung, breast, colon and blood cancers at nanomolar concentrations. AvFc’s binding to the non-small cell lung cancer (NSCLC) cell lines A549 and H460 was characterized in detail. Co-immunoprecipitation proteomics analysis revealed that epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF1R) are among the lectibody’s common targets in these cells. AvFc blocked the activation of EGFR and IGF1R by their respective ligands in A549 cells and inhibited the migration of A549 and H460 cells upon stimulation with EGF and IGF1. Furthermore, AvFc induced potent Fc-mediated cytotoxic effects and significantly retarded A549 and H460 tumor growth in SCID mice. Immunohistochemistry analysis of primary lung tissues from NSCLC patients demonstrated that AvFc preferentially binds to tumors over adjacent non-tumor tissues. Our findings provide evidence that increased abundance of high-mannose glycans in the glycocalyx of cancer cells can be a druggable target, and AvFc may provide a new tool to probe and target this tumor-associated glycobiomarker.
POPULATION-BASED SERO-EPIDEMIOLOGICAL STUDY PROTOCOL FOR THE IMPACT OF SMOKING ON SARS-COV-2 INFECTION AND COVID-19 OUTCOMES – THE TROINA STUDY
Authors: Polosa R. , Tomaselli V. , Ferrara P. , Romeo A. C. , Rust S. , Saitta D. , Caraci F. , Romano C. , Thangaraju M. , Zuccarello P. , Rose J. , Ferrante M , Belsey J. , Cibella F. , Interlandi E. , Ferri R.
Published: May 2021

After the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), research has highlighted several aspects of the pandemic, focusing on clinical features and risk factors associated with infection and disease severity. However, emerging results on the role of smoking in SARS-CoV-2 infection susceptibility or COVID-19 outcomes are conflicting, and their robustness remains uncertain. In this context, this project aims at quantifying the proportion of SARS-CoV-S antibody seroprevalence, studying the changes in antibody levels over time, and analyzing the association between smoking status and infection using seroprevalence data.

The added value of this research is that the current smoking status of the population to be studied will be biochemically verified, in order to avoid the bias associated with self-reported smoking status. As such, the results from this survey may provide actionable metric to study the role of smoking in SARS-CoV-2 spread, and therefore implement the most appropriate public health measures to control the pandemic.

The research design involves a 6-month prospective cohort study with serial sampling of the same individuals. Each participant will be surveyed about their demographics and COVID-19-related information, and blood sampling will be collected upon recruitment and at specified follow-up time points (namely, after 8 and 24 weeks). Blood samples will be screened for the presence of SARS-CoV-2 specific antibodies and serum cotinine.

Overall, we expect to find a higher prevalence of antibodies in individuals at high-risk for viral exposure (i.e., healthcare or other essential workers), according to previous literature, and to refine current estimates on the association between smoking status and SARS-CoV-2/COVID-19. Our results may serve as a reference for future clinical research and the methodology could be exploited in public health sectors and policies.
The validation of a mobile sensor-based neurobehavioral assessment with machine learning analytics
Authors: Sloane Kelly L. , Glenn Shenly , Mefford Joel A. , Zhao Zilong , Xu Man , Zhou Guifeng , Mace Rachel , Wright Amy E , Hillis Argye E.
Published: May 2021

Background

Mild cognitive impairment is a common yet complex condition that is often underdiagnosed in the early stages. Miro Health is a mobile platform for the self-administration of sensor-based cognitive and behavioral assessments that was developed to measure factors typical of legacy neuropsychological tests in addition to behaviors that are currently left to subjective clinical impression such as eye movement, language, and processing speed.

Objective

Studies were conducted to measure Miro Health’s concurrent validity, test-retest reliability, and amnestic MCI classification performance.

Method

Spearman correlations were calculated to estimate the concurrent validity of Miro Health variables with legacy neuropsychological test variables using data from 160 study participants. Fifty-nine healthy controls were assessed at three time points to evaluate the test-retest reliability of Miro Health scores. Reliability was quantified with the scores’ intraclass correlations. Learning effects were measured as trends. In addition, a machine learning algorithm combined Miro Health variable scores into a Risk Score designed to distinguish 65 healthy controls (HC), 38 MCI participants (21 amnestic MCI (aMCI), and 17 non-amnestic MCI (naMCI)).

Results

Significant correlations of Miro Health variables with legacy neuropsychological test variables were observed. Longitudinal studies show agreement of subsequent measurements and minimal learning effects. The Risk Score distinguished aMCI from healthy controls with an Area Under the Receiver Operator Curve (AUROC) of 0.97; the naMCI participants and controls were separated with an AUROC of 0.80, and the combined MCI group (aMCI + naMCI) was separated from healthy controls with an AUROC of 0.89.

Conclusion

Miro Health includes valid and reliable versions of variable scores that are analogous to legacy neuropsychological variable scores and a machine-learning derived risk score that effectively distinguishes HCs and individuals with MCI.
An 8-DNA methylation signature predicts recurrence risk of cervical cancer
Authors: Ma Jing-Hang , Huang Yu , Liu Lu-Yao , Feng Zhen
Published: April 2021

Purpose

Cervical cancer is the leading cause of cancer-associated mortalities in female worldwide. DNA methylation have been demonstrated to have a regulatory role in the progression and could be novel biomarkers to predict the recurrence of the disease.

Methods

DNA methylation and RNA expression data of cervical cancer were downloaded from TCGA. DMGs and DEGs were screened and extracted by correlation analysis. The SVM-based recurrence prediction model was established using the selected DMGs. Cox regression analysis and ROC analysis were used as self-evaluations. The GEO database was applied for external validation. Functional enrichment was determined by GO and KEGG analysis.

Results

The eight-DNA methylation signature could identify patients with a high risk of recurrence (AUC=0.833). The SVM score was an independent risk factor for recurrence (HR = 0.418; 95% CI: 0.26-0.67, p-value <0.05). The independent GEO database further supported the result.

Conclusion

The predictive function of the 8-DNA methylation signature for recurrence of cervical cancer was revealed in this study, which may help identify high-risk patients of recurrence and benefit the clinical treatment.
Modelling digital and manual contact tracing for COVID-19 Are low uptakes and missed contacts deal-breakers?
Authors: Rusu Andrei , Farrahi Katayoun , Emonet Rémi
Published: May 2021

Comprehensive testing schemes, followed by adequate contact tracing and isolation, represent the best public health interventions we can employ to reduce the impact of an ongoing epidemic when no or limited vaccines are available and the implications of a full lockdown are to be avoided. However, the process of tracing can prove feckless for highly-contagious viruses such as SARS-Cov-2. The interview-based approaches often miss contacts and involve significant delays, while digital solutions can suffer from insufficient adoption rates or inadequate usage patterns. Here we present a novel way of modelling different contact tracing strategies using a generalizedmulti-site mean-fieldmodel, which can naturally assess the impact of both manual and digital approaches. Our methodology can readily be applied to any compartmental formulation, thus enabling the study of several complex pathogens. We use this technique to simulate a new epidemiological model, SEIR-T, and show that, given the right conditions, tracing in a COVID-19 epidemic can be effective even when digital uptakes are sub-optimal or interviewers miss a fair proportion of the contacts.
An Aerobic Anoxygenic Phototrophic Bacterium Fixes CO2via the Calvin-Benson-Bassham Cycle
Authors: Tang Kai , Liu Yang , Zeng Yonghui , Feng Fuying , Jin Ke , Yuan Bo
Published: April 2021

Aerobic anoxygenic phototrophic bacteria (AAnPB) are photoheterotrophs, which use light as auxiliary energy and require organic carbon (OC) for growth. Herein, we report the unusual strain B3, which is a true AAnPB because it requires oxygen for growth, harbours genes forcbb3- andbd-type cytochromes andacsF, and produces bacteriochlorophyll. The B3 genome encodes the complete metabolic pathways for AAnPB light utilization, CO2fixation via Calvin-Benson-Bassham (CBB) cycle and oxidation of sulfite and H2, and the transcriptome indicated that all components of these pathways were fully transcribed. Expression of the marker genes related to photosynthesis, includingpufM for light harnessing andrbcL for CO2fixation, and the activity of RubisCO, the key enzyme in the Calvin-Benson-Bassham (CBB) cycle, increased in response to decreased OC supply. Large amounts of cell biomass were obtained in liquid BG11 medium under illumination. The strain thus likely photoautotrophically grows using sulfite or H2as an electron donor. Similar GC contents between photosynthesis, the CBB cycle and 16S rRNA genes and the consistency of their phylogenetic topologies implied that light harnessing and carbon fixation genes evolved vertically from an anaerobic phototrophic ancestor of Rhodospirillaceae in Alphaproteobacteria. In conclusion, strain B3 represents a novel AAnPB characterized by photoautotrophy using the CBB cycle. This kind of AAnPB may be ecologically significant in the global carbon cycle.
The predictive potential of key adaptation parameters and proxy fitness traits between benign and stressful thermal environments
Authors: Cocciardi Jennifer M. , O’Brien Eleanor K. , Hoskin Conrad J. , Stoetzel Henry , Higgie Megan
Published: April 2021

Understanding the adaptive potential of a species is key when predicting whether a species can contend with climate change. Adaptive capacity depends on the amount of genetic variation within a population for relevant traits. However, genetic variation changes in different environments, making it difficult to predict whether a trait will respond to selection when not measured directly in that environment. Here, we investigated how genetic variances, and phenotypic and genetic covariances, between a fitness trait and morphological traits changed between thermal environments in two closely-relatedDrosophila. If morphological traits strongly correlate with fitness, they may provide an easy-to-measure proxy of fitness to aid in understanding adaptation potential. We used a parent-offspring quantitative genetic design to test the effect of a benign (23°C) and stressful (28°C) thermal environment on genetic variances of fecundity and wing size and shape, and their phenotypic and genetic covariances. We found genetic variances were higher within the stressful environment for fecundity but lower within the stressful environment for wing size. We did not find evidence for significant phenotypic correlations. Phenotypic and genetic correlations did not reveal a consistent pattern between thermal environmentsorwithin or between species. This corroborates previous research and reiterates that conclusions drawn in one environment about the adaptive potential of a trait, and the relationship of that trait with fitness, cannot be extrapolated to other environmentsorwithin or between closely-related species. This confirms that researchers should use caution when generalising findings across environments in terms of genetic variation and adaptive potential.
Mapping vestibular and visual contributions to angular head velocity tuning in the cortex
Authors: Hennestad Eivind , Witoelar Aree , Chambers Anna , Vervaeke Koen
Published: April 2021

Neurons that signal the direction and angular velocity of head movements (AHV cells) are critically important to process visual and spatial information. However, it has been challenging to isolate the sensory modality that drives them and to compre hensively map their cortical distribution. To address this, we developed a method that enables rotating awake, head-fixed mice under a two-photon microscope in a visual environment. Starting in layer 2/3 of the retrosplenial cortex, a key area for vision and navigation, we found that a significant fraction of rotation sensitive neurons report AHV. These tuning properties depend on vestibular input because they persist in darkness and are reduced when replaying visual flow to stationary animals. When mapping the spatial extent, we found AHV cells in all cortical areas that we explored, including motor, somatosensory, visual and posterior parietal cortex. Notably, the vestibular and visual contributions to AHV are area dependent. Thus, many cortical circuits have access to AHV, enabling a diverse integration with sensorimotor and cognitive information.
The molecular structure and surface accumulation dynamics of hyaluronan at the water/air interface
Authors: Moll Carolyn J. , Giubertoni Giulia , Versluis Jan , Koenderink Gijsje H. , Bakker Huib J.
Published: April 2021

Hyaluronan is a biopolymer that is essential for many biological processes in the human body, like the regulation of tissue lubrication and inflammatory responses. Here we study the behavior of hyaluronan at aqueous surfaces using heterodyne-detected vibrational sum-frequency generation spectroscopy (HD-VSFG). We find that high-molecular weight hyaluronan (>1 MDa) does not come to the surface, even hours after addition of the polymer to the aqueous solution. In contrast, low-molecular weight hyaluronan (~150 kDa) gradually covers the water-air interface within hours, leading to a negatively charged surface and a reorientation of the interfacial water molecules. This strong dependence on the polymer molecular weight can be explainend from entanglements of the hyaluronan polymers. We also find that the migration kinetics of hyaluronan in aqueous media shows an anomalous dependence on the pH of the solution, which can be explained from the interplay of hydrogen-bonding and electrostatic interactions of the hyaluronan polymers.
Increased signal to noise ratios within experimental field trials by regressing spatially distributed soil properties as principal components
Authors: Berry Jeffrey C. , Qi Mingsheng , Sonawane Balasaheb V. , Sheflin Amy , Cousins Asaph B. , Prenni Jessica , Schachtman Daniel P. , Liu Peng , Bart Rebecca S.
Published: April 2021

Environmental variability poses a major challenge to any field study. Researchers attempt to mitigate this challenge through replication. Thus, the ability to detect experimental signals is determined by the degree of replication and the amount of environmental variation, noise, within the experimental system. A major source of noise in field studies comes from the natural heterogeneity of soil properties which create micro-treatments throughout the field. To make matters worse, the variation within different soil properties is often non-randomly distributed across a field. We explore this challenge through a sorghum field trial dataset with accompanying plant, microbiome and soil property data. Diverse sorghum genotypes and two watering regimes were applied in a split-plot design. We describe a process of identifying, estimating, and controlling for the effects of spatially distributed soil properties on plant traits and microbial communities using minimal degrees of freedom. Importantly, this process provides a tool with which sources of environmental variation in field data can be identified and removed, improving our ability to resolve effects of interest and to quantify subtle phenotypes.

IMPORTANCE

Data from field experiments are notoriously noisy. Proper field designs with high replication aid in mitigating this challenge, yet true biological correlations are still often masked by environmental variability. This work identifies soil property composition as a spatially distributed source of variance to three types of characteristics: plant phenotype, microbiome composition, and leaf traits. We show that once identified, spatial principal component regression was able to account for these effects so that more precise estimates of experimental factors were obtained. This generalizable method is applicable to diverse field experiments.
Nucleosome induced homology recognition in chromatin
Authors: Hedley Jonathan G. , Teif Vladimir B. , Kornyshev Alexei A.
Published: April 2021

One of the least understood properties of chromatin is the ability of its similar regions to recognise each other through weak interactions. Theories based on electrostatic interactions between helical macromolecules suggest that the ability to recognize sequence homology is an innate property of the non-ideal helical structure of DNA. However, this theory does not account for nucleosomal packing of DNA. Can homologous DNA sequences recognize each other while wrapped up in the nucleosomes? Can structural homology arise at the level of nucleosome arrays? Here we present a theoretical investigation of the recognition-potential-well between chromatin fibers sliding against each other. This well is different to the one predicted and observed for bare DNA; the minima in energy do not correspond to literal juxtaposition, but are shifted by approximately half the nucleosome repeat length. The presence of this potential-well suggests that nucleosome positioning may induce mutual sequence recognition between chromatin fibers and facilitate formation of chromatin nanodomains. This has implications for nucleosome arrays enclosed between CTCF-cohesin boundaries, which may form stiffer stem-like structures instead of flexible entropically favourable loops. We also consider switches between chromatin states, e.g., through acetylation/deacetylation of histones, and discuss nucleosome-induced recognition as a precursory stage of genetic recombination.
Reconstitution of prenyltransferase activity on nanodiscs by components of the rubber synthesis machinery of the Para rubber tree and guayule
Authors: Kuroiwa Fu , Nishino Akira , Mandal Yasuko , Suenaga-Hiromori Miki , Suzuki Kakeru , Takani Yukie , Miyagi-Inoue Yukino , Yamaguchi Haruhiko , Yamashita Satoshi , Takahashi Seiji , Tozawa Yuzuru
Published: April 2021

Prenyltransferases mediate the biosynthesis of various types of polyisoprene compound in living organisms. Natural rubber (NR) of the Para rubber tree (Hevea brasiliensis) is synthesized as a result of prenyltransferase activity, with the proteins HRT1, HRT2, and HRBP having been identified as candidate components of the rubber biosynthetic machinery. To clarify the contribution of these proteins to prenyltransferase activity, we established a cell-free translation system for nanodisc-based protein reconstitution and measured the enzyme activity of the protein-nanodisc complexes. Cell-free synthesis of HRT1, HRT2, and HRBP in the presence of asolectin nanodiscs revealed that all three proteins were membrane associated. A complex of HRT1 and HRBP formed as a result of co-expression of the two proteins in the presence of nanodiscs manifested marked polyisoprene synthesis activity, whereas neither HRT1, HRT2, or HRBP alone nor a complex of HRT2 and HRBP exhibited such activity. Similar analysis of guayule (Parthenium argentatum) proteins revealed that three HRT1 homologs (CPT1–3) manifested prenyltransferease activity only if co-expressed with the homolog of HRBP (CBP). Our results thus indicate that the core prenyltransferase of the rubber biosynthetic machinery of both the Para rubber tree and guayule is formed by the assembly of heterologous subunits (HRT1 and HRBP in the former species).
Tissue-specific metabolic reprogramming during wound inducedde novoorgan formation in tomato hypocotyl explants
Authors: Larriba Eduardo , García Ana Belén Sánchez , Martínez-Andújar Cristina , Albacete Alfonso , Pérez-Pérez José Manuel
Published: April 2021

Plants have remarkable regenerative capacity, which allows them to survive tissue damaging after biotic and abiotic stress. Some of the key transcription factors and the hormone crosstalk involved in wound-induced organ regeneration have been extensively studied in the model plantArabidopsis thaliana. However, little is known about the role of metabolism in wound-induced organ regeneration.

Here, we performed detailed transcriptome analysis and targeted metabolomics approach duringde novoorgan formation in tomato hypocotyl explants and found tissue-specific metabolic differences and divergent developmental pathways after wounding.

Our results indicate that callus growth in the apical region of the hypocotyl depends on a specific metabolic switch involving the upregulation of the photorespiratory pathway and the differential regulation of photosynthesis-related genes and of the gluconeogenesis pathway.

The endogenous pattern of ROS accumulation in the apical and basal region of the hypocotyl during the time-course were dynamically regulated, and contributed to tissue-specific wound-induced regeneration.

Our findings provide a useful resource for further investigation on the molecular mechanisms involved in wound-induced organ formation in a crop species such as tomato.

One-sentence Summary

Metabolic switch during wound-induced regeneration
Gonococcal invasion into epithelial cells depends on both cell polarity and ezrin
Authors: Yu Qian , Wang Liang-Chun , Stein Daniel C. , Song Wenxia
Published: April 2021

Neisseria gonorrhoeae(GC) establishes symptomatic infection in women from the cervix, lined with heterogeneous epithelial cells from non-polarized stratified at the ectocervix to polarized columnar at the endocervix. We have previously shown that GC differentially colonize and transmigrate across the ecto and endocervical epithelia. However, whether and how GC invade into heterogeneous cervical epithelial cells is unknown. This study examined GC entry of epithelial cells with various properties, using human cervical tissue explant and non-polarized/polarized epithelial cell line models. While adhering to non-polarized and polarized epithelial cells at similar levels, GC invaded into non-polarized more efficiently than polarized epithelial cells. The enhanced GC invasion in non-polarized epithelial cells was associated with increased ezrin phosphorylation, F-actin and ezrin recruitment to GC adherent sites, and the elongation of GC-associated microvilli. Inhibition of ezrin phosphorylation inhibited F-actin and ezrin recruitment and microvilli elongation, leading to a reduction in GC invasion. The reduced GC invasion in polarized epithelial cells was associated with non-muscle myosin II-mediated F-actin disassembly and microvilli ablation at GC adherence sites. Surprisingly, intraepithelial GC were only detected inside epithelial cells shed from the cervix, but neither in the ectocervix nor the endocervix, by immunofluorescence microscopy. We observed similar ezrin and F-actin recruitment in exfoliated cervical epithelial cells but not in those that remained in the ectocervical epithelium, as the luminal layer of ectocervical epithelial cells expressed ten-fold lower levels of ezrin than those beneath. However, GC inoculation induced F-actin reduction and myosin recruitment in the endocervix, similar to what was seen in polarized epithelial cells. Thus, polarized expression of ezrin at the apical surface of epithelial cells inhibits GC invasion, while non-polarized expression of ezrin promotes GC invasion by driving actin accumulation and microvilli elongation.
Can Hypnotic Susceptibility be Explained by Bifactor Models? Structural Equation Modeling of the Harvard Group Scale of Hypnotic Susceptibility - Form A
Authors: Zahedi Anoushiravan , Sommer Werner
Published: April 2021

Individuals differ in their responsiveness to hypnotic suggestions. However, defining and measuring hypnotizability is contentious because standardized scales, such as the Harvard group scale (HGSHS:A), measure a mixture of general suggestibility and its alteration due to hypnotic induction (hypnotizability). Exploratory factor analyses (FA) of standardized scales indicated their multidimensionality; however, the number and nature of latent factors are debated. We applied Confirmatory FA to the HGSHS:A scores of 477 volunteers and tested several theory-driven models. Scores were best explained by a bifactor model consisting of a G-factor and three correlated minor factors. The presented bifactor model shows that two sources of variability affect HGSHS:A simultaneously. Structural equation modeling revealed that the challenge-ideomotor factor predicts the other two minor factors, implying these suggestions might require more fundamental processes than other types. These results demonstrate the multifaceted and bifactorial structure of hypnotic suggestibility and underscore the desideratum for developing more differentiated scales.
Testing covariance models for MEG source reconstruction of hippocampal activity
Authors: O’Neill George C. , Barry Daniel N. , Tierney Tim M. , Mellor Stephanie , Maguire Eleanor A. , Barnes Gareth R.
Published: April 2021

Beamforming is one of the most commonly used source reconstruction methods for magneto- and electroencephalography (M/EEG). One underlying assumption, however, is that distant sources are uncorrelated and here we tested whether this is an appropriate model for the human hippocampal data. We revised the Empirical Bayesian Beamfomer (EBB) to accommodate specific a-priori correlated source models. We showed in simulation that we could use model evidence (as approximated by Free Energy) to distinguish between different correlated and uncorrelated source scenarios. Using group MEG data in which the participants performed a hippocampal-dependent task, we explored the possibility that the hippocampus or the cortex or both were correlated in their activity across hemispheres. We found that incorporating a correlated hippocampal source model significantly improved model evidence. Our findings help to explain why, up until now, the majority of MEG-reported hippocampal activity (typically making use of beamformers) has been estimated as unilateral.
“Age-related declines in neural selectivity manifest differentially during encoding and recognition”
Authors: Pauley Claire , Sommer Verena R. , Kobelt Malte , Keresztes Attila , Werkle-Bergner Markus , Sander Myriam C.
Published: April 2021

The authors have withdrawn the preprint due to two errors in the analyses: The first error was a failure to account for three dummy volumes (TR = 2s) collected at the beginning of each experimental run. The second error was a coding error related to the definition of the category-selective clusters. Since correcting for these errors drastically altered the results and conclusions of this paper, the authors have withdrawn the preprint and retracted the published paper (https://doi.org/10.1016/j.neurobiolaging.2021.12.001). A report comparing original and corrected results can be found onhttps://osf.io/7n3mz/. If you have any questions please contact the corresponding author (sander@mpib-berlin.mpg.de).
DNA methylation affects pre-mRNA transcriptional initiation and processing in Arabidopsis
Authors: Li Qiuhui , Chen Shengjie , Leung Amy Wing-Sze , Liu Yaqin , Xin Yan , Zhang Li , Lam Hon-Ming , Luo Ruibang , Zhang Shoudong
Published: April 2021

Background

DNA methylation may regulate pre-mRNA transcriptional initiation and processing, thus affecting gene expression. Unlike animal cells, plants, especiallyArabidopsis thaliana, have relatively low DNA methylation levels, limiting our ability to observe any correlation between DNA methylation and pre-mRNA processing using typical short-read sequencing. However, with newly developed long-read sequencing technologies, such as Oxford Nanopore Technology Direct RNA sequencing (ONT DRS), combined with whole-genome bisulfite sequencing, we were able to precisely analyze the relationship between DNA methylation and pre-mRNA transcriptional initiation and processing using DNA methylation-related mutants.

Results

Using ONT DRS, we generated more than 2 million high-quality full-length long reads of native mRNA for each of the wild type Col-0 and mutants defective in DNA methylation, identifying a total of 117,474 isoforms. We found that low DNA methylation levels around splicing sites tended to prevent splicing events from occurring. The lengths of the poly(A) tail of mRNAs were positively correlated with DNA methylation. DNA methylation before transcription start sites or around transcription termination sites tended to result in gene-silencing or read-through events.

Furthermore, using ONT DRS, we identified novel transcripts that we could not have otherwise, since transcripts with intron retention and fusion transcripts containing the uncut intergenic sequence tend not to be exported to the cytoplasm. Using themet1-3mutant with activated constitutive heterochromatin regions, we confirmed the effects of DNA methylation on pre-mRNA processing.

Conclusion

The combination of ONT DRS with whole-genome bisulfite sequencing was a powerful tool for studying the effects of DNA methylation on splicing site selection and pre-mRNA processing, and therefore regulation of gene expression.
High-Yield Monocyte, Macrophage, and Dendritic Cell Differentiation from Induced Pluripotent Stem Cells
Authors: Armitage Lucas H. , Khosravi-Maharlooei Mohsen , Meacham Amy , Butfiloski Edward J. , Viola Ryan , Egli Dieter , Sykes Megan , Wallet Mark A. , Mathews Clayton E.
Published: April 2021

Differentiation of induced pluripotent stem cells (iPSC) into monocytes, monocyte-derived macrophages (MDM), and monocyte-derived dendritic cells (moDC) represents a powerful tool for studying human innate immunology and developing novel iPSC-derived immune therapies. Challenges include inefficiencies in iPSC-derived cell cultures, labor-intensive culture conditions, low purity of desired cell types, and feeder cell requirements. Here, a highly efficient method for differentiating monocytes, MDMs, and moDCs that overcomes these challenges is described. The process utilizes commercially-available materials to derive CD34+progenitor cells that are apically released from a hemogenic endothelium. Subsequently, the hemogenic endothelium gives rise to highly pure (>95%), CD34-CD14+monocytes in 19-23 days and yields 13.5-fold more monocytes by day 35 when compared to previous methods. These iPSC-monocytes are analogous to human blood-derived monocytes and readily differentiate into MDM and moDC. The efficient workflow and increase in monocyte output heightens feasibility for high throughput studies and enables clinical-scale iPSC-derived manufacturing processes.
How marine currents and environment shape plankton genomic differentiation: a mosaic view fromTaraOceans metagenomic data
Authors: Laso-Jadart Romuald , O’Malley Michael , Sykulski Adam M. , Ambroise Christophe , Madoui Mohammed-Amin
Published: April 2021

Plankton seascape genomics show different trends from large-scale weak differentiation to micro-scale structures. Prior studies underlined the influence of environment and seascape on a few single species differentiation and adaptation. However, these works generally focused on few single species, sparse molecular markers, or local scales. Here, we investigate the genomic differentiation of plankton at macro-scale in a holistic approach usingTaraOceans metagenomic data together with a reference-free computational method to reconstruct theFST-based genomic differentiation of 113 marine planktonic species using metavariant species (MVS). These MVSs, modelling the species only by their polymorphism, include a wide range of taxonomic groups comprising notably 46 Maxillopoda/Copepoda, 24 Bacteria, 5 Dinoflagellates, 4 Haptophytes, 3 Cnidarians, 3 Mamiellales, 2 Ciliates, 1 Collodaria, 1 Echinoidea, 1 Pelagomonadaceae, 1 Cryptophyta and 1 Virus. The analyses showed that differentiation between populations was significantly lower within basins and higher in bacteria and unicellular eukaryotes compared to zooplantkon. By partitioning the variance of pairwise-FSTmatrices, we found that the main drivers of genomic differentiation were Lagrangian travel time, salinity and temperature. Furthermore, we classified MVSs into parameter-driven groups and showed that taxonomy poorly determines which environmental factor drives genomic differentiation. This holistic approach of plankton genomic differentiation for large geographic scales, a wide range of taxa and different oceanic basins, offers a systematic framework to analyse population genomics of non-model and undocumented marine organisms.
ERK3-MK5 signaling regulates myogenic differentiation and muscle regeneration by promoting FoxO3 degradation
Authors: Soulez Mathilde , Tanguay Pierre-Luc , Dô Florence , Crist Colin , Dort Junio , Kotlyarov Alexey , Gaestel Matthias , Dumont Nicolas A. , Meloche Sylvain
Published: April 2021

The physiological functions and downstream effectors of the atypical mitogen-activated protein kinase ERK3 remain to be characterized. We recently reported that mice expressing catalytically-inactive ERK3 (Mapk6KD/KD) exhibit a reduced post-natal growth rate as compared to control mice. Here, we show that genetic inactivation of ERK3 impairs post-natal skeletal muscle growth and adult muscle regeneration after injury. Loss of MK5 phenocopies the muscle phenotypes ofMapk6KD/KDmice. At the cellular level, genetic or pharmacological inactivation of ERK3 or MK5 induces precocious differentiation of C2C12 or primary myoblasts, concomitant with MyoD activation. Reciprocally, ectopic expression of activated MK5 inhibits myogenic differentiation. Mechanistically, we show that MK5 directly phosphorylates FoxO3, promoting its degradation and reducing its association with MyoD. Depletion of FoxO3 rescues in part the premature differentiation of C2C12 myoblasts observed upon inactivation of ERK3 or MK5. Our findings reveal that ERK3 and its substrate MK5 act in a linear signaling pathway to control post-natal myogenic differentiation.
TheTaxus genome provides insights into paclitaxel biosynthesis
Authors: Xiong Xingyao , Gou Junbo , Liao Qinggang , Li Yanlin , Zhou Qian , Bi Guiqi , Li Chong , Du Ran , Wang Xiaotong , Sun Tianshu , Guo Lvjun , Liang Haifei , Lu Pengjun , Wu Yaoyao , Zhang Zhonghua , Ro Dae-Kyun , Shang Yi , Huang Sanwen , Yan Jianbin
Published: April 2021

The ancient gymnosperm genus Taxus is the exclusive source of the anticancer drug paclitaxel, yet no reference genome sequences are available for comprehensively elucidating the paclitaxel biosynthesis pathway. We have completed a chromosome-level genome ofTaxus chinensisvar.maireiwith a total length of 10.23 Gb. Taxus shared an ancestral whole-genome duplication with the coniferophyte lineage and underwent distinct transposon evolution. We discovered a unique physical and functional grouping ofCYP725As(cytochrome P450) in the Taxus genome for paclitaxel biosynthesis. We also identified a gene cluster in the taxadiene biosynthesis, which was mainly formed by gene duplications. This study will facilitate the elucidation of paclitaxel biosynthesis and unleash the biotechnological potential of Taxus.

One Sentence Summary

A chromosome-level genome assembly ofTaxus chinensisvar.maireiuncovers its unique genome evolution process and genetic architectures for the paclitaxel biosynthesis pathway.
A four-point measurement probe for brain tissue conductivity and permittivity characterization
Authors: Poßner Lucas , Seebeck Lydia , Laukner Matthias , Wilhelmy Florian , Lindner Dirk , Pliquett Uwe , Petkovic Bojana , Ziolkowski Marek , Knösche Thomas R. , Weise Konstantin
Published: April 2021

We present a measurement probe consisting of four platinum electrodes fused into soda-lime glass. The probe is based on a four-terminal sensing technique that uses separate pairs of current-carrying and voltage-sensing electrodes and performs more accurate measurements than the simpler and more usual two-terminal sensing technique. The electrodes are aranged within an area of 1 mm2allowing for local characterization of different brain tissues. The operation of the probe is demonstrated in situ on post mortem porcine brain tissue by measuring the impedance spectra of grey and white matter in a frequency range of 1 kHz <f< 1 MHz. The conductivity and relative permittivity are derived from the impedance spectra using the geometry factor of the probe. The geometry factor is obtained experimentally by measuring the impedances of an electrolytical dilution series with known conductivities. The obtained conductivity of grey matter is in the order of 0.11 S/m and of white matter is in the order of 0.07 S/m over the acquired frequency range.
Librator, a platform for optimized sequence editing, design, and expression of influenza virus proteins
Authors: Li Lei , Stovicek Olivia , Guthmiller Jenna J. , Changrob Siriruk , Fu Yanbin , Dugan Haley L. , Stamper Christopher T. , Zheng Nai-Ying , Huang Min , Wilson Patrick C.
Published: April 2021

Artificial mutagenesis and chimeric/mosaic protein engineering have laid the foundation for antigenic characterization1and universal vaccine design2–4for influenza viruses. However, many methods used for influenza research and vaccine development require sequence editing and protein expression, limiting their applicability and the progress of related research to specialists. Rapid tools allowing even novice influenza researchers to properly analyze and visualize influenza protein sequences with accurate nomenclature are needed to expand the research field. To address this need, we developed Librator, a system for analyzing and designing protein sequences of influenza virus Hemagglutinin (HA) and Neuraminidase (NA). With Librator’s graphical user interface (GUI) and built-in sequence editing functions, biologists can easily analyze influenza sequences and phylogenies, automatically port sequences to visualize structures, then readily mutate target residues and design sequences for antigen probes and chimeric/mosaic proteins efficiently and accurately. This system provides optimized fragment design for Gibson Assembly5of HA and NA expression constructs based on peptide conservation of all historical HA and NA sequences, ensuring fragments are reusable and compatible, allowing for significant reagent savings. Use of Librator will significantly facilitate influenza research and vaccine antigen design.
Patterns of piRNA regulation inDrosophilarevealed through transposable element clade inference
Authors: Said Iskander , McGurk Michael P. , Clark Andrew G. , Barbash Daniel A.
Published: April 2021

Transposable elements (TEs) are self-replicating “genetic parasites” ubiquitous to eukaryotic genomes. In addition to conflict between TEs and their host genomes, TEs of the same family are in competition with each other. They compete for the same genomic niches while experiencing the same regime of copy-number selection. This suggests that competition among TEs may favor the emergence of new variants that can outcompete their ancestral forms. To investigate the sequence evolution of TEs, we developed a method to infer clades: collections of TEs that share SNP variants and represent distinct TE family lineages. We applied this method to a panel of 85Drosophila melanogastergenomes and found that the genetic variation of several TE families shows significant population structure that arises from the population- specific expansions of single clades. We used population genetic theory to classify these clades into younger versus older clades and found that younger clades are associated with a greater abundance of sense and antisense piRNAs per copy than older ones. Further, we find that the abundance of younger, but not older clades, is positively correlated with antisense piRNA production, suggesting a general pattern where hosts preferentially produce antisense piRNAs from recently active TE variants. Together these findings suggest a pattern whereby new TE variants arise by mutation and then increase in copy number, followed by the host producing antisense piRNAs that may be used to silence these emerging variants.
Simple degradable cyclodextrin polyester with chelator-based crosslinker for stent-based drug delivery
Authors: Young Kathleen , Lord Audrey E. , Burkhart Grace E. , Kozawa Susan K. , Mu Nathan , von Recum Horst A.
Published: April 2021

Cyclodextrins are a class of molecules which inclusion complexes with small hydrophobic drugs, and has historically been used to improve solubility and bioavailability of labile drugs in pharmaceutical applications. More recently, polymerized cyclodextrin has been applied in various applications as implantable drug delivery depots and as medical device coatings (e.g. polymeric hernia meshes) due to their ability to sustain and control drug delivery as well as prevent biofouling. Cyclodextrin polymers as coatings for metal medical devices, like screws or stents, is less explored; due to the high mechanical property mismatch between polymers and metals, a polymer coating is liable to delaminate easily, especially during device deformation. Novel methods for facilitating attachment to metal substrates have been explored, but coating longevity is still an issue, and these methods typically require the use of multiple reagents and complex methods. We report here the development and characterization of a cyclodextrin polymer with a chelator-based crosslinker with respect to appearance, chemistry, drug release profiles, erosion, pH-dependence. We found that increasing the crosslinking ratio (crosslinker:cyclodextrin) slowed down degradation and decreased drug loading as well. Drug release of the anti-restenotic drug sirolimus proceeded for over 4 weeks. The ability of the polymer to stably coat metal stents was verified, and the coating procedure is a simple, single step protocol.