bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single cell analysis of spondyloarthritis regulatory T cells identifies distinct synovial gene expression patterns and clonal fates
Authors: Simone Davide , Penkava Frank , Ridley Anna , Sansom Stephen , Al-Mossawi M Hussein , Bowness Paul 
Published: May 2021

AbstractRegulatory T cells (Tregs) play an important role in controlling inflammation and limiting autoimmunity, but their phenotypes at inflammatory sites in human disease are poorly understood. We here analyze the single-cell transcriptome of >16,000 Tregs obtained from peripheral blood and synovial fluid of two patients with HLA-B27+ ankylosing spondylitis and three patients with psoriatic arthritis, closely related forms of inflammatory spondyloarthritis. We identify multiple Treg clusters with distinct transcriptomic profiles, including, among others, a regulatory CD8+subset expressing cytotoxic markers/genes, and a Th17-likeRORC+ Treg subset characterized by IL-10 and LAG-3 expression. Synovial Tregs show upregulation of interferon signature and TNF receptor superfamily genes, and marked clonal expansion, consistent with tissue adaptation and antigen contact respectively. Individual synovial Treg clones map to different clusters indicating cell fate divergence. Finally, we demonstrate that LAG-3 directly inhibits IL-12/23 and TNF secretion by patient-derived monocytes, a mechanism with translational potential in SpA. Our detailed characterization of Tregs at an important inflammatory site illustrates the marked specialization of Treg subpopulations.
Structural and functional connectivity reconstruction with CATO - A Connectivity Analysis TOolbox
Authors: de Lange Siemon C. , Helwegen Koen , van den Heuvel Martijn P. 
Published: May 2021

AbstractWe describe a Connectivity Analysis TOolbox (CATO) for the reconstruction of structural and functional brain connectivity based on diffusion weighted imaging and resting-state functional MRI data. CATO is a multimodal software package that enables researchers to run end-to-end reconstructions from MRI data to structural and functional connectome maps, customize their analyses and utilize various software packages to preprocess data. Structural and functional connectome maps can be reconstructed with respect to user-defined (sub)cortical atlases providing aligned connectivity matrices for integrative multimodal analyses. We outline the implementation and usage of the structural and functional processing pipelines in CATO. Performance was calibrated with respect to simulated diffusion weighted imaging from the ITC2015 challenge, test-retest diffusion weighted imaging data and resting-state functional MRI data from the Human Connectome Project. CATO is open-source software distributed under the MIT License and available as a MATLAB toolbox and as a stand-alone application atwww.dutchconnectomelab.nl/CATO.
Distinct gene regulatory signatures of dominance rank and social bond strength in wild baboons
Authors: Anderson Jordan A. , Lea Amanda J. , Voyles Tawni N. , Akinyi Mercy Y. , Nyakundi Ruth , Ochola Lucy , Omondi Martin , Nyundo Fred , Zhang Yingying , Campos Fernando A. , Alberts Susan C. , Archie Elizabeth A. , Tung Jenny 
Published: May 2021

AbstractThe social environment is a major determinant of morbidity, mortality, and Darwinian fitness in social animals. Recent studies have begun to uncover the molecular processes associated with these relationships, but the degree to which they vary across different dimensions of the social environment remains unclear. Here, we draw on a long-term field study of wild baboons to compare the signatures of affiliative and competitive aspects of the social environment in white blood cell gene regulation, under both immune stimulated and non-stimulated conditions. We find that the effects of dominance rank on gene expression are directionally opposite in males versus females, such that high-ranking males resemble low-ranking females, and vice-versa. Among females, rank and social bond strength are both reflected in the activity of cellular metabolism and proliferation genes. However, pronounced rank-related differences in baseline immune gene activity are near-absent for social bond strength, while only bond strength predicts the fold-change response to immune (lipopolysaccharide) stimulation. Together, our results indicate that the directionality and magnitude of social effects on gene regulation depend on the aspect of the social environment under study. This heterogeneity may help explain why social environmental effects on health and longevity can also vary between measures.
Co-expression patterns of microglia markers Iba1, TMEM119 and P2RY12 in Alzheimer’s disease
Authors: Kenkhuis Boyd , Somarakis Antonios , Kleindouwel Lynn RT , van Roon-Mom Willeke MC , Höllt Thomas , van der Weerd Louise 
Published: May 2021

AbstractMicroglia have been identified as key players in Alzheimer’s disease pathogenesis, and other neurodegenerative diseases. Iba1, and more specifically TMEM119 and P2RY12 are gaining ground as presumedly more specific microglia markers, but comprehensive characterization of the expression of these three markers individually as well as combined is currently missing. Here we used a multispectral immunofluorescence dataset, in which over seventy thousand microglia from both aged controls and Alzheimer patients have been analysed for expression of Iba1, TMEM119 and P2RY12 on a single-cell level. For all markers, we studied the overlap and differences in expression patterns and the effect of proximity to β-amyloid plaques. We found no difference in absolute microglia numbers between control and Alzheimer subjects, but the prevalence of specific combinations of markers (phenotypes) differed greatly. In controls, the majority of microglia expressed all three markers. In Alzheimer patients, a significant loss of TMEM119+-phenotypes was observed, independent of the presence of β-amyloid plaques in its proximity. Contrary, phenotypes showing loss of P2RY12, but consistent Iba1 expression were increasingly prevalent around β-amyloid plaques. No morphological features were conclusively associated with loss or gain of any of the markers or any of the identified phenotypes. All in all, none of the three markers were expressed by all microglia, nor can be wholly regarded as a pan- or homeostatic marker, and preferential phenotypes were observed depending on the surrounding pathological or homeostatic environment. This work could help select and interpret microglia markers in previous and future studies.
An ancient divide in outer membrane tethering systems in Bacteria
Authors: Witwinowski Jerzy , Sartori-Rupp Anna , Taib Najwa , Pende Nika , Tham To Nam , Poppleton Daniel , Ghigo Jean-Marc , Beloin Christophe , Gribaldo Simonetta 
Published: May 2021

AbstractRecent data support the hypothesis that Gram-positive bacteria (monoderms) arose from Gram-negatives (diderms) through loss of the outer membrane (OM). However how this happened remains unknown. Considering that tethering of the OM is essential for cell envelope stability in diderm bacteria we hypothesize that its destabilization may have been involved in OM loss. Here, we present an in-depth analysis of the four main OM tethering systems across all Bacteria. We show that their distribution strikingly follows the bacterial phylogeny with a bimodal distribution matching the deepest phylogenetic cleavage between Terrabacteria (a clade encompassing Cyanobacteria, Deinococcus/Thermus, Firmicutes, etc.) and Gracilicutes (a clade encompassing Proteobacteria, Bacteroidetes, Spirochaetes, etc.). Diderm Terrabacteria display as the main system OmpM, a porin that attaches non-covalently to modified peptidoglycan or to secondary cell wall polymers. In contrast, the lipoprotein Pal is restricted to the Gracilicutes along with a more sporadic occurrence of OmpA. While Braun’s lipoprotein Lpp is largely considered as the textbook example of OM attachment, it is actually present only in a subclade of Gammaproteobacteria. We propose an evolutionary scenario whereby the last common bacterial ancestor used a system based on OmpM, which was later replaced by one based on the lipoprotein Pal concomitantly to the emergence of the Lol machinery to address lipoproteins to the OM, with OmpA as a possible transition state. We speculate that the existence of only one main OM tethering system in the Terrabacteria would have allowed the multiple emergences of the monoderm phenotype specifically observed in this clade through OmpM perturbation. We test this hypothesis by inactivating all four ompM gene copies in the genetically tractable diderm Firmicute Veillonella parvula. The resulting mutant is severely affected in growth and displays high sensitivity to OM stress. High resolution imaging and tomogram reconstructions reveal a dramatic - yet non-lethal - phenotype, in which vast portions of the OM detach, producing large vesicles surrounding multiple monoderm-like cells sharing a common periplasm. Complementation by a single OmpM rescues the phenotype to a normal cell envelope. Together, our results highlight an ancient shift in bacterial evolution involving OM tethering systems. They suggest a possible mechanism for OM loss and a high flexibility of the cell envelope in diderm Firmicutes, making them ideal models to further refine our understanding of the mechanisms involved in bacterial OM stability, and opening the way to recapitulate the monoderm/diderm transition in the laboratory.
A modular mathematical model of exercise-induced changes in metabolism, signaling, and gene expression in human skeletal muscle
Authors: Akberdin I.R. , Kiselev I.N. , Pintus S.S. , Sharipov R.N. , Vertyshev A.Yu. , Vinogradova O.L. , Popov D.V. , Kolpakov F.A. 
Published: May 2021

AbstractSkeletal muscle is the principal contributor to exercise-induced changes in human metabolism. Strikingly, although it has been demonstrated that a lot of metabolites accumulating in blood and human skeletal muscle during an exercise activate different signaling pathways and induce expression of many genes in working muscle fibres, the system understanding of signaling-metabolic pathways interrelations with downstream genetic regulation in the skeletal muscle is still elusive. Herein, a physiologically based computational model of skeletal muscle comprising energy metabolism, Ca2+and AMPK signalling pathways, and expression regulation of genes with early and delayed responses has been developed based on a modular modeling approach. The integrated modular model validated on diverse including original experimental data and different exercise modes provides a comprehensivein silicoplatform in order to decipher and track cause-effect relationships between metabolic, signaling and gene expression levels in the skeletal muscle.
The molecular basis of ubiquitin-specific protease 8 autoinhibition by the WW-like domain
Authors: Kakihara Keijun , Asamizu Kengo , Moritsugu Kei , Kubo Masahide , Kitaguchi Tetsuya , Endo Akinori , Kidera Akinori , Ikeguchi Mitsunori , Kato Akira , Komada Masayuki , Fukushima Toshiaki 
Published: May 2021

AbstractUbiquitin-specific protease 8 (USP8) is a deubiquitinating enzyme involved in multiple membrane trafficking pathways. The enzyme activity is inhibited by binding to 14-3-3 proteins, and mutations of the 14-3-3 binding motif in USP8 are related to Cushing’s disease. However, the molecular basis of USP8 enzyme activity regulation remains unclear. Here, we identified amino acids 645–684 of USP8 as an autoinhibitory region, which our pull-down and single-molecule FRET assay results suggested interacts with the catalytic USP domain.In silicomodelling indicated that the region forms a WW-like domain structure, plugs the catalytic cleft, and narrows the entrance to the ubiquitin-binding pocket. Furthermore, 14-3-3 was found to inhibit USP8 enzyme activity partly by enhancing the interaction between the WW-like and USP domains. These findings provide the molecular basis of USP8 autoinhibition via the WW-like domain. Moreover, they suggest that the release of autoinhibition may underlie Cushing’s disease caused by USP8 mutations.
Evolution of brilliant iridescent feather nanostructures
Authors: Nordén Klara K. , Eliason Chad M. , Stoddard Mary Caswell 
Published: May 2021

AbstractThe brilliant iridescent plumage of birds creates some of the most stunning color displays known in the natural world. Iridescent plumage colors are produced by nanostructures in feathers and have evolved in a wide variety of birds. The building blocks of these structures—melanosomes (melanin-filled organelles)—come in a variety of forms, yet how these different forms contribute to color production across birds remains unclear. Here, we leverage evolutionary analyses, optical simulations and reflectance spectrophotometry to uncover general principles that govern the production of brilliant iridescence. We find that a key feature that unites all melanosome forms in brilliant iridescent structures is thin melanin layers. Birds have achieved this in multiple ways: by decreasing the size of the melanosome directly, by hollowing out the interior, or by flattening the melanosome into a platelet. The evolution of thin melanin layers unlocks color-producing possibilities, more than doubling the range of colors that can be produced with a thick melanin layer and simultaneously increasing brightness. We discuss the implications of these findings for the evolution of iridescent structures in birds and propose two evolutionary paths to brilliant iridescence.
Transcriptional characterization of the glial response due to chronic neural implantation of flexible microprobes
Authors: Joseph Kevin , Kirsch Matthias , Johnston Midori , Münkel Christian , Stieglitz Thomas , Haas Carola A. , Hofmann Ulrich G. 
Published: May 2021

AbstractLong term implantation of (micro-)probes into neural tissue cause unique and disruptive responses to these foreign bodies. In this study, we present the transcriptional trajectory of glial cells responding to chronic implantation of flexible micro-probes for up to 18 weeks. Transcriptome analysis shows a rapid activation of microglial cells and a strong upregulation of reactive astrocytic genes, which is lost over the full duration of the implant period. Most interestingly, animals that were implanted for 18 weeks show a transcriptional profile similar to non-implanted controls, with increased expression of genes associated with wound healing and angiogenesis, which raises hope of a normalization of the neuropil to the pre-injury state when using flexible probes. Nevertheless, our data show, that a subset of genes upregulated after 18 weeks belong to the family of immediate early genes, which would indicate that structural and functional remodeling has not been completed at this time point. Our results confirm and extend previous work on the molecular changes resulting from the presence of intraneural probes and provide a rational basis for developing intervention strategies to control them.
Tetracycline exposure alters key gut microbiota in Africanized honey bees (Apis mellifera scutellatax spp.)
Authors: Soares Kilmer Oliveira , de Oliveira Celso José Bruno , Rodrigues Adriana Evangelista , Vasconcelos Priscylla Carvalho , da Silva Núbia Michelle Vieira , da Cunha Filho Octavio Gomes , Madden Christopher , Hale Vanessa L. 
Published: May 2021

AbstractHoney bees play a critical role in ecosystem health, biodiversity maintenance, and crop yield. Antimicrobials, such as tetracyclines, are used widely used across agriculture, medicine, and in bee keeping, and bees can be directly or indirectly exposed to tetracycline residues in the environment. In European honey bees, tetracycline exposure has been linked with shifts in the gut microbiota that negatively impact bee health. However, the effects of antimicrobials on Africanized honey bee gut microbiota have not been examined. The aim of this study was to investigate the effects of tetracycline exposure on the gut microbial community of Africanized honey bees (Apis mellifera scutellatax spp), which are important pollinators in South, Central, and North America. Bees (n=1,000) were collected from hives in Areia-PB, Northeastern Brazil, placed into plastic chambers and kept under controlled temperature and humidity conditions. The control group (CON) was fed daily with syrup (10g) consisting of a 1:1 solution of demerara sugar and water, plus a solid protein diet (10g) composed of 60% soy extract and 40% sugar syrup. The tetracycline group (TET) was fed identically but with the addition of tetracycline hydrochloride (450 µg/g) to the sugar syrup. Bees were sampled from each group before (day 0), and after tetracycline exposure (days 3, 6 and 9). Abdominal contents dissected out of each bee underwent DNA extraction and 16S rRNA sequencing (V3-V4) on an Illumina MiSeq. Sequences were filtered and processed through QIIME2 and DADA2. Microbial community composition and diversity and differentially abundant taxa were evaluated by treatment and time. Bee gut microbial composition (Jaccard) and diversity (Shannon) differed significantly and increasingly over time and between CON and TET groups. Tetracycline exposure was associated with decreased relative abundances ofBombellaandFructobacillus, along with decreases in key core microbiota such asSnodgrassella, Gilliamella, Rhizobiaceae, andApibacter. These microbes are critical for nutrient metabolism and pathogen defense, and decreased abundances of these microbes could negatively affect bee health. Considering the global ecological and economic importance of honey bees as pollinators, it is critical to understand the effects of agrochemicals including antimicrobials on honey bees.
Successful intergeneric transfer of a major apple scab resistance gene (Rvi6) from apple to pear and precise comparison of the downstream molecular mechanisms of this resistance in both species
Authors: Perchepied L. , Chevreau E. , Ravon E. , Gaillard S. , Pelletier S. , Bahut M. , Berthelot P. , Cournol R. , Schouten H.J. , Vergne E. 
Published: May 2021

AbstractBackgroundScab is the most important fungal disease of apple and pear. Apple (Malus x domesticaBorkh.) and European pear (Pyrus communisL.) are genetically related but they are hosts of two different fungal species:Venturia inaequalisfor apple andV. pyrinafor European pear. The apple/V. inaequalispathosystem is quite well known, whereas knowledge about the pear/V. pyrinapathosystem is still limited. The aim of our study was to analyse the mode of action of a major resistance gene of apple (Rvi6) in transgenic apple and pear plants interacting with the two scab species (V. inaequalisandV. pyrina), in order to determine the degree of functional transferability between the two pathosystems.ResultsTransgenic pear clones constitutively expressing theRvi6gene from apple were compared to a scab transgenic apple clone carrying the same construct. After inoculation in greenhouse withV. pyrina, strong defense reactions and very limited sporulation were observed on all transgenic pear clones tested. Microscopic observations revealed frequent aborted conidiophores in theRvi6transgenic pear /V. pyrinainteraction. The macro- and microscopic observations were very comparable to theRvi6apple /V. inaequalisinteraction. However, this resistance in pear proved variable according to the strain ofV. pyrina, and one of the strains tested overcame the resistance of most of the transgenic pear clones. Comparative transcriptomic analyses of apple and pear resistant interactions withV. inaequalisandV. pyrina, respectively, revealed different cascades of molecular mechanisms downstream of the pathogen recognition byRvi6in the two species. Signal transduction was triggered in both species with calcium (and G-proteins in pear) and interconnected hormonal signaling (jasmonic acid in pear, auxins in apple and brassinosteroids in both species), without involvement of salicylic acid. This led to the induction of defense responses such as a remodeling of primary and secondary cell wall, lipids biosynthesis (galactolipids in apple and cutin and cuticular waxes in pear), systemic acquired resistance signal generation (in apple) or perception in distal tissues (in pear), and the biosynthesis of phenylpropanoids (flavonoids in apple but also lignin in pear).ConclusionThis study is the first example of a successful intergeneric transfer of a resistance gene amongRosaceae, with a resistance gene functioning towards another species of pathogen.
The role of occupational meaningfulness and citizenship as mediators between occupational status and recovery: a cross-sectional study among residents with co-occurring problems
Authors: Nesse Linda , Aamodt Geir , Gonzalez Marianne Thorsen , Rowe Michael , Raanaas Ruth Kjærsti 
Published: May 2021

Purpose
Engagement in meaningful occupations and being included as full citizens of the community, is essential in everyday life, and may be of considerable relevance for recovery and quality of life. However, persons with co-occurring substance use and mental health problems experience extensive obstacles to engagement in occupations and citizenship. The relationship between objective measures of occupational status and subjective experiences of occupational meaningfulness, citizenship and recovery, is scarcely researched in the context of co-occurring problems. As such, the purpose of this study is to examine associations between occupational status, occupational meaningfulness, citizenship and recovery and quality of life and to examine the roles of occupational meaningfulness and citizenship as possible mediators between occupational status and recovery and quality of life.

Design/methodology/approach
The study used a cross-sectional design with a sample of 104 residents at supported housing sites across six Norwegian cities.

Findings
Linear regression analyzes indicated that occupational status was significantly associated with the citizenship domains caring for others and community participation and with the quality of life measure positive affect. Occupational meaningfulness and citizenship were significantly associated with different domains of recovery and quality of life. Furthermore, mediation analyzes showed that the relationship between occupational status and recovery and quality of life was mediated by caring for others and community participation.

Originality/value
The results suggest that emphasizing opportunities for occupational meaningfulness and citizenship in practice may have positive implications for recovery among persons with co-occurring problems.
Innovation in banking: fusion of artificial intelligence and blockchain
Authors: R. Vedapradha , Ravi Hariharan 
Published: May 2021

Purpose
This study aims to analyze the importance of disruptive technological innovations on qualitative service delivery and their impact on the investment banks’ employee performance.

Design/methodology/approach
The cluster sampling method has been used to collect the primary data from the 250 respondents from foreign investment banks. Variables used are employee performance, service delivery, technology, security, operations, strategy and quality through chi-square, linear stepwise multiple regression analysis and correlation.

Findings
Storage network, operating cost, client reporting, cloud system and money laundering are the highest and most significant predictors of employee performance. Employee performance multiplies every unit with a strategic solution owing to positive and robust correlation (0.944). Fusion technology-based banks offer quality service to their clients.

Originality/value
A combination of artificial intelligence and blockchain ensures increasing automation to improve efficiency and reduce the operating cost creating a seamless integration in fraud detection, customer support, risk management, security, digitization and automation process, algorithmic trading, wealth management, etc.