scholarly journals OP0099 FUNCTIONAL MAPPING OF SYNOVIAL FIBROBLAST POPULATIONS IN HEALTH AND ARTHRITIC DISEASE: INSIGHTS INTO THE PATHOGENIC REMODELING OF SYNOVIAL MICROENVIRONMENT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 65.1-65
Author(s):  
D. Konstantopoulos ◽  
C. Tzaferis ◽  
M. Sakkou ◽  
A. Liakos ◽  
M. Lavigne ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Meta Analysis ◽  
Synovial Fibroblasts ◽  
Chronic Arthritis ◽  
Arthritic Disease ◽  
Serum Transfer ◽  
Reported Data ◽  
Inflammatory Phenotypes ◽  
Epigenetic Signatures

Background:Our previous studies highlighted the fundamental in vivo role of synovial fibroblasts (SFs) in TNF-mediated murine chronic arthritis1,2and recent findings identified different SF identities based on their transcriptomic profiles with distinct contributions in acute, autoimmunity-based, murine arthritis3.Objectives:In this study, we focus on delineating the map of SF subpopulations in healthy joint and in the course of arthritic disease and the underlying regulatory networks functioning towards pathogenicity.Methods:Sorted single cell suspensions (CD45-, Pdpl+) and their fragmented nuclei from synovial joints of WT, early and late arthritic hTNFtg mice were processed for scRNAseq and scATAC employing a droplet-based technology (10x Genomics). To define the transcriptional and epigenetic signatures originating from the two different assays, we developed an integrative analysis pipeline based on the Seurat software package (v3.1). Meta-analysis of previously reported data of K/BxN serum transfer of arthritis was employed to define commonalities and differences in SF subsets among murine modelled disease.Results:The transition from healthy to chronically affected synovial microenvironment (SME) due to overexpression of hTNF is characterized by a dynamic transformation of SF clusters. The Lining arthritic Thy1lowsynovial layer (L-SFs) is hyper-populated while Sub-Lining Thy1highSF clusters (SL-SFs) are remodeled towards catabolic and inflammatory phenotypes compared to naïve SF organization pattern. Interestingly, trajectory analysis revealed that the SL clusters, which normally exhibit a gradual developmental-like process towards different profiles, differentially change during disease. We identified that the previously reported proliferating SL cluster is absent in healthy synovium, dominates mainly in early stages of chronic arthritis and it is closely related to the L-SFs. Mapping of the gene regulatory networks by RNAseq was supported by scATAC analysis. Similarly, meta-analysis of SF profiles derived from naïve and the K/BxN-serum–treated mice showed significant differences, possibly reflecting the phenotypes of the two established models of arthritis.Conclusion:Our approach unravels for the first time the regulatory heterogeneity and gene expression profiling of SF subpopulations in normal synovium, and reveals deep biological insights of the functional re-organization of SME during development of disease. It further identifies the common and divergent features of the different subtypes of murine arthritis that may well reflect the diversity of RA subtypes and the response to therapies.References:[1]Armaka et al; J Exp Med (2008): 205(2):331-7.[2]Armaka et al; Nat Commun (2018): 9(1):618.[3]Croft et al; Nature (2019): 570(7760):246-251.Disclosure of Interests:None declared

scholarly journals P89 Patient reported comorbidity is not a reliable data source: a systematic review of the literature

BJS Open ◽  
2021 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
Chung Mun Alice Lin ◽  
Alexander Orman ◽  
Nicholas D Clement ◽  
David J Deehan ◽  
Chung M A Lin
Keyword(s):  
Medical Record ◽  
Meta Analysis ◽  
Analysis Data ◽  
Fundamental Factor ◽  
Resource Limitations ◽  
Patient Reported ◽  
Data Source ◽  
Reported Data ◽  
Operative Assessment ◽  
Source Of Information

Abstract Introduction There is currently an increased demand for elective orthopaedic surgery. However, due to the ever-growing financial, time and resource limitations, there is a pressing need to identify those who would benefit most from surgery but with the lowest risk of complications. Comorbidities are a fundamental factor in this decision and the traditional way to ascertain this is through medical record data abstraction during pre-operative assessment. However, this can be time consuming and expensive. We therefore set out to establish whether patient reported comorbidities are reliable as a principal source of information. Method Searches were performed on PubMed and Medline, and citations independently screened. Included studies were published between 2010 to 2020 assessing the reliability of at least one patient reported comorbidity against their medical record or clinical assessment as gold standard. Cohen’s kappa coefficient values were grouped into systems and a meta-analysis performed comparing the reliability between studies. Results Meta-analysis data showed poor-to-moderate reliability for diseases in cardiovascular, musculoskeletal, neurological and respiratory systems as well as for malignancy and depression. Endocrine diseases showed good-to-excellent reliability. Factors found to affect the concordance included sex, age, ethnicity, education, living alone, marital status, number or severity of comorbidities, mental health and disability. Conclusion Our study showed poor-to-moderate reliability for all systems except endocrine, consisting of thyroid disease and diabetes mellitus, which demonstrated good-to-excellent reliability. Although patient reported data is useful and can facilitate a complete pre-operative overview of the patient, it is not reliable enough to be used as a standalone measure.

scholarly journals Disentangling transcriptional responses in plant defense against arthropod herbivores

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alejandro Garcia ◽  
M. Estrella Santamaria ◽  
Isabel Diaz ◽  
Manuel Martinez
Keyword(s):  
Regulatory Networks ◽  
Pieris Rapae ◽  
Meta Analysis ◽  
Plant Response ◽  
Plant Responses ◽  
Transcriptional Responses ◽  
Crop Species ◽  
Physiological Processes ◽  
Meta Analyses ◽  
Plant Herbivore

AbstractThe success in the response of a plant to a pest depends on the regulatory networks that connect plant perception and plant response. Meta-analyses of transcriptomic responses are valuable tools to discover novel mechanisms in the plant/herbivore interplay. Considering the quantity and quality of available transcriptomic analyses, Arabidopsis thaliana was selected to test the ability of comprehensive meta-analyses to disentangle plant responses. The analysis of the transcriptomic data showed a general induction of biological processes commonly associated with the response to herbivory, like jasmonate signaling or glucosinolate biosynthesis. However, an uneven induction of many genes belonging to these biological categories was found, which was likely associated with the particularities of each specific Arabidopsis-herbivore interaction. A thorough analysis of the responses to the lepidopteran Pieris rapae and the spider mite Tetranychus urticae highlighted specificities in the perception and signaling pathways associated with the expression of receptors and transcription factors. This information was translated to a variable alteration of secondary metabolic pathways. In conclusion, transcriptomic meta-analysis has been revealed as a potent way to sort out relevant physiological processes in the plant response to herbivores. Translation of these transcriptomic-based analyses to crop species will permit a more appropriate design of biotechnological programs.

scholarly journals Novel Identified Circular Transcript of RCAN2, circ-RCAN2, Shows Deviated Expression Pattern in Pig Reperfused Infarcted Myocardium and Hypoxic Porcine Cardiac Progenitor Cells In Vitro

2021 ◽  
Vol 22 (3) ◽  
pp. 1390
Author(s):  
Julia Mester-Tonczar ◽  
Patrick Einzinger ◽  
Johannes Winkler ◽  
Nina Kastner ◽  
Andreas Spannbauer ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Progenitor Cells ◽  
Regulatory Networks ◽  
Circular Rnas ◽  
Cardiac Progenitor Cells ◽  
Tissue Samples ◽  
Healthy Myocardium ◽  
Acute Mi

Circular RNAs (circRNAs) are crucial in gene regulatory networks and disease development, yet circRNA expression in myocardial infarction (MI) is poorly understood. Here, we harvested myocardium samples from domestic pigs 3 days after closed-chest reperfused MI or sham surgery. Cardiac circRNAs were identified by RNA-sequencing of rRNA-depleted RNA from infarcted and healthy myocardium tissue samples. Bioinformatics analysis was performed using the CIRIfull and KNIFE algorithms, and circRNAs identified with both algorithms were subjected to differential expression (DE) analysis and validation by qPCR. Circ-RCAN2 and circ-C12orf29 expressions were significantly downregulated in infarcted tissue compared to healthy pig heart. Sanger sequencing was performed to identify the backsplice junctions of circular transcripts. Finally, we compared the expressions of circ-C12orf29 and circ-RCAN2 between porcine cardiac progenitor cells (pCPCs) that were incubated in a hypoxia chamber for different time periods versus normoxic pCPCs. Circ-C12orf29 did not show significant DE in vitro, whereas circ-RCAN2 exhibited significant ischemia-time-dependent upregulation in hypoxic pCPCs. Overall, our results revealed novel cardiac circRNAs with DE patterns in pCPCs, and in infarcted and healthy myocardium. Circ-RCAN2 exhibited differential regulation by myocardial infarction in vivo and by hypoxia in vitro. These results will improve our understanding of circRNA regulation during acute MI.

scholarly journals RNA-Centric Approaches to Profile the RNA–Protein Interaction Landscape on Selected RNAs

2021 ◽  
Vol 7 (1) ◽  
pp. 11 ◽  
Author(s):  
André P. Gerber
Keyword(s):  
Mass Spectrometry ◽  
Protein Interactions ◽  
Regulatory Networks ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Protein Complexes ◽  
Cell Protein ◽  
Transcriptional Regulatory Networks ◽  
Technological Advances

RNA–protein interactions frame post-transcriptional regulatory networks and modulate transcription and epigenetics. While the technological advances in RNA sequencing have significantly expanded the repertoire of RNAs, recently developed biochemical approaches combined with sensitive mass-spectrometry have revealed hundreds of previously unrecognized and potentially novel RNA-binding proteins. Nevertheless, a major challenge remains to understand how the thousands of RNA molecules and their interacting proteins assemble and control the fate of each individual RNA in a cell. Here, I review recent methodological advances to approach this problem through systematic identification of proteins that interact with particular RNAs in living cells. Thereby, a specific focus is given to in vivo approaches that involve crosslinking of RNA–protein interactions through ultraviolet irradiation or treatment of cells with chemicals, followed by capture of the RNA under study with antisense-oligonucleotides and identification of bound proteins with mass-spectrometry. Several recent studies defining interactomes of long non-coding RNAs, viral RNAs, as well as mRNAs are highlighted, and short reference is given to recent in-cell protein labeling techniques. These recent experimental improvements could open the door for broader applications and to study the remodeling of RNA–protein complexes upon different environmental cues and in disease.

scholarly journals Effectiveness and mechanisms of adipose-derived stem cell therapy in animal models of Parkinson’s disease: a systematic review and meta-analysis

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Keya Li ◽  
Xinyue Li ◽  
Guiying Shi ◽  
Xuepei Lei ◽  
Yiying Huang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Therapeutic Option ◽  
Meta Analysis ◽  
Future Application ◽  
Neuroprotective Effects ◽  
Standard Mean Difference ◽  
Study Characteristics

AbstractAnimal models provide an opportunity to assess the optimal treatment way and the underlying mechanisms of direct clinical application of adipose-derived stem cells (ADSCs). Previous studies have evaluated the effects of primitive and induced ADSCs in animal models of Parkinson’s disease (PD). Here, eight databases were systematically searched for studies on the effects and in vivo changes caused by ADSC intervention. Quality assessment was conducted using a 10-item risk of bias tool. For the subsequent meta-analysis, study characteristics were extracted and effect sizes were computed. Ten out of 2324 published articles (n = 169 animals) were selected for further meta-analysis. After ADSC therapy, the rotation behavior (10 experiments, n = 156 animals) and rotarod performance (3 experiments, n = 54 animals) were improved (P < 0.000 01 and P = 0.000 3, respectively). The rotation behavior test reflected functional recovery, which may be due to the neurogenesis from neuronally differentiated ADSCs, resulting in a higher pooled effect size of standard mean difference (SMD) (− 2.59; 95% CI, − 3.57 to − 1.61) when compared to that of primitive cells (− 2.18; 95% CI, − 3.29 to − 1.07). Stratified analyses by different time intervals indicated that ADSC intervention exhibited a long-term effect. Following the transplantation of ADSCs, tyrosine hydroxylase-positive neurons recovered in the lesion area with pooled SMD of 13.36 [6.85, 19.86]. Transplantation of ADSCs is a therapeutic option that shows long-lasting effects in animal models of PD. The potential mechanisms of ADSCs involve neurogenesis and neuroprotective effects. The standardized induction of neural form of transplanted ADSCs can lead to a future application in clinical practice.

Left Out But “In Control”? Culture Variations in Perceived Control When Excluded by a Close Other

2021 ◽  
pp. 194855062098743
Author(s):  
Sasha Y. Kimel ◽  
Dominik Mischkowski ◽  
Yuki Miyagawa ◽  
Yu Niiya
Keyword(s):  
Asian Americans ◽  
Perceived Control ◽  
Meta Analysis ◽  
Well Being ◽  
Control Culture ◽  
Good Friend ◽  
Cultural Groups ◽  
Cultural Variations ◽  
European Americans

Research and theorizing suggest two competing—yet untested—hypotheses for how European Americans’ and Asians’ feeling of being “in control” might differ when excluded by a close other (e.g., a good friend). Drawing on different national contexts (i.e., United States, Japan), cultural groups (i.e., Japanese, Asian/Asian Americans, European Americans), and exclusion paradigms (i.e., relived, in vivo), four separate experiments ( N = 2,662) examined feelings of control when excluded by a close- or distant-other. A meta-analysis across these experiments indicated that Asians and Asian Americans felt more in control than European Americans when the excluder was a close other. In contrast, no consistent pattern emerged when the excluder was a distant other. This research has implications for cultural variations in aggressiveness as well as health and well-being following exclusion’s threat to perceived control.

In vivo praziquantel efficacy of Schistosoma japonicum over time: a systematic review and meta-analysis

Acta Tropica ◽  
2021 ◽  
pp. 106048
Author(s):  
Qiu-Fu Yu ◽  
Jie-Ying Zhang ◽  
Meng-Tao Sun ◽  
Man-Man Gu ◽  
Hui-Ying Zou ◽  
...  
Keyword(s):  
Systematic Review ◽  
Schistosoma Japonicum ◽  
Meta Analysis ◽  
Over Time

scholarly journals Assessment of Conjugate Complexes of Chitosan and Urtica dioica or Equisetum arvense Extracts for the Control of Grapevine Trunk Pathogens

Agronomy ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 976
Author(s):  
Natalia Langa-Lomba ◽  
Laura Buzón-Durán ◽  
Pablo Martín-Ramos ◽  
José Casanova-Gascón ◽  
Jesús Martín-Gil ◽  
...  
Keyword(s):  
Urtica Dioica ◽  
Gas Chromatography Mass Spectrometry ◽  
Equisetum Arvense ◽  
Grapevine Trunk Diseases ◽  
Trunk Diseases ◽  
Synergistic Behavior ◽  
Reported Data ◽  
Basic Substances

In the work presented herein, we analyze the efficacy of three basic substances that comply with European Regulation (EC) No 1107/2009, namely chitosan, horsetail (Equisetum arvense L.) and nettle (Urtica dioica L.), for the control of grapevine trunk diseases (GTDs) in organic farming. The E. arvense and U. dioica aqueous extracts, prepared according to SANCO/12386/2013 and SANTE/11809/2016, have been studied by gas chromatography–mass spectrometry (GC-MS), identifying their main active constituents. The three basic substances, either alone or in combination (forming conjugate complexes), have been tested in vitro against eight Botryosphaeriaceae species, and in vivo, in grafted plants artificially inoculated with Neofusicoccum parvum and Diplodia seriata. A clear synergistic behavior between chitosan and the two plant extracts has been observed in the mycelial growth inhibition tests (resulting in EC90 values as low as 208 μg·mL−1 for some of the isolates), and statistically significant differences have been found in terms of vascular necroses lengths between treated and non-treated plants, providing further evidence of aforementioned synergism in the case of D. seriata. The reported data supports the possibility of extending the applications of these three basic substances in Viticulture beyond the treatment of mildew.

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