Severity: Warning
Message: fopen(/var/lib/php/sessions/ci_session76u4e29hv3is27kb8cqois6ehehqikn6): Failed to open stream: No space left on device
Filename: drivers/Session_files_driver.php
Line Number: 177
Backtrace:
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)
Filename: Session/Session.php
Line Number: 137
Backtrace:
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Undefined array key "choices"
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: 8192
Message: strpos(): Passing null to parameter #1 ($haystack) of type string is deprecated
Filename: models/Detail_model.php
Line Number: 71
Backtrace:
File: /var/www/html/application/models/Detail_model.php
Line: 71
Function: strpos
File: /var/www/html/application/controllers/Detail.php
Line: 252
Function: insertAPISummary
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: 8192
Message: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated
Filename: helpers/my_audit_helper.php
Line Number: 8919
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 8919
Function: str_replace
File: /var/www/html/application/controllers/Detail.php
Line: 255
Function: formatAIDetailSummary
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Undefined array key "choices"
Filename: controllers/Detail.php
Line Number: 256
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 256
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 256
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Undefined array key "usage"
Filename: controllers/Detail.php
Line Number: 257
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 257
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Undefined array key "usage"
Filename: controllers/Detail.php
Line Number: 258
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 258
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Undefined array key "usage"
Filename: controllers/Detail.php
Line Number: 259
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 259
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 259
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 259
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Undefined array key "usage"
Filename: controllers/Detail.php
Line Number: 260
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 260
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 260
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Retrotransposons such as LINE-1 and Alu comprise >25% of the human genome. While global hypomethylation of these elements has been widely reported in solid tumours, their epigenetic dysregulation is yet to be characterised in chronic lymphocytic leukaemia, and there has been scant consideration of their evolutionary history that mediates sensitivity to hypomethylation. Here, we developed an approach for locus- and evolutionary subfamily-specific analysis of retrotransposons using the Illumina Infinium Human Methylation 450K microarray platform, which we applied to publicly-available datasets from chronic lymphocytic leukaemia and other haematological malignancies. We identified 9,797 microarray probes mapping to 117 LINE-1 subfamilies and 13,130 mapping to 37 Alu subfamilies. Of these, 10,782 were differentially methylated (PFDR<0.05) in chronic lymphocytic leukaemia patients (n=139) compared with healthy individuals (n=14), with enrichment at enhancers (p=0.002). Differential methylation was associated with evolutionary age of LINE-1 (r2=0.31, p=0.003) and Alu (r2=0.74, p=0.002) elements, with greater hypomethylation of older subfamilies (L1M, AluJ). Locus-specific hypomethylation was associated with differential expression of proximal genes, including DCLK2, HK1, ILRUN, TANK, TBCD, TNFRSF1B and TXNRD2, with higher expression of DCLK2 and TNFRSF1B associated with reduced patient survival. Hypomethylation at nine loci was highly frequent in chronic lymphocytic leukaemia (>90% patients) but not observed in healthy individuals or other leukaemias, and was detectable in blood samples taken prior to chronic lymphocytic leukaemia diagnosis in 9 of 82 individuals from the Melbourne Collaborative Cohort Study. Our results demonstrate differential methylation of retrotransposons in chronic lymphocytic leukaemia by their evolutionary heritage that modulates expression of proximal genes.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7776340 | PMC |
http://dx.doi.org/10.3324/haematol.2019.228478 | DOI Listing |
Autoimmun Rev
December 2024
APC Microbiome Ireland, University College Cork, Ireland; College of Medicine and Health, University College Cork, Ireland.
T helper (Th) 17 and regulatory T (Treg) cells are highly plastic CD4 Th cell subsets, being able not only to actively adapt to their microenvironment, but also to interconvert, acquiring mixed identity markers. These phenotypic changes are underpinned by transcriptional control mechanisms, chromatin reorganization events and epigenetic modifications, that can be hereditable and stable over time. The Ikaros family of transcription factors have a predominant role in T cell subset specification through mechanisms of transcriptional program regulation that enable phenotypical diversification.
View Article and Find Full Text PDFMol Med Rep
March 2025
Key Laboratory for Experimental Teratology of Ministry of Education, Department of Histology and Embryology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China.
Endometriosis (EM) is a chronic inflammatory disease that is one of the most common causes of gynecological systemic lesions in women before menopause. The most representative histological feature of EM is that the endometrium appears outside of the uterine cavity, often in the ovary. Although it is generally accepted that the epithelial and stromal cells of the ectopic endometrium are not malignant, they still have numerous similarities to malignant tumors, including considerable changes to the immune microenvironment (immune monitoring disorder), the creation of a specific hormone environment, high levels of oxidative stress, chronic inflammation and abnormal immune cell regulation.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians University, Munich, Germany.
CD8+ T cells are crucial cytotoxic components of the tumor immune system. In chronic inflammation, they become low-responsive, a state known as T cell exhaustion (TEX). The aim of immune checkpoint blockade is to counteract TEX, yet its dynamics in breast cancer remain poorly understood.
View Article and Find Full Text PDFFront Cell Infect Microbiol
December 2024
Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
In the context of chronic hepatitis B virus (HBV) infection, the continuous replication of HBV within host hepatocytes is a characteristic feature. Rather than directly causing hepatocyte destruction, this replication leads to immune dysfunction and establishes a state of T-B immune tolerance. Successful clearance of the HBV virus is dependent on the close collaboration between humoral and cellular immunity.
View Article and Find Full Text PDFJHEP Rep
January 2025
Hepatitis Viruses and Pathobiology of Chronic Liver Diseases - LabEx DEVweCAN, Inserm U1052, Cancer Research Centre of Lyon - Hepatology Institute of Lyon F - IHU EVEREST, University of Lyon 1, ISPB, France, CNRS UMR5286, Centre Léon, Lyon, France.
Background & Aims: Owing to unexplained interpatient variation and treatment failure in hepatocellular carcinoma (HCC), novel therapeutic approaches remain an urgent clinical need. Hepatic neurons, belonging to the autonomic nervous system (ANS), mediate liver/whole body crosstalk. Pathological innervation of the ANS has been identified in cancer, nurturing tumor stroma and conferring stronger carcinogenic properties.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!