Search Results (5)

Extreme air temperatures along with the synoptic conditions leading to their appearance are examined for the Mediterranean region for the 85-year period of 1940–2024. The data used are daily (04UTC and 12UTC) grid point (1° × 1°) values of 2 m air temperature, 850 hPa air temperature, and 1000 hPa and 500 hPa geopotential heights, obtained from the ERA5 database. For 12UTC and 04UTC, the 2 m air temperature anomalies are calculated and are used for the definition of Extremely High Temperature Days (EHTDs) and Extremely Low Temperature Days (ELTDs), respectively. Overall, 3787 EHTDs and 4872 ELTDs are defined. It is found that EHTDs are evidently more frequent in recent years (increased by 305% since the 1980s) whereas ELTDs are less frequent (decreased by 41% since the 1980s), providing a clear sign of warming of the Mediterranean climate. A multivariate statistical analysis combining factor analysis and k-means clustering, known as spectral clustering, is applied to the data resulting in the definition of nine EHTD and seven ELTD clusters. EHTDs are mainly associated with intense solar heating, blocking anticyclones and warm air advection. ELTDs are connected to intense radiative cooling of the Earth’s surface, cold air advection and Arctic outbreaks. This is a unique study for the Mediterranean region utilizing the high-resolution ERA5 data collected since the 1940s to define and investigate the variability of both high and low temperature extremes using a validated methodology. Full article

ELTD1 is expressed in endothelial and vascular smooth muscle cells and has a role in angiogenesis. It has been classified as an adhesion GPCR, but as yet, no ligand has been identified and its function remains unknown. To establish its role, ELTD1 was overexpressed in endothelial cells. Expression and consequently ligand independent activation of ELTD1 results in endothelial-mesenchymal transistion (EndMT) with a loss of cell-cell contact, formation of stress fibres and mature focal adhesions and an increased expression of smooth muscle actin. The effect was pro-angiogenic, increasing Matrigel network formation and endothelial sprouting. RNA-Seq analysis after the cells had undergone EndMT revealed large increases in chemokines and cytokines involved in regulating immune response. Gene set enrichment analysis of the data identified a number of pathways involved in myofibroblast biology suggesting that the endothelial cells had undergone a type II EMT. This type of EMT is involved in wound repair and is closely associated with inflammation implicating ELTD1 in these processes. Full article

The epidermal growth factor, latrophilin, and seven transmembrane domain–containing protein 1 (ELTD1), is a member of the G–protein coupled receptors (GPCRs) superfamily. Although discovered in 2001, ELTD1 has been investigated only by a few research groups, and important data about its role in normal and tumor cells is still missing. Even though its functions and structure are not yet fully understood, recent studies show that ELTD1 has a role in both physiological and pathological angiogenesis, and it appears to be a very important biomarker and a molecular target in cancer diseases. Upregulation of ELTD1 in malignant cells has been reported, and correlated with poor cancer prognosis. This review article aims to compile the existing data and to discuss the current knowledge on ELTD1 structure and signaling, and its role in physiological and neoplastic conditions. Full article

Adhesion G Protein-Coupled Receptor L4 (ADGRL4/ELTD1) is an endothelial cell adhesion G protein-coupled receptor (aGPCR) which regulates physiological and tumour angiogenesis, providing an attractive target for anti-cancer therapeutics. To date, ADGRL4/ELTD1′s full role and mechanism of function within endothelial biology remains unknown, as do its ligand(s). In this study, ADGRL4/ELTD1 silencing, using two independent small interfering RNAs (siRNAs), was performed in human umbilical vein endothelial cells (HUVECS) followed by transcriptional profiling, target gene validation, and metabolomics using liquid chromatography-mass spectrometry in order to better characterise ADGRL4/ELTD1′s role in endothelial cell biology. We show that ADGRL4/ELTD1 silencing induced expression of the cytoplasmic metabolic regulator ATP Citrate Lyase (ACLY) and the mitochondria-to-cytoplasm citrate transporter Solute Carrier Family 25 Member 1 (SLC25A1) but had no apparent effect on pathways downstream of ACLY (fatty acid and cholesterol synthesis or acetylation). Silencing induced KIT expression and affected the Notch signalling pathway, upregulating Delta Like Canonical Notch Ligand 4 (DLL4) and suppressing Jagged Canonical Notch Ligand 1 (JAG1) and Hes Family BHLH Transcription Factor 2 (HES2). The effect of ADGRL4/ELTD1 silencing on the cellular metabolic profile was modest but several metabolites were significantly affected. Cis-aconitic acid, uridine diphosphate (UDP)-glucoronate, fructose 2,6-diphosphate, uridine 5-diphosphate, and aspartic acid were all elevated as a result of silencing and phosphocreatine, N-acetylglutamic acid, taurine, deoxyadenosine triphosphate, and cytidine monophosphate were depleted. Metabolic pathway analysis implicated ADGRL4/ELTD1 in pyrimidine, amino acid, and sugar metabolism. In summary, this study shows that ADGRL4/ELTD1 impacts core components of endothelial metabolism and regulates genes involved in endothelial differentiation/homeostasis and Notch signalling. Full article

Glioblastoma, the most common primary brain tumor, has few available therapies providing significant improvement in survival. Molecular signatures associated with tumor aggressiveness as well as with disease progression and their relation to differences in signaling pathways implicated in gliomagenesis have recently been described. A number of biomarkers which have potential in diagnosis, prognosis and prediction of response to therapy have been identified and along with imaging modalities could contribute to the clinical management of GBM. Molecular biomarkers including O(6)-methlyguanine-DNA-methyltransferase (MGMT) promoter and deoxyribonucleic acid (DNA) methylation, loss of heterozygosity (LOH) of chromosomes 1p and 19q, loss of heterozygosity 10q, isocitrate dehydrogenase (IDH) mutations, epidermal growth factor receptor (EGFR), epidermal growth factor, latrophilin, and 7 transmembrane domain-containing protein 1 on chromosome 1 (ELTD1), vascular endothelial growth factor (VEGF), tumor suppressor protein p53, phosphatase and tensin homolog (PTEN), p16INK4a gene, cytochrome c oxidase (CcO), phospholipid metabolites, telomerase messenger expression (hTERT messenger ribonucleic acid [mRNA]), microRNAs (miRNAs), cancer stem cell markers and imaging modalities as potential biomarkers are discussed. Inclusion of emerging biomarkers in prospective clinical trials is warranted in an effort for more effective personalized therapy in the future. Full article