High expression of CXCR4 may predict poor survival in resected pancreatic adenocarcinoma

Chemokines and their receptors are involved in tumourigenicity and clinicopathological significance of chemokines receptor expression in pancreatic adenocarcinoma (PA) is not fully understood. This study was conducted to determine patients' outcome according to the expressions of CXCR4, CXCR7 and HIF-1α after resection of PA. Immunohistochemistry for CXCR4, CXCR7 and HIF-1α expressions as well as cell proliferative index (Ki-67) was conducted in 71 resected (R0) PA and their 48 related lymph nodes (LN) using tissue microarray. CXCR4 and CXCR7 expressions were positively correlated to HIF-1α suggesting a potential role of HIF-1α in CXCR4 and CXCR7 transcription activation. Patients with CXCR4high tumour expression had shorter OS than those with low expression (median survival: 9.7 vs 43.2 months, P=0.0006), a higher risk of LN metastases and liver recurrence. In multivariate analysis, high CXCR4 expression, LN metastases and poorly differentiated tumour are independent negative prognosis factors. In a combining analysis, patients with CXCR4low/CXCR7low tumour had a significantly shorter DFS and OS than patients with a CXCR7high/CXCR4high tumour. CXCR4 in resected PA may represent a valuable prognostic factor as well as an attractive target for therapeutic purpose

Rapid evolution of thermal tolerance in the water flea Daphnia

Global climate is changing rapidly, and the degree to which natural populations respond genetically to these changes is key to predicting ecological responses1, 2, 3. So far, no study has documented evolutionary changes in the thermal tolerance of natural populations as a response to recent temperature increase. Here, we demonstrate genetic change in the capacity of the water flea Daphnia to tolerate higher temperatures using both a selection experiment and the reconstruction of evolution over a period of forty years derived from a layered dormant egg bank. We observed a genetic increase in thermal tolerance in response to a two-year ambient +4 °C selection treatment and in the genotypes of natural populations from the 1960s and 2000s hatched from lake sediments. This demonstrates that natural populations have evolved increased tolerance to higher temperatures, probably associated with the increased frequency of heat waves over the past decades, and possess the capacity to evolve increased tolerance to future warming

Glucocorticoid receptor isoforms direct distinct mitochondrial programs to regulate ATP production

The glucocorticoid receptor (GR), a nuclear receptor and major drug target, has a highly conserved minor splice variant, GRγ, which differs by a single arginine within the DNA binding domain. GRγ, which comprises 10% of all GR transcripts, is constitutively expressed and tightly conserved through mammalian evolution, suggesting an important non-redundant role. However, to date no specific role for GRγ has been reported. We discovered significant differences in subcellular localisation, and nuclear-cytoplasmic shuttling in response to ligand. In addition the GRγ transcriptome and protein interactome was distinct, and with a gene ontology signal for mitochondrial regulation which was confirmed using Seahorse technology. We propose that evolutionary conservation of the single additional arginine in GRγ is driven by a distinct, non-redundant functional profile, including regulation of mitochondrial function

ANALYSIS OF ILLICIT DRUGS IN HUMAN BIOLOGICAL SAMPLES BY LC-MSn

There are several classes of illegal substances with different psychotropic effects. It is possible to select a biological matrix and a suitable analytical strategy depending on the aim of the analysis and/or on the availability of the sample or on which kind of information is needed. Liquid chromatography–mass spectrometry (LC-MS or LC-MS/MS) has provided a helpful tool in this field especially for hydrophilic, thermolabile, and nonvolatile analytes, which analysis is sometimes critical by gas chromatography–mass spectrometry (GC-MS). Specific guidelines or procedures have been adopted in order to assist the chemist and to direct him/her towards the practical applications, for which a new analytical method is being created, including measures of verification and external assessment. [...