IRS-4 mediated mitogenic signalling by insulin and growth hormone in LB cells,a murine T-cell lymphoma devoid of IGF-I receptors

Insulin and growth hormone (GH) induce mitogenic and metabolic signals in cells, GH either directly or indirectly via IGF-I production. We have studied a spontaneous murine T-cell lymphoma (LB cells) devoid of IGF-1 receptors in which proliferation is maintained by insulin [Int. J. Cancer 50 (1992) 80], and show that GH is more potent than insulin, with both GH and insulin dose-response curves for thymidine incorporation being bell-shaped. Binding showed somatogenic rather than lactogenic GH receptors. Insulin stimulated phosphorylation of the insulin receptor and of a 160-kDa protein, identified as the IRS-4 protein. This phosphorylated IRS-4 associated with PI3-kinase, which was activated along with the downstream p70(S6) kinase, whereas the Ras-MAPK pathway was not. Using selective inhibitors, the PI3-kinase, but not p70(S6) kinase or MEK, was found to be involved in insulin-stimulated DNA synthesis. GH induced tyrosine phosphorylation of IRS-4 and nuclear translocation of STAT5. The LB cells constitute a new model for studying GH and insulin signalling without interference of IGF-1 receptors.     

Design and synthesis of 3-phenyl tetrahydronaphthalenic derivatives as new selective MT2 melatoninergic ligands

Tetrahydronaphthalenic analogues of melatonin have been synthesized and evaluated as melatonin receptor ligands. Introduction of a phenyl substituent in the 3-position of the tetraline ring allows to obtain MT(2) selective ligands. Activity and MT(2) selectivity can be modulated with suitable modifications of the N-acyl substituent. The (+)-(RR)-cis enantiomer of the N-[2-(7-methoxy-3-phenyl-1,2,3,4-tetrahydro-naphthalen-1-yl)ethyl]cyclobutyl carboxamide (14) is one of the most MT(2) selective ligands described until now and behaves as an antagonist.     

Critical residues for RNA discrimination of the histone hairpin binding protein (HBP) investigated by the yeast three-hybrid system

The histone hairpin binding protein (HBP, also called SLBP, which stands for stem-loop binding protein) binds specifically to a highly conserved hairpin structure located in the 3' UTR of the cell-cycle-dependent histone mRNAs. HBP consists of a minimal central RNA binding domain (RBD) flanked by an N- and C-terminal domain. The yeast three-hybrid system has been used to investigate the critical residues of the human HBP involved in the binding of its target hairpin structure. By means of negative selections followed by positive selections, we isolated mutant HBP species. Our results indicate tight relationships between the RBD and the N- and C-terminal domains.     

Migration patterns and navigation cues of Atlantic salmon post-smolts migrating from 12 rivers through the coastal zones around the Irish Sea

The freshwater phase of the first seaward migration of juvenile Atlantic salmon (Salmo salar) is relatively well understood when compared with our understanding of the marine phase of their migration. In 2021, 1008 wild and 60 ranched Atlantic salmon smolts were tagged with acoustic transmitters in 12 rivers in England, Scotland, Northern Ireland and Ireland. Large marine receiver arrays were deployed in the Irish Sea at two locations: at the transition of the Irish Sea into the North Atlantic between Ireland and Scotland, and between southern Scotland and Northern Ireland, to examine the early phase of the marine migration of Atlantic salmon smolts. After leaving their natal rivers' post-smolt migration through the Irish Sea was rapid with minimum speeds ranging from 14.03 to 38.56 km.day⁻¹ for Atlantic salmon smolts that entered the Irish Sea directly from their natal river, to 9.69–39.94 km.day⁻¹ for Atlantic salmon smolts that entered the Irish Sea directly from their natal estuary. Population minimum migration success through the study area was strongly correlated with the distance of travel, populations further away from the point of entry to the open North Atlantic exhibited lower migration success. Post-smolts from different populations experienced different water temperatures on entering the North Atlantic. This was largely driven by the timing of their migration and may have significant consequences for feeding and ultimately survivorship. The influence of water currents on post-smolt movement was investigated using data from previously constructed numerical hydrodynamic models. Modeled water current data in the northern Irish Sea showed that post-smolts had a strong preference for migrating when the current direction was at around 283° (west-north-west) but did not migrate when exposed to strong currents in other directions. This is the most favorable direction for onward passage from the Irish Sea to the continental shelf edge current, a known accumulation point for migrating post-smolts. These results strongly indicate that post-smolts migrating through the coastal marine environment are: (1) not simply migrating by current following (2) engage in active directional swimming (3) have an intrinsic sense of their migration direction and (4) can use cues other than water current direction to orientate during this part of their migration.     

Immunological memory within the innate immune system

Immune memory has traditionally been the domain of the adaptive immune system, present only in antigen‐specific T and B cells. The purpose of this review is to summarize the evidence for immunological memory in lower organisms (which are not thought to possess adaptive immunity) and within specific cell subsets of the innate immune system. A special focus will be given to recent findings in both mouse and humans for specificity and memory in natural killer (NK) cells, which have resided under the umbrella of innate immunity for decades. The surprising longevity and enhanced responses of previously primed NK cells will be discussed in the context of several immunization settings.     

Kidney cancer mortality and ionizing radiation among French and German uranium miners

The investigation of potential adverse health effects of occupational exposures to ionizing radiation, on uranium miners, is an important area of research. Radon is a well-known carcinogen for lung, but the link between radiation exposure and other diseases remains controversial, particularly for kidney cancer. The aims of this study were therefore to perform external kidney cancer mortality analyses and to assess the relationship between occupational radiation exposure and kidney cancer mortality, using competing risks methodology, from two uranium miners cohorts. The French (n = 3,377) and German (n = 58,986) cohorts of uranium miners included 11 and 174 deaths from kidney cancer. For each cohort, the excess of kidney cancer mortality has been assessed by standardized mortality ratio (SMR) corrected for the probability of known causes of death. The associations between cumulative occupational radiation exposures (radon, external gamma radiation and long-lived radionuclides) or kidney equivalent doses and both the cause-specific hazard and the probability of occurrence of kidney cancer death have been estimated with Cox and Fine and Gray models adjusted to date of birth and considering the attained age as the timescale. No significant excess of kidney cancer mortality has been observed neither in the French cohort (SMR = 1.49, 95 % confidence interval [0.73; 2.67]) nor in the German cohort (SMR = 0.91 [0.77; 1.06]). Moreover, no significant association between kidney cancer mortality and any type of occupational radiation exposure or kidney equivalent dose has been observed. Future analyses based on further follow-up updates and/or large pooled cohorts should allow us to confirm or not the absence of association.     

Graph analysis of functional brain networks: practical issues in translational neuroscience

The brain can be regarded as a network: a connected system where nodes, or units, represent different specialized regions and links, or connections, represent communication pathways. From a functional perspective, communication is coded by temporal dependence between the activities of different brain areas. In the last decade, the abstract representation of the brain as a graph has allowed to visualize functional brain networks and describe their non-trivial topological properties in a compact and objective way. Nowadays, the use of graph analysis in translational neuroscience has become essential to quantify brain dysfunctions in terms of aberrant reconfiguration of functional brain networks. Despite its evident impact, graph analysis of functional brain networks is not a simple toolbox that can be blindly applied to brain signals. On the one hand, it requires the know-how of all the methodological steps of the pipeline that manipulate the input brain signals and extract the functional network properties. On the other hand, knowledge of the neural phenomenon under study is required to perform physiologically relevant analysis. The aim of this review is to provide practical indications to make sense of brain network analysis and contrast counterproductive attitudes.