Origin and Evolution of TRIM Proteins: New Insights from the Complete TRIM Repertoire of Zebrafish and Pufferfish

Tripartite motif proteins (TRIM) constitute a large family of proteins containing a RING-Bbox-Coiled Coil motif followed by different C-terminal domains. Involved in ubiquitination, TRIM proteins participate in many cellular processes including antiviral immunity. The TRIM family is ancient and has been greatly diversified in vertebrates and especially in fish. We analyzed the complete sets of trim genes of the large zebrafish genome and of the compact pufferfish genome. Both contain three large multigene subsets - adding the hsl5/trim35-like genes (hltr) to the ftr and the btr that we previously described - all containing a B30.2 domain that evolved under positive selection. These subsets are conserved among teleosts. By contrast, most human trim genes of the other classes have only one or two orthologues in fish. Loss or gain of C-terminal exons generated proteins with different domain organizations; either by the deletion of the ancestral domain or, remarkably, by the acquisition of a new C-terminal domain. Our survey of fish trim genes in fish identifies subsets with different evolutionary dynamics. trims encoding RBCC-B30.2 proteins show the same evolutionary trends in fish and tetrapods: they evolve fast, often under positive selection, and they duplicate to create multigenic families. We could identify new combinations of domains, which epitomize how new trim classes appear by domain insertion or exon shuffling. Notably, we found that a cyclophilin-A domain replaces the B30.2 domain of a zebrafish fintrim gene, as reported in the macaque and owl monkey antiretroviral TRIM5α. Finally, trim genes encoding RBCC-B30.2 proteins are preferentially located in the vicinity of MHC or MHC gene paralogues, which suggests that such trim genes may have been part of the ancestral MHC

Physico-Chemical Transformation and Toxicity of Multi-Shell InP Quantum Dots under Simulated Sunlight Irradiation, in an Environmentally Realistic Scenario

International audienceQuantum dots (QDs) are widely used in optoelectronics, lighting, and photovoltaics leadingto their potential release into the environment. The most promising alternative to the highly toxiccadmium selenide (CdSe) QDs are indium phosphide (InP) QDs, which show reduced toxicity andcomparable optical and electronic properties. QD degradation leads to the release of toxic metal ionsinto the environment. Coating the QD core with robust shell(s) composed of another semi-conductormaterial enhances their properties and protects the QD from degradation. We recently developeddouble-shelled InP QDs, which proved to be less toxic than single-shell QDs. In the present study,we confirm their reduced cytotoxicity, with an LC50 at 77 nM for pristine gradient shell QDs and>100 nM for pristine thin and thick shell QDs. We also confirm that these three QDs, when exposedto simulated sunlight, show greater cytotoxicity compared to pristine ones, with LC50 ranging from15 to 23 nM. Using a combination of spectroscopic and microscopic techniques, we characterize thedegradation kinetics and transformation products of single- and double-shell QDs, when exposedto solar light at high temperature, simulating environmental conditions. Non-toxic pristine QDsdegrade to form toxic In–phosphate, In–carboxylate, Zn–phosphate, and oxidized Se, all of whichprecipitate as heterogeneous deposits. Comparison of their degradation kinetics highlights that theQDs bearing the thickest ZnS outer shell are, as expected, the most resistant to photodegradationamong the three tested QDs, as gradient shell, thin shell, and thick shell QDs lose their opticalproperties in less than 15 min, 60 min, and more than 90 min, respectively. They exhibit the highestphotoluminescence efficiency, i.e., the best functionality, with a photoluminescence quantum yield inaqueous solution of 24%, as compared to 18% for the gradient shell and thin shell QDs. Therefore,they can be considered as safer-by-design QDs

Strain-specific changes in nucleus accumbens transcriptome and motivation for palatable food reward in mice exposed to maternal separation

International audienceIntroduction In humans, adversity in childhood exerts enduring effects on brain and increases the vulnerability to psychiatric diseases. It also leads to a higher risk of eating disorders and obesity. Maternal separation (MS) in mice has been used as a proxy of stress during infancy. We hypothesized that MS in mice affects motivation to obtain palatable food in adulthood and changes gene expression in reward system. Methods Male and female pups from C57Bl/6J and C3H/HeN mice strains were subjected to a daily MS protocol from postnatal day (PND) 2 to PND14. At adulthood, their motivation for palatable food reward was assessed in operant cages. Results Compared to control mice, male and female C3H/HeN mice exposed to MS increased their instrumental response for palatable food, especially when the effort required to obtain the reward was high. Importantly, this effect is shown in animals fed ad libitum . Transcriptional analysis revealed 375 genes differentially expressed in the nucleus accumbens of male MS C3H/HeN mice compared to the control group, some of these being associated with the regulation of the reward system (e.g., Gnas , Pnoc ). Interestingly, C57Bl/6J mice exposed to MS did not show alterations in their motivation to obtain a palatable reward, nor significant changes in gene expression in the nucleus accumbens. Conclusion MS produces long-lasting changes in motivation for palatable food in C3H/HeN mice, but has no impact in C57Bl/6J mice. These behavioral alterations are accompanied by drastic changes in gene expression in the nucleus accumbens, a key structure in the regulation of motivational processes

Strain-specific changes in nucleus accumbens transcriptome and motivation for food reward in mice exposed to maternal separation

Adversity in childhood exerts enduring effects on brain and increases the vulnerability to psychiatric diseases. It also leads to a higher risk for eating disorders and obesity. We hypothesised that neonatal stress in mice affects motivation to obtain palatable food in adulthood and changes gene expression in reward system. Male and female pups from C57Bl/6J and C3H/HeN mice strains were subjected to a daily maternal separation (MS) protocol from PND2 to PND14. In adulthood, their motivation for palatable food reward was assessed in operant cages. Compared to control mice, male and female C3H/Hen mice exposed to MS significantly did more lever presses to obtain palatable food especially when the effort required to obtain the reward is high. Transcriptional analysis reveals 375 genes differentially expressed in the nucleus accumbens of male MS C3H/HeN mice compared to the control group, some of these being associated with the regulation of the reward system (e.g. Gnas, Pnoc ). Interestingly, C57Bl/6J mice exposed to MS did not show any alteration in their motivation to obtain a palatable reward nor significant changes in gene expression in the nucleus accumbens. In conclusion, neonatal stress produces lasting changes in motivation for palatable food in C3H/HeN offspring but has no impact in C57Bl/6J offspring. These behavioural alterations are accompanied by drastic changes in gene expression specifically within the nucleus accumbens, a key structure in the regulation of motivational processes