Quadratic maps between modules

We introduce a notion of $R$-quadratic maps between modules over a commutative ring $R$ which generalizes several classical notions arising in linear algebra and group theory. On a given module $M$ such maps are represented by $R$-linear maps on a certain module $P^2_R(M)$. The structure of this module is described in term of the symmetric tensor square $Sym^2_R(M)$, the degree 2 component $\Gamma^2_R(M)$ of the divided power algebra over $M$, and the ideal $I_2$ of $R$ generated by the elements $r^2-r$, $r\in R$. The latter is shown to represent quadratic derivations on $R$ which arise in the theory of modules over square rings. This allows to extend the classical notion of nilpotent $R$-group of class 2 with coefficients in a 2-binomial ring $R$ to any ring $R$. We provide a functorial presentation of $I_2$ and several exact sequences embedding the modules $P^2_R(M)$ and $\Gamma^2_R(M)$.Comment: 22 page

Commentary: Anxiety- and Depression-like States Lead to Pronounced Olfactory Deficits and Impaired Adult Neurogenesis in Mice

A commentary on: Anxiety- and Depression-like States Lead to Pronounced Olfactory Deficits and Impaired Adult Neurogenesis in Mice by Siopi, E., Denizet, M., Gabellec, M. M., de Chaumont, F., Olivo-Marin, J. C., Guilloux, J. P., et al. (2016). J. Neurosci. 36, 518–531. doi: 10.1523/JNEUROSCI.2817-15.201

Social influences on microglial reactivity and neuronal damage after cardiac arrest/cardiopulmonary resuscitation

Social isolation presents a risk factor and worsens outcome to cerebrovascular diseases; however, the underlying mechanisms remain underspecified. This study examines the effect of social environment on microglial reactivity after global cerebral ischemia, to test the hypothesis that social isolation leads to greater microglial responses. Adult female and male mice were pair-housed or socially isolated for one week prior to cardiac arrest/cardiopulmonary resuscitation (CA/CPR) or the sham procedure, and following either 2 or 24 hours of reperfusion, microglia samples were enriched and analyzed for gene expression. At the 2-hour time point, microglia from both females and males exhibited ischemia-induced inflammation, characterized by the gene expression increase of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6), regardless of the housing conditions. However, at 24 hours post-ischemia, social housing attenuated microglial pro-inflammatory gene expression in a sex-specific manner. At this time point, the ischemia-induced increased expression of IL-1β and IL-6 was attenuated by social interaction in microglia from male mice, while among female mice social attenuation of the inflammatory response was observed in the microglial expression of cell surface protein major histocompatibility complex II (MHC II). A second study examined behavioral and physiological measures 96 hours after ischemic injury. At this time point, female and male mice displayed increased locomotion and exploratory behavior following CA/CPR relative to controls. Regardless of sex, ischemia also elicited neuroinflammation and neurodegeneration, both of which were modulated by the social environment. Hippocampal nitric oxide (iNOS), cortical TNF-α, and counts of Fluoro-Jade C positive stained cells in the CA1 region of the hippocampus, were increased in the isolated CA/CPR group relative to sham controls and the pair-housed CA/CPR groups. Together, these data indicate that female and male mice exhibit similar outcome measures and social modulation at 96 hours post-ischemic injury, nonetheless, that social environment influences microglial reactivity to global cerebral ischemia in a sex-specific manner

Time-of-Day Dictates Transcriptional Inflammatory Responses to Cytotoxic Chemotherapy

Many cytotoxic chemotherapeutics elicit a proinflammatory response which is often associated with chemotherapy-induced behavioral alterations. The immune system is under circadian influence; time-of-day may alter inflammatory responses to chemotherapeutics. We tested this hypothesis by administering cyclophosphamide and doxorubicin (Cyclo/Dox), a common treatment for breast cancer, to female BALB/c mice near the beginning of the light or dark phase. Mice were injected intravenously with Cyclo/Dox or the vehicle two hours after lights on (zeitgeber time (ZT2), or two hours after lights off (ZT14). Tissue was collected 1, 3, 9, and 24 hours later. Mice injected with Cyclo/Dox at ZT2 lost more body mass than mice injected at ZT14. Cyclo/Dox injected at ZT2 increased the expression of several pro-inflammatory genes within the spleen; this was not evident among mice treated at ZT14. Transcription of enzymes within the liver responsible for converting Cyclo/Dox into their toxic metabolites increased among mice injected at ZT2; furthermore, transcription of these enzymes correlated with splenic pro-inflammatory gene expression when treatment occurred at ZT2 but not ZT14. The pattern was reversed in the brain; pro-inflammatory gene expression increased among mice injected at ZT14. These data suggest that inflammatory responses to chemotherapy depend on time-of-day and are tissue specific

Low Sucrose, Omega-3 Enriched Diet Has Region-Specific Effects on Neuroinflammation and Synaptic Function Markers in a Mouse Model of Doxorubicin-Based Chemotherapy

Chemotherapeutic agents such as doxorubicin may negatively affect long-term brain functioning in cancer survivors; neuroinflammation may play a causal role. Dietary approaches that reduce inflammation, such as lowering sucrose and increasing eicosapentaenoic acid plus docosahexaenoic acid (EPA + DHA), may attenuate chemotherapy-induced neuroinflammation and synaptic damage, thereby improving quality of life. Ovariectomized, C57BL/6 mice were assigned to a chemotherapy (9 mg/kg doxorubicin + 90 mg/kg cyclophosphamide) or vehicle two-injection regimen, with injections two and four weeks after starting diets. In Study 1, mice received low sucrose diets with EPA + DHA or No EPA + DHA for four to six weeks; tissues were collected four, seven, or 14 days after the second injection. Compared to vehicle, chemotherapy increased pro-inflammatory cytokine IL-1β at day seven in the cortex and hippocampus, and reduced gene expression of synaptic marker Shank 3 at all timepoints in cortex, while EPA + DHA increased expression of Shank 3. In Study 2, high or low sucrose/EPA + DHA or No EPA + DHA diets were fed for five weeks; tissues were collected ten days after the second injection. Among chemotherapy-treated mice, brain DHA was higher with low sucrose feeding. Furthermore, low sucrose increased gene expression of Shank 1, while EPA + DHA increased expression of Shank 3 and reduced protein concentrations of pro-inflammatory markers IL-5, IL-6 and KC/GRO in the cortex, but not the hippocampus. Low sucrose, EPA + DHA diets may attenuate neuroinflammation and synaptic damage induced by doxorubicin-based chemotherapy in specific brain regions

Low Sucrose, Omega-3 Enriched Diet Has Region-Specific Effects on Neuroinflammation and Synaptic Function Markers in a Mouse Model of Doxorubicin-Based Chemotherapy

Chemotherapeutic agents such as doxorubicin may negatively affect long-term brain functioning in cancer survivors; neuroinflammation may play a causal role. Dietary approaches that reduce inflammation, such as lowering sucrose and increasing eicosapentaenoic acid plus docosahexaenoic acid (EPA + DHA), may attenuate chemotherapy-induced neuroinflammation and synaptic damage, thereby improving quality of life. Ovariectomized, C57BL/6 mice were assigned to a chemotherapy (9 mg/kg doxorubicin + 90 mg/kg cyclophosphamide) or vehicle two-injection regimen, with injections two and four weeks after starting diets. In Study 1, mice received low sucrose diets with EPA + DHA or No EPA + DHA for four to six weeks; tissues were collected four, seven, or 14 days after the second injection. Compared to vehicle, chemotherapy increased pro-inflammatory cytokine IL-1β at day seven in the cortex and hippocampus, and reduced gene expression of synaptic marker Shank 3 at all timepoints in cortex, while EPA + DHA increased expression of Shank 3. In Study 2, high or low sucrose/EPA + DHA or No EPA + DHA diets were fed for five weeks; tissues were collected ten days after the second injection. Among chemotherapy-treated mice, brain DHA was higher with low sucrose feeding. Furthermore, low sucrose increased gene expression of Shank 1, while EPA + DHA increased expression of Shank 3 and reduced protein concentrations of pro-inflammatory markers IL-5, IL-6 and KC/GRO in the cortex, but not the hippocampus. Low sucrose, EPA + DHA diets may attenuate neuroinflammation and synaptic damage induced by doxorubicin-based chemotherapy in specific brain regions

Mammary Tumors Induce Central Pro-inflammatory Cytokine Expression, but Not Behavioral Deficits in Balb/C Mice

Breast cancer survivors are more likely to develop mood disorders and cognitive deficits than women in the general population. Previous studies suggest that peripheral tumors elicit central pro-inflammatory cytokine production, in turn leading to depression and cognitive deficits. In the current study, two cohorts of female Balb/C mice received bilateral orthotopic injections of syngeneic 67NR, 4T07, or 4T1cells (1 x 10(5) cells per injection) to induce mammary tumors. Approximately three weeks later, learned fear (via fear conditioning) or depressive-like behavior (via tail suspension and forced swim test) was assessed. Proinflammatory cytokine levels were increased in the serum (IL-1beta, TNFalpha, IFNgamma) and livers (IL-1beta, IL-6, TNFalpha) of mice with 4T07 or 4T1 tumors compared to 67NR tumors and the vehicle control. IL-1beta was increased in both the hippocampus and cortex of mice injected with 4T07 or 4T1 cell lines relative to the other treatment groups. However, mammary tumors had no effect on hippocampal doublecortin + and did not alter depressive-like behavior or learned fear. These data demonstrate that similarly sized tumors can produce differential immune responses and that tumor-induced central pro-inflammatory cytokine production can exist in the absence of depressive-like behavior or cognitive deficits

Cryo-EM structure of a helicase loading intermediate containing ORC-Cdc6-Cdt1-MCM2-7 bound to DNA

In eukaryotes, the Cdt1-bound replicative helicase core MCM2-7 is loaded onto DNA by the ORC-Cdc6 ATPase to form a prereplicative complex (pre-RC) with an MCM2-7 double hexamer encircling DNA. Using purified components in the presence of ATP-γS, we have captured in vitro an intermediate in pre-RC assembly that contains a complex between the ORC-Cdc6 and Cdt1-MCM2-7 heteroheptamers called the OCCM. Cryo-EM studies of this 14-subunit complex reveal that the two separate heptameric complexes are engaged extensively, with the ORC-Cdc6 N-terminal AAA+ domains latching onto the C-terminal AAA+ motor domains of the MCM2-7 hexamer. The conformation of ORC-Cdc6 undergoes a concerted change into a right-handed spiral with helical symmetry that is identical to that of the DNA double helix. The resulting ORC-Cdc6 helicase loader shows a notable structural similarity to the replication factor C clamp loader, suggesting a conserved mechanism of action

Development of a new bench for puncturing of irradiated fuel rods in STAR hot laboratory

A new device for puncturing of irradiated fuel rods in commercial power plants has been designed by Fuel Research Department of CEA Cadarache in order to provide experimental data of high precision on fuel pins with various designs. It will replace the current set-up that has been used since 1998 in hot cell 2 of STAR facility with more than 200 rod puncturing experiments. Based on this consistent experimental feedback, the heavy-duty technique of rod perforation by clad punching has been preserved for the new bench. The method of double expansion of rod gases is also retained since it allows upgrading the confidence interval of volumetric results obtained from rod puncturing. Furthermore, many evolutions have been introduced in the new design in order to improve its reliability, to make the maintenance easier by remote handling and to reduce experimental uncertainties. Tightness components have been studied with Sealing Laboratory Maestral at Pierrelatte so as to make them able to work under mixed pressure conditions (from vacuum at 10-5 mbar up to pressure at 50 bars) and to lengthen their lifetime under permanent gamma irradiation in hot cell. Bench ergonomics has been optimized to make its operating by remote handling easier and to secure the critical phases of a puncturing experiment. A high pressure gas line equipped with high precision pressure sensors out of cell can be connected to the bench in cell for calibration purposes. Uncertainty analyses using Monte Carlo calculations have been performed in order to optimize capacity of the different volumes of the apparatus according to volumetric characteristics of the rod to be punctured. At last this device is composed of independent modules which allow puncturing fuel pins out of different geometries (PWR, BWR, VVER). After leak tests of the device and remote handling simulation in a mock-up cell, several punctures of calibrated specimens have been performed in 2016. The bench will be implemented soon in hot cell 2 of STAR facility for final qualification tests. PWR rod punctures are already planned for 2018