IRF3 regulates neuroinflammatory responses and the expression of genes associated with Alzheimer's disease.

The pathological role of interferon signaling is emerging in neuroinflammatory disorders, yet, the specific role of Interferon Regulatory Factor 3 (IRF3) in neuroinflammation remains poorly understood. Here, we show that global IRF3 deficiency delays TLR4-mediated signaling in microglia and attenuates the hallmark features of LPS-induced inflammation such as cytokine release, microglial reactivity, astrocyte activation, myeloid cell infiltration, and inflammasome activation. Moreover, expression of a constitutively active IRF3 (S388D/S390D:IRF3-2D) in microglia induces a transcriptional program reminiscent of the Activated Response Microglia and the expression of genes associated with Alzheimer's Disease, notably apolipoprotein-e. Lastly, using bulk-RNAseq of IRF3-2D brain myeloid cells, we identified Z-DNA binding protein-1 as a target of IRF3 that is relevant across various neuroinflammatory disorders. Together, our results identify IRF3 as an important regulator of LPS-mediated neuroinflammatory responses and highlight IRF3 as a central regulator of disease-specific gene activation in different neuroinflammatory diseases

The impact of gender-role-orientations on subjective career success: a multilevel study of 36 societies

International audienceWe investigate the relationships between gender-role-orientation (i.e., androgynous, masculine, feminine and undifferentiated) and subjective career success among business professionals from 36 societies. Drawing on the resource management perspective, we predict that androgynous individuals will report the highest subjective career success, followed by masculine, feminine, and undifferentiated individuals. We also postulate that meso-organizational culture and macro-societal values will have moderating effects on gender role's impact on subjective career success. The results of our hierarchical linear models support the hypothesized hierarchy of the relationships between gender-role-orientations and subjective career success. However, we found that ethical achievement values at the societal culture level was the only variable that had a positive moderating impact on the relationship between feminine orientation and subjective career success. Thus, our findings of minimal moderation effect suggest that meso- and macro-level environments may not play a significant role in determining an individual's perception of career success

Experimental Assessment of the Water Quality Influence on the Phosphorus Uptake of an Invasive Aquatic Plant: Biological Responses throughout Its Phenological Stage

International audienceUnderstanding how an invasive plant can colonize a large range of environments is still a great challenge in freshwater ecology. For the first time, we assessed the relative importance of four factors on the phosphorus uptake and growth of an invasive macrophyte Elodea nuttallii (Planch.) St. John. This study provided data on its phenotypic plasticity, which is frequently suggested as an important mechanism but remains poorly investigated. The phosphorus uptake of two Elodea nuttallii subpopulations was experimentally studied under contrasting environmental conditions. Plants were sampled in the Rhine floodplain and in the Northern Vosges mountains, and then maintained in aquaria in hard (Rhine) or soft (Vosges) water. Under these conditions, we tested the influence of two trophic states (eutrophic state, 100 mu g.l(-1) P-PO43- and hypertrophic state, 300 mu g.l(-1) P-PO43-) on the P metabolism of plant subpopulations collected at three seasons (winter, spring and summer). Elodea nuttallii was able to absorb high levels of phosphorus through its shoots and enhance its phosphorus uptake, continually, after an increase of the resource availability (hypertrophic > eutrophic). The lowest efficiency in nutrient use was observed in winter, whereas the highest was recorded in spring, what revealed thus a storage strategy which can be beneficial to new shoots. This experiment provided evidence that generally, the water trophic state is the main factor governing P uptake, and the mineral status (softwater > hardwater) of the stream water is the second main factor. The phenological stage appeared to be a confounding factor to P level in water. Nonetheless, phenology played a role in P turnover in the plant. Finally, phenotypic plasticity allows both subpopulations to adapt to a changing environment

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Recent trends and outlook of the Spanish energy system

During the last decades the Spanish energy system has become more energy and carbon intensive, and more dependent on external energy resources, although this trend seems to have stopped in the recent years. The regulation of the electricity and gas markets has significantly changed. Two scenarios for the 2030 time horizon are analysed with the POLES-Spain energy model. Under the baseline scenario, the main energy challenges persist even if the energy-GDP intensity reverses its increasing trend. According to a second scenario that assumes significant progress in energy efficiency and higher international energy prices, the energy system undergoes a transformation towards cleaner technologies and renewable energy resources.JRC.DG.J.2-The economics of climate change, energy and transpor

The impact of gender role orientations on subjective career success: A multi-level study of 36 societies

We investigate the relationships between gender-role-orientation (i.e., androgynous, masculine, feminine and undifferentiated) and subjective career success among business professionals from 36 societies. Drawing on the resource management perspective, we predict that androgynous individuals will report the highest subjective career success, followed by masculine, feminine, and undifferentiated individuals. We also postulate that meso-organizational culture and macro-societal values will have moderating effects on gender role's impact on subjective career success. The results of our hierarchical linear models support the hypothesized hierarchy of the relationships between gender-role-orientations and subjective career success. However, we found that ethical achievement values at the societal culture level was the only variable that had a positive moderating impact on the relationship between feminine orientation and subjective career success. Thus, our findings of minimal moderation effect suggest that meso- and macro-level environments may not play a significant role in determining an individual's perception of career success

The impact of gender-role-orientations on subjective career success: A multilevel study of 36 societies

We investigate the relationships between gender-role-orientation (i.e., androgynous, masculine, feminine and undifferentiated) and subjective career success among business professionals from 36 societies. Drawing on the resource management perspective, we predict that androgynous individuals will report the highest subjective career success, followed by masculine, feminine, and undifferentiated individuals. We also postulate that meso-organizational culture and macro-societal values will have moderating effects on gender role's impact on subjective career success. The results of our hierarchical linear models support the hypothesized hierarchy of the relationships between gender-role-orientations and subjective career success. However, we found that ethical achievement values at the societal culture level was the only variable that had a positive moderating impact on the relationship between feminine orientation and subjective career success. Thus, our findings of minimal moderation effect suggest that meso- and macro-level environments may not play a significant role in determining an individual's perception of career success. © 2022 Elsevier Inc