Des ressources végétales endémiques pour optimiser durablement les opérations de réhabilitation du couvert forestier en milieu méditerranéen et tropical : exemple des plantes facilitatrices vectrices de propagation des champignons mycorhiziens

The overexploitation of natural resources, resulting in an increased need for arable lands by local populations, causes a serious dysfunction in the soil's biological functioning (mineral deficiency, salt stress, etc.). This dysfunction, worsened by the climatic conditions (drought), requires the implementation of ecological engineering strategies allowing the rehabilitation of degraded areas through the restoration of essential ecological services. The first symptoms of weathering processes of soil quality in tropical and Mediterranean environments result in an alteration of the plant cover structure with, in particular, the pauperization of plant species diversity and abundance. This degradation is accompanied by a weakening of soils and an increase of the impact of erosion on the surface layer resulting in reduced fertility of soils in terms of their physicochemical characteristics as well as their biological ones (e.g., soil microbes). Among the microbial components particularly sensitive to erosion, symbiotic microorganisms (rhizobia, Frankia, mycorrhizal fungi) are known to be key components in the main terrestrial biogeochemical cycles (C, N and P). Many studies have shown the importance of the management of these symbiotic microorganisms in rehabilitation and revegetation strategies of degraded environments, but also in improving the productivity of agrosystems. In particular, the selection of symbionts and their inoculation into the soil were strongly encouraged in recent decades. These inoculants were selected not only for their impact on the plant, but also for their ability to persist in the soil at the expense of the residual native microflora. The performance of this technique was thus evaluated on the plant cover, but its impact on soil microbial characteristics was totally ignored. The role of microbial diversity on productivity and stability (resistance, resilience, etc.) of eco- and agrosystems has been identified relatively recently and has led to a questioning of the conceptual bases of controlled inoculation in sustainable land management. It has been suggested that the environmental characteristics of the area to rehabilitate should be taken into account, and more particularly its degradation level in relation to the threshold of ecological resilience. This consideration should lead to the optimization of the cultural practices to either (i) restore the original properties of an ecosystem in case of slightly degraded environments or (ii) transform an ecosystem in case of highly degraded soils (e.g., mine soils). In this chapter, we discuss, through various examples of experiments conducted in tropical and Mediterranean areas, the performance of different strategies to manage the microbial potential in soils (inoculation of exotic vs. native species, inoculation or controlled management potential microbial stratum via aboveground vegetation, etc.) based on the level of environmental degradation.     

Identification of susceptibility modules for coronary artery disease using a genome wide integrated network analysis

Although recent genome-wide association studies (GWAS) have identified a handful of variants with best significance for coronary artery disease (CAD), it remains a challenge to summarize the underlying biological information from the abundant genotyping data. Here, we propose an integrated network analysis that effectively combines GWAS genotyping dataset, protein–protein interaction (PPI) database, literature and pathway annotation information. This three-step approach was illustrated for a comprehensive network analysis of CAD as the following. First, a network was constructed from PPI database and CAD seed genes mined from the available literatures. Then, susceptibility network modules were captured from the results of gene-based association tests. Finally, susceptibility modules were annotated with potential mechanisms for CAD via the KEGG pathway database. Our network analysis identified four susceptibility modules for CAD including a complex module that consisted of 15 functional inter-connected sub-modules, AGPAT3–AGPAT4–PPAP2B module, ITGA11–ITGB1 module and EMCN–SELL module. MAPK10 and COL4A2 among the top-scored focal adhesion pathway related module were the most significant genes (MAPK10: OR = 32.5, P = 3.5 × 10^− 11; COL4A2: OR = 2.7, P = 2.8 × 10^− 10). The significance of the two genes were further validated by other two gene-based association tests (MAPK10: P = 0.009 and 0.007; COL4A2: P = 0.001 and 0.023) and another independent GWAS dataset (MAPK10: P = 0.001; COL4A2: P = 0.0004). Furthermore, 34 out of 44 previously reported CAD susceptibility genes were captured by our CAD PPI network and 17 of them were also significant genes. The susceptibility modules identified in our study might provide novel clues for the clarification of CAD pathogenesis in the future.     

Non-Chemical biofouling control in heat exchangers and seawater piping systems using acoustic pulses generated by an electrical discharge

Acoustic pulses generated by an electrical discharge (pulsed acoustics) were investigated as a means for biofouling control in two test formats, viz. a 5/8" outside diameter titanium tube and a mockup heat exchanger. The pulsed acoustic device, when operated at 17 kV, demonstrated 95% inhibition of microfouling over a 20 ft length of titanium tube over a 4-week period, comparable to chlorination in combination with a high-velocity flush. The pulsed acoustic device inhibited microfouling over a downstream distance of 15 ft, therefore, a single pulsed acoustic device is theoretically capable of protecting at least 30 ft of tube from microfouling (15 ft on either side of the device). A correlation between acoustic intensity in the frequency range 0.01-1 MHz and the level of biofouling inhibition was observed. The threshold acoustic intensity for microfouling inhibition was determined for this frequency range. It was also observed that the orientation of the device is critical to obtaining microfouling inhibition.     

支气管哮喘患者疾病认知状况调查及控制水平的影响因素分析

目的:调查支气管哮喘患者疾病认知状况,并分析控制水平的影响因素。方法:选取2018年7月~2020年7月期间贵州医科大学附属医院诊治的支气管哮喘患者100例,采用面对面问卷调查的方式调查所有患者疾病认知状况。采用哮喘控制测试(ACT)对患者哮喘控制水平进行评估。根据ACT结果将患者分为哮喘未控制组(n=57)和哮喘控制组(n=43)。分析哮喘控制水平的影响因素。结果:支气管哮喘患者对疾病认知相关问题的回答正确率均在60%以上,但仅有12%的患者使用过峰流速仪。本研究中100例患者均完成ACT,其中完全控制17例,控制良好26例,未控制57例,分别占比17.00%、26.00%、57.00%,哮喘控制率为43.00%。由单因素分析显示,支气管哮喘患者的哮喘控制水平与性别、家庭月收入、文化程度、家族史、吸烟史、居住处是否空气污染、病程、哮喘用药依从性、使用吸入性糖皮质激素治疗、抑郁情况、焦虑情况有关(P<0.05)。多因素Logistic回归分析显示:焦虑情况、抑郁情况、居住处空气污染、吸烟史是支气管哮喘患者哮喘控制水平的危险因素,而哮喘用药依从性、使用吸入性糖皮质激素治疗是支气管哮喘患者哮喘控制水平的保护因素(P<0.05)。结论:支气管哮喘患者对疾病有一定的正确认知,但仍未达到理想状态。哮喘控制水平受多种因素影响,可根据相关影响因素做出针对性的干预措施,以改善支气管哮喘控制水平。     

A potent antibacterial activity of new short d-enantiomeric lipopeptide against multi drug resistant bacteria

The emergence of drug-resistant pathogenic bacteria threatens human health. Resistance to existing antibiotics is increasing, while the emergence of new antibiotics is slowing. Cationic antimicrobial peptides (CAMPs) are fascinating alternative antibiotics because they possess a broad spectrum of activity, being active against both Gram-positive and Gram-negative bacteria including those resistant to traditional antibiotics. However, low bioavailability resulting from enzymatic degradation and attenuation by divalent cations like Mg²⁺ and Ca²⁺ limits their use as antibiotic agents. Here, we report the design of new CAMPs showing both high antibacterial activity and serum stability under physiological ion concentrations. The peptides were designed by applying two approaches, the use of d-enantiomer and lipidation. Based on the sequence of the CopW (LLWIALRKK-NH₂), a nonapeptide derived from coprisin, a series of novel d-form CopW lipopeptides with different acyl chain lengths (C6, C8, C10, C12, C14, and C16) were synthesized and evaluated with respect to their activity and salt sensitivity. Among the analogs, the d-form lipopeptide dCopW3 exhibited MIC values ranging from 1.25 to 5?μM against multidrug-resistant bacteria. Significantly, this compound did not induce bacterial resistance and was highly stable in human serum proteases. The results emphasize the potential of cationic d-form lipopeptide as therapeutically valuable antibiotics for treating drug-resistant bacterial infections.     

Robustness and aging—A systems-level perspective

The theory of robustness describes a system level property of evolutionary systems, which predicts tradeoffs of great interest for the systems biology of aging, such as accumulation of non-heritable damage, occurrence of fragilities and limitations in performance, optimized allocation of restricted resources and confined redundancies. According to the robustness paradigm cells and organisms evolved into a state of highly optimized tolerance (HOT), which provides robustness to common perturbations, but causes tradeoffs generally characterized as “robust yet fragile”. This raises the question whether the ultimate cause of aging is more than a lack of adaptation, but an inherent fragility of complex evolutionary systems. Since robustness connects to evolutionary designs, consideration of this theory provides a deeper connection between evolutionary aspects of aging, mathematical models and experimental data. In this review several mechanisms influential for aging are re-evaluated in support of robustness tradeoffs. This includes asymmetric cell division improving performance and specialization with limited capacities to prevent and repair age-related damage, as well as feedback control mechanisms optimized to respond to acute stressors, but unable to halt nor revert aging. Improvement in robustness by increasing efficiencies through cellular redundancies in larger organisms alleviates some of the damaging effects of cellular specialization, which can be expressed in allometric relationships. The introduction of the robustness paradigm offers unique insights for aging research and provides novel opportunities for systems biology endeavors.     

Nuclear BAG6-UBL4A-GET4 Complex Mediates DNA Damage Signaling and Cell Death

BCL2-associated athanogene 6 (BAG6) is a member of the BAG protein family, which is implicated in diverse cellular processes including apoptosis, co-chaperone, and DNA damage response (DDR). Recently, it has been shown that BAG6 forms a stable complex with UBL4A and GET4 and functions in membrane protein targeting and protein quality control. The BAG6 sequence contains a canonical nuclear localization signal and is localized predominantly in the nucleus. However, GET4 and UBL4A are found mainly in cytoplasm. Whether GET4 and UBL4A are also involved in DDR in the context of the BAG6 complex remains unknown. Here, we provide evidence that nuclear BAG6-UBL4A-GET4 complex mediates DDR signaling and damage-induced cell death. BAG6 appears to be the central component for the process, as depletion of BAG6 leads to the loss of both UBL4A and GET4 proteins and resistance to cell killing by DNA-damaging agents. In addition, nuclear localization of BAG6 and phosphorylation of BAG6 by ATM/ATR are also required for cell killing. UBL4A and GET4 translocate to the nucleus upon DNA damage and appear to play redundant roles in cell killing, as depletion of either one has no effect but co-depletion leads to resistance. All three components of the BAG6 complex are required for optimal DDR signaling, as BAG6, and to a lesser extent, GET4 and UBL4A, regulate the recruitment of BRCA1 to sites of DNA damage. Together our results suggest that the nuclear BAG6 complex is an effector in DNA damage response pathway and its phosphorylation and nuclear localization are important determinants for its function.     

Essential Role for the Mnk Pathway in the Inhibitory Effects of Type I Interferons on Myeloproliferative Neoplasm (MPN) Precursors

The mechanisms of generation of the antineoplastic effects of interferons (IFNs) in malignant hematopoietic cells remain to be precisely defined. We examined the activation of type I IFN-dependent signaling pathways in malignant cells transformed by Jak2V617F, a critical pathogenic mutation in myeloproliferative neoplasms (MPNs). Our studies demonstrate that during engagement of the type I IFN receptor (IFNAR), there is activation of Jak-Stat pathways and also engagement of Mnk kinases. Activation of Mnk kinases is regulated by the Mek/Erk pathway and is required for the generation of IFN-induced growth inhibitory responses, but Mnk kinase activation does not modulate IFN-regulated Jak-Stat signals. We demonstrate that for type I IFNs to exert suppressive effects in malignant hematopoietic progenitors from patients with polycythemia vera, induction of Mnk kinase activity is required, as evidenced by studies involving pharmacological inhibition of Mnk or siRNA-mediated Mnk knockdown. Altogether, these findings provide evidence for key and essential roles of the Mnk kinase pathway in the generation of the antineoplastic effects of type I IFNs in Jak2V617F-dependent MPNs.