One for All and All for One! Increased Plant Heavy Metal Tolerance by Growth-Promoting Microbes: A Metabolomics Standpoint

Increasing urbanization and industrialization cause the unavoidable mass release of pollutants in the environment. Nanoparticles and heavy metals are among the most threatening agents affecting ecosystems. Agriculture is severely affected by these eco-toxicants: crop productivity dramatically drops, since plant growth and development are negatively impacted. Arable lands are sinks accumulating pollutants which establish physic-chemical associations with soil particles: this leads to changes in the properties of soils, namely texture and, ultimately, alters the availability of nutrients. Green technologies in agriculture rely on the use of environmental-friendly alternatives to boost crop productivity under exogenous constraints. In this context, the use of beneficial plant growth-promoting microbes (PGPMs) is seen as a promising strategy to protect plants against the stress triggered by eco-toxicants. A strong body of evidence in the literature has shown that some PGPMs (e.g. local strains) are natural heavy metal accumulators and may also influence the metabolome of the plants they associate with. Therefore, their action is both direct and indirect. An example of the former is the secretion of extracellular polysaccharides (EPS) which function as a mechanical barrier and entrap heavy metals; an indirect effect is the priming of defence responses leading to the synthesis of specific classes of plant secondary metabolites. In this chapter, the accent will be put on the analytical power of metabolomics in conjunction with meta-metabolomics (i.e. the analysis of the metabolome of an entire community of microbes associating with different plant organs). The ultimate goal is to unravel the mechanisms responsible for the increased heavy metal tolerance in crops establishing an interaction with PGPMs. We will end our survey with some perspectives on innovative strategies in agrobiotechnology valorising PGPMs in conjunction with fertilization using beneficial elements like silicon (Si) and capable of providing sustainable solutions facing the ever-increasing release of pollutants in the environment

Natalizumab plus interferon beta-1a reduces lesion formation in relapsing multiple sclerosis

The SENTINEL study showed that the addition of natalizumab improved outcomes for patients with relapsing multiple sclerosis (MS)who had experienced disease activitywhile receiving interferon beta-1a (IFNβ-1a) alone. Previously unreported secondary and tertiary magnetic resonance imaging (MRI) measures are presented here. Patients received natalizumab 300 mg (n=589) or placebo (n=582) intravenously every 4 weeks plus IFNβ-1a 30 μg intramuscularly once weekly. Annual MRI scans allowed comparison of a range of MRI end points versus baseline. Over 2 years, 67% of patients receiving natalizumab plus IFNβ-1a remained free of newor enlarging T2- lesions compared with 30% of patients receiving IFNβ-1a alone. The mean change from baseline in T2 lesion volume over 2 years decreased in patients receiving natalizumab plus IFNβ-1a and increased in those receiving IFNβ-1a alone (–277.5 mm3 versus 525.6 mm3; pb0.001). Compared with IFNβ-1a alone, add-on natalizumab therapy resulted in a smaller increase in mean T1-hypointense lesion volume after 2 years (1821.3 mm3 versus 2210.5mm3; pb0.001), a smaller mean number of new T1-hypointense lesions over 2 years (2.3 versus 4.1; pb0.001), and a slower rate of brain atrophy during the second year of therapy (–0.31% versus –0.40%; p=0.020). Natalizumab add-on therapy reduced gadolinium-enhancing, T1-hypointense, and T2 MRI lesion activity and slowed brain atrophy progression in patients with relapsing MS who experienced disease activity despite treatment with IFNβ-1a alon

Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.

Item does not contain fulltextBACKGROUND: Interferon beta is used to modify the course of relapsing multiple sclerosis. Despite interferon beta therapy, many patients have relapses. Natalizumab, an alpha4 integrin antagonist, appeared to be safe and effective alone and when added to interferon beta-1a in preliminary studies. METHODS: We randomly assigned 1171 patients who, despite interferon beta-1a therapy, had had at least one relapse during the 12-month period before randomization to receive continued interferon beta-1a in combination with 300 mg of natalizumab (589 patients) or placebo (582 patients) intravenously every 4 weeks for up to 116 weeks. The primary end points were the rate of clinical relapse at 1 year and the cumulative probability of disability progression sustained for 12 weeks, as measured by the Expanded Disability Status Scale, at 2 years. RESULTS: Combination therapy resulted in a 24 percent reduction in the relative risk of sustained disability progression (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P=0.02). Kaplan-Meier estimates of the cumulative probability of progression at two years were 23 percent with combination therapy and 29 percent with interferon beta-1a alone. Combination therapy was associated with a lower annualized rate of relapse over a two-year period than was interferon beta-1a alone (0.34 vs. 0.75, P<0.001) and with fewer new or enlarging lesions on T(2)-weighted magnetic resonance imaging (0.9 vs. 5.4, P<0.001). Adverse events associated with combination therapy were anxiety, pharyngitis, sinus congestion, and peripheral edema. Two cases of progressive multifocal leukoencephalopathy, one of which was fatal, were diagnosed in natalizumab-treated patients. CONCLUSIONS: Natalizumab added to interferon beta-1a was significantly more effective than interferon beta-1a alone in patients with relapsing multiple sclerosis. Additional research is needed to elucidate the benefits and risks of this combination treatment. (ClinicalTrials.gov number, NCT00030966.)