Depletion of the heaviest stable N isotope is associated with NH4 +/NH3 toxicity in NH4 +-fed plants

Background: In plants, nitrate (NO(3)(-)) nutrition gives rise to a natural N isotopic signature (delta(15)N), which correlates with the delta(15)N of the N source. However, little is known about the relationship between the delta(15)N of the N source and the (14)N/(15)N fractionation in plants under ammonium (NH(4)(+)) nutrition. When NH(4)(+) is the major N source, the two forms, NH(4)(+) and NH(3), are present in the nutrient solution. There is a 1.025 thermodynamic isotope effect between NH(3) (g) and NH(4)(+)(aq) which drives to a different delta(15)N. Nine plant species with different NH(4)(+)-sensitivities were cultured hydroponically with NO(3)(-) or NH(4)(+) as the sole N sources, and plant growth and delta(15)N were determined. Short-term NH(4)(+)/NH(3) uptake experiments at pH 6.0 and 9.0 (which favours NH(3) form) were carried out in order to support and substantiate our hypothesis. N source fractionation throughout the whole plant was interpreted on the basis of the relative transport of NH(4)(+) and NH(3). -- Results: Several NO(3)(-)-fed plants were consistently enriched in (15)N, whereas plants under NH(4)(+) nutrition were depleted of (15)N. It was shown that more sensitive plants to NH(4)(+) toxicity were the most depleted in (15)N. In parallel, N-deficient pea and spinach plants fed with (15)NH(4)(+) showed an increased level of NH(3) uptake at alkaline pH that was related to the (15)N depletion of the plant. Tolerant to NH(4)(+) pea plants or sensitive spinach plants showed similar trend on (15)N depletion while slight differences in the time kinetics were observed during the initial stages. The use of RbNO(3) as control discarded that the differences observed arise from pH detrimental effects. -- Conclusions: This article proposes that the negative values of delta(15)N in NH(4)(+)-fed plants are originated from NH(3) uptake by plants. Moreover, this depletion of the heavier N isotope is proportional to the NH(4)(+)/NH(3) toxicity in plants species. Therefore, we hypothesise that the low affinity transport system for NH(4)(+) may have two components: one that transports N in the molecular form and is associated with fractionation and another that transports N in the ionic form and is not associated with fractionation.

Brca1 is expressed in human microglia and is dysregulated in human and animal model of ALS

Background: There is growing evidence that microglia are key players in the pathological process of amyotrophic lateral sclerosis (ALS). It is suggested that microglia have a dual role in motoneurone degeneration through the release of both neuroprotective and neurotoxic factors. Results: To identify candidate genes that may be involved in ALS pathology we have analysed at early symptomatic age (P90), the molecular signature of microglia from the lumbar region of the spinal cord of hSOD1(G93A) mice, the most widely used animal model of ALS. We first identified unique hSOD1(G93A) microglia transcriptomic profile that, in addition to more classical processes such as chemotaxis and immune response, pointed toward the potential involvement of the tumour suppressor gene breast cancer susceptibility gene 1 (Brca1). Secondly, comparison with our previous data on hSOD1(G93A) motoneurone gene profile substantiated the putative contribution of Brca1 in ALS. Finally, we established that Brca1 protein is specifically expressed in human spinal microglia and is up-regulated in ALS patients. Conclusions: Overall, our data provide new insights into the pathogenic concept of a non-cell-autonomous disease and the involvement of microglia in ALS. Importantly, the identification of Brca1 as a novel microglial marker and as possible contributor in both human and animal model of ALS may represent a valid therapeutic target. Moreover, our data points toward novel research strategies such as investigating the role of oncogenic proteins in neurodegenerative diseases.