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ROLE OF MUTANT VAPB IN THE PATHOGENESIS OF AMYOTROPHIC LATERAL SCLEROSIS: GAIN OR LOSS OF FUNCTION?
Full text linkAmyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by degeneration of motorneurons leading to progressive paralysis and eventually death due to respiratory failure. So far, no effective treatments are available for this devastating disease. Interestingly, genetic forms of ALS show the same pathological alterations observed in the most frequent sporadic cases. For this reason, studying the role of single disease causing mutations is important to gain insight into the pathophysiological events that lead to disease development.
Ten years ago a mutation in the gene encoding for VAPB was associated with a dominantly inherited form of ALS (termed ALS8). Moreover, sporadic ALS patients have reduced levels of the endogenous protein. VAPB belongs, along with its homologue VAPA, to the VAP protein family: ER resident tail anchored proteins that, thanks to their binding partners, are involved in several cellular functions like lipid transport, ER stress and membrane contact site formation. The ALS-associated mutation P56S dramatically alters VAPB structure, thus preventing the binding to its physiological interactors and causing its aggregation.
The cellular and molecular mechanisms underlying pathogenicity of mutant VAPB are still poorly understood. It is still unclear whether P56S-VAPB-generated inclusions exert a direct toxic function or whether reduced levels of the wt protein are sufficient to trigger the disease. An intermediate situation, where both mechanisms contribute to ALS development, could also be possible.
The aim of my thesis is to analyze the contribution of mutant VAPB gain or loss of function in the development of ALS. To reach this goal, I used two complementary approaches: I analyzed cellular models that either express moderate levels of P56S-VAPB or have reduced levels of the endogenous protein.
Our findings would be relevant not only to understand the pathogenesis of ALS8, but also for forms of sporadic ALS, in which VAPB levels are reduced
Effect of compost application rate on carbon degradation and retention in soils
Full text linkWe investigated the effect of a single compost application at two rates (50 and 85 Mg ha-1) on carbon (C) degradation and retention in an agricultural soil cropped with maize after 150 d. We used both C mass balance and soil respiration data to trace the fate of compost C. Our results indicated that compost C accumulated in the soil after 150 d was 4.24 Mg ha-1 and 6.82 Mg C ha-1 for 50 and 85 Mg ha-1 compost rate, respectively. Compost C was sequestered at the rate of 623 and 617 g C kg-1 compost TOC for 50 and 85 Mg ha-1 compost dose, respectively. These results point to a linear response between dose of application and both C degradation and retention. The amount of C sequestered was similar to the total recalcitrant C content of compost, which was 586 g C kg-1 compost TOC, indicating that, probably, during the short experiment, the labile C pool of compost (414 g C kg-1 of compost TOC) was completely degraded. Soil respiration measured at different times during the crop growth cycle was stable for soils amended with compost (CO2 flux of 0.96 ± 0.11 g CO2 m-2 h-1 and 1.07 ± 0.10 g CO2 m-2 h-1, respectively, for 50 and 85 Mg ha-1), whereas it increased in the control. The CO2 flux due to compost degradation only, though not statistically significant, was always greatest for the highest compost doses applied (0.22 ± 0.40 g CO2 m-2 h-1 and 0.33 ± 0.25 g CO2 m-2 h-1 for the 50 and 85 Mg ha-1 compost dose, respectively). This seems to confirm the highest C degradation for the 85 Mg ha-1 compost dose as a consequence of the presence of more labile C. Unlike other studies, the results show a slight increase in the fraction of carbon retained with the increase in compost application rate. This could be due to the highly stable state of the compost prior to application, although it could also be due to sampling uncertainty. Further investigations are needed to better explain how the compost application rate affects carbon sequestration, and how characterization into labile and recalcitrant C can predict the amount of C sequestered in the soil
Biochemical origin and refractory properties of humic acid extracted from the maize plant
No full textHumic acids (HA) contribute to soil fertility because of their chemical, physical, and biological properties. The origin of HAs in soils has puzzled scientists for decades, and what HAs are and what their origin is remain unclear. The isolation of HAs in plants, which have characteristics close to soil HAs, suggests the probable origin of soil-HA is the preservation of plant tissue, indicating biochemical origin. In this paper HA from maize plant at different stages of maturity is isolated, from which it was found that the evolution of this fraction depends on and is derived from cell wall formation. Evidence was also found that HA was above all composed of lignin and cutin residues, and was characterized by low surface area. After 8 months of incubation in both mineral-artificial and natural soils, humic acid isolated form maize plant could be recovered intact
The effect of commercial humic acid on tomato plants growth and mineral nutrition
No full textThe effects of humic acids extracted from two commercially-available products (CP-A prepared from peat and CP-B prepared from leonardite) on the growth and mineral nutrition of tomato plants (Lycopersicon esculentum L.) in hydroponics culture were tested at concentrations of 20 and 50 mg L-1. Both the humic acids tested stimulated plants growth. The CP-A stimulated only root growth, especially at 20 mg L-1 [23% and 22% increase over the control, on fresh weight basis (f.w.b.), and dry weight basis (d.w.b.), respectively]. In contrast, CP-B showed a positive effect on both shoots and roots, especially at 50 mg L-1 (shoots: 8% and 9% increase over the control; roots: 18% and 16% increase over the control, on f.w.b. and d.w.b., respectively). Total ion uptake by the plants was affected by the two products. In particular, CP-A showed an increase in the uptake of nitrogen (N), phosphorus (P), iron (Fe), and copper (Cu), whereas, CP-B showed positive effects for N, P, and Fe uptake. The change in the Fe content was the most appreciable effect on mineral nutrition (CP-A: 41% and 33% increase over the control for 20 mg L-1 and 50 mg L-1, respectively; CP-B: 31% and 46% increase over the control for 20 mg L-1 and 50 mg L-1, respectively). Increases in Fe concentration in the plant roots were especially pronounced (CP-A: 113% and 123% increases with respect to controls for the 20 mg L-1 and 50 mg L-1 treatments; CP-B: 135% and 161% increases with respect to the control for 20 mg L-1 and 50 mg L-1 treatments). On the basis of the current experiments and from evidence in the literature, reduction of Fe3+ to Fe2+ by humic acid is considered as a possibility to explain a higher Fe availability for the plants
Influenza delle vie biosintetiche della lignina in piante di mais “wild type” e brown midrib 3 (bm3) sulla formazione e conservazione nel suolo di molecole umo-simili
No full textCompost effect on soil humic acid : a NMR study
No full textThe humic acid (HA) fraction of a food and vegetable residues compost (CM) was taken as indicator to trace the fate of CM organic matter in four years CM amended soil. H-1 and C-13 NMR spectroscopy were used to investigate the nature of the HA isolates from CM, control Soil (S-4) and amended soil. The result indicated a significant structural difference between CM HA and S-4 HA, and supported the presence of both HA fractions in soil at the end of the amendment trials. However, the nature and content of CM HA in soil did not fully explain the increase of soil cation exchange capacity (CEC) after amendment. All CM humic fractions (i.e., fulvic acid, humic acid and humin) were found to contribute to the change of the soil organic matter composition. It is concluded that although CM HA is a suitable indicator of the survival of compost organic matter in soil during amendment, all three humic fractions should be monitored and analyzed to fully understand changes in the composition and properties of amended soil. (c) 2006 Elsevier Ltd. All rights reserved
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