Sodium phenylbutyrate controls neuroinflammatory and antioxidant activities and protects dopaminergic neurons in mouse models of Parkinson's disease

Neuroinflammation and oxidative stress underlie the pathogenesis of various neurodegenerative disorders. Here we demonstrate that sodium phenylbutyrate (NaPB), an FDA-approved therapy for reducing plasma ammonia and glutamine in urea cycle disorders, can suppress both proinflammatory molecules and reactive oxygen species (ROS) in activated glial cells. Interestingly, NaPB also decreased the level of cholesterol but involved only intermediates, not the end product of cholesterol biosynthesis pathway for these functions. While inhibitors of both geranylgeranyl transferase (GGTI) and farnesyl transferase (FTI) inhibited the activation of NF-κB, inhibitor of GGTI, but not FTI, suppressed the production of ROS. Accordingly, a dominant-negative mutant of p21(rac), but not p21(ras), attenuated the production of ROS from activated microglia. Inhibition of both p21(ras) and p21(rac) activation by NaPB in microglial cells suggests that NaPB exerts anti-inflammatory and antioxidative effects via inhibition of these small G proteins. Consistently, we found activation of both p21(ras) and p21(rac)in vivo in the substantia nigra of acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Oral administration of NaPB reduced nigral activation of p21(ras) and p21(rac), protected nigral reduced glutathione, attenuated nigral activation of NF-κB, inhibited nigral expression of proinflammatory molecules, and suppressed nigral activation of glial cells. These findings paralleled dopaminergic neuronal protection, normalized striatal neurotransmitters, and improved motor functions in MPTP-intoxicated mice. Consistently, FTI and GGTI also protected nigrostriata in MPTP-intoxicated mice. Furthermore, NaPB also halted the disease progression in a chronic MPTP mouse model. These results identify novel mode of action of NaPB and suggest that NaPB may be of therapeutic benefit for neurodegenerative disorders.     

A comparison of the strength of biodiversity effects across multiple functions

In order to predict which ecosystem functions are most at risk from biodiversity loss, meta-analyses have generalised results from biodiversity experiments over different sites and ecosystem types. In contrast, comparing the strength of biodiversity effects across a large number of ecosystem processes measured in a single experiment permits more direct comparisons. Here, we present an analysis of 418 separate measures of 38 ecosystem processes. Overall, 45 % of processes were significantly affected by plant species richness, suggesting that, while diversity affects a large number of processes not all respond to biodiversity. We therefore compared the strength of plant diversity effects between different categories of ecosystem processes, grouping processes according to the year of measurement, their biogeochemical cycle, trophic level and compartment (above- or belowground) and according to whether they were measures of biodiversity or other ecosystem processes, biotic or abiotic and static or dynamic. Overall, and for several individual processes, we found that biodiversity effects became stronger over time. Measures of the carbon cycle were also affected more strongly by plant species richness than were the measures associated with the nitrogen cycle. Further, we found greater plant species richness effects on measures of biodiversity than on other processes. The differential effects of plant diversity on the various types of ecosystem processes indicate that future research and political effort should shift from a general debate about whether biodiversity loss impairs ecosystem functions to focussing on the specific functions of interest and ways to preserve them individually or in combination.     

Hydrologic flowpaths influence inorganic and organic nutrient leaching in a forest soil

Hydrologic pathways through soil affect element leaching by determining the relative importance of biogeochemical processes such as sorption and decomposition. We used stable hydrogen isotopes of water (δD) to examine the influence of flowpaths on soil solution chemistry in a mature spruce–hemlock forest in coastal Oregon, USA. Soil solutions (50 cm depth, n = 13) were collected monthly for 1 year and analyzed for δD, major ions and dissolved organic carbon (DOC) and nitrogen (DON). We propose that the variability of δD can be used as an index of flowpath length and contact time. Throughfall variability in δD was much greater than soil solution variability, illustrating that soil solution integrates the variation in inputs. Lysimeters with greater variation in δD presumably have a greater proportion of flow through rapid flowpaths such as macropores. The variation in soil solution δD for individual lysimeters explained up to 53% of the variation in soil solution chemistry, and suggests that flowpaths influence leaching of some constituents. Soil solutions from lysimeters with greater δD variation had higher DOC and DON (r ² = 0.51 and 0.37, respectively), perhaps because transport via macropores reduces interaction of DOM with the soil matrix. In contrast, nitrate concentrations were highest in lysimeters with a small variation in δD, where long contact time and low DOC concentrations may yield higher net nitrification. Our results demonstrate the utility of stable isotopes to link flowpaths and soil solution chemistry, and illustrate how the spatial complexity of soils can influence ecosystem-level nutrient losses.     

Glutamate decarboxylase activity in Trichoderma viride conidia and developing mycelia

Glutamic acid decarboxylase (GAD) activity was measured in homogenates of conidia and both submerged and aerial mycelia of Trichoderma viride. The GAD activity in conidia had a temperature optimum at 30 degrees C and a pH optimum at pH 4. GAD was stimulated by EDTA (2 mM) and was insensitive to treatment with calmodulin antagonists calmidazolium (10 microM) or phenothiazine neuroleptics (60 microM). Cyclosporin A (up to 300 microM) partially inhibited GAD in the homogenate, but not in the supernatant obtained after centrifuging the homogenate. Attempts to release GAD activity from the homogenate using high ionic strength, detergents, or urea failed. Freezing-thawing led to the partial increase of activity in the conidial homogenate. These results indicate that GAD is a membrane-bound enzyme. The highest specific activity of GAD was present in the mitochondrial/vacuolar organellar fraction. Germination of conidia in the submerged culture led to a temporary decrease in GAD activity. After prolonged cultivation, the activity displayed quasi-oscillatory changes. The stationary state was characterized by a high GAD activity. The presence of gamma-aminobutyric acid in the submerged mycelia was demonstrated. In surface culture in the dark, GAD activity increased in a monophasic manner until conidia formation. The illumination of dark-cultivated mycelia by a white-light pulse caused a dramatic increase in GAD activity. Light-induced changes were not observed in mutants with delayed onset of conidiation. In the dark or upon illumination by light pulse, the increase of GAD activity preceded the appearance of conidia. Thus, GAD activity in T. viride is closely associated with its developmental status and may represent a link between differentiation events and energy metabolism.     

Mycorrhiza influences plant community structure in succession on spoil banks

The experiment simulated a plant succession stage when perennial grasses (e.g. Calamagrostis epigejos) invade communities of annuals with different mycotrophy (e.g. Atriplex sagittata and Tripleurospermum inodorum) on coalmine spoil banks. Communities of these three model species were planted in 30 l microcosms either in the presence of pre-established mycelium network of three arbuscular mycorrhizal fungi (AMF) species (individually and in a mixture) or without AMF. Different AMF species had significantly different effects on individual plant species’ growth, which resulted in changes in plant community structure. While in the no-AMF treatment the non-mycotrophic plant species A. sagittata contributed nearly 70% to the total plant biomass, in the presence of the 3 AMF mixture the contribution of this species was only about 10%. Different effects of AMF on tiller formation by C. epigejos suggest that some AMF could have greater potential to promote the replacement of annuals by perennial grasses than others. It can be concluded that not merely the presence but also the identity of AMF present on spoil banks can affect the coexistence of plant dominants, the community structure and the progress of plant succession.     

Cell division and sister chromatid exchanges in 45,X/46,X,i(Xq) mosaicism

Summary The kinetics of cell division and sister chromatid exchanges were studied in PHA-stimulated short-term cultivations of peripheral blood by means of the BUDR/FPG technique in controls and in five patients with 45,X/46,X,i(Xq) mosaicism. No significant differences in the length of the cell cycle were observed between 45,X/46,X,i(Xq) and control 46,XX cells. The number of SCE on late i(Xq) was only nonsignificantly elevated (0.6 per i(Xq)) against the value expected on the basis of its relative length.     

European Roe Deer Increase Vigilance When Faced with Immediate Predation Risk by Eurasian Lynx

Prey animals must balance antipredatory behaviour with foraging behaviour. According to the risk allocation hypothesis, prey increase antipredatory behaviour and reduce foraging activity during pulses of high risk, but with continuous risk, other activities must continue and antipredatory behaviour decreases despite the risk. We studied the impact of lynx presence on the vigilance behaviour of wild roe deer under conditions of (i) a pulsed elevated risk by experimentally spreading lynx urine as an olfactory cue, and (ii) continuous risk by comparing an area where lynx was eradicated 160 years ago to an area where lynx has been re‐introduced 30 years ago. Roe deer were extremely vigilant in response to the predator olfactory cue; however, roe deer vigilance did not differ measurably among areas with or without potential lynx presence. Deer were more vigilant before sunset than during the night at both study areas, probably due to long‐term adaptation of roe deer to human hunting during daytime. Vigilance decreased from August to September even though activity of lynx increases in autumn, which may be a result either of increased foraging due to decrease in food quality in autumn, or of changes in social organization of the deer. Our results suggested that the degree of vigilance depends on environmental cues. We found that roe deer respond to lynx urine despite a long absence of lynx in the ecosystem. Our results support the risk allocation hypothesis for responses to pulses of high risk but not for responses to continuous elevated levels of risk.