Systemic perturbations of the kynurenine pathway precede progression to dementia independently of amyloid-β

Increasing evidence suggests that kynurenine pathway (KP) dyshomeostasis may promote disease progression in dementia. Studies in Alzheimer's disease (AD) patients confirm KP dyshomeostasis in plasma and cerebrospinal fluid (CSF) which correlates with amyloid-β and tau pathology. Herein, we performed the first comprehensive study assessing baseline levels of KP metabolites in participants enrolling in the Australian Imaging Biomarkers Flagship Study of Aging. Our purpose was to test the hypothesis that changes in KP metabolites may be biomarkers of dementia processes that are largely silent. We used a cross-sectional analytical approach to assess non-progressors (N = 73); cognitively normal (CN) or mild cognitive impairment (MCI) participants at baseline and throughout the study, and progressors (N = 166); CN or MCI at baseline but progressing to either MCI or AD during the study. Significant KP changes in progressors included increased 3-hydroxyanthranilic acid (3-HAA) and 3-hydroxyanthranilic acid/anthranilic acid (3-HAA/AA) ratio, the latter having the largest effect on the odds of an individual being a progressor (OR 35.3; 95% CI between 14 and 104). 3-HAA levels were hence surprisingly bi-phasic, high in progressors but low in non-progressors or participants who had already transitioned to MCI or dementia. This is a new, unexpected and interesting result, as most studies of the KP in neurodegenerative disease show reduced 3-HAA/AA ratio after diagnosis. The neuroprotective metabolite picolinic acid was also significantly decreased while the neurotoxic metabolite 3-hydroxykynurenine increased in progressors. These results were significant even after adjustment for confounders. Considering the magnitude of the OR to predict change in cognition, it is important that these findings are replicated in other populations. Independent validation of our findings may confirm the utility of 3-HAA/AA ratio to predict change in cognition leading to dementia in clinical settings

Surface-wave imaging of the weakly-extended Malawi Rift from ambient-noise and teleseismic Rayleigh waves from onshore and lake-bottom seismometers

Located at the southernmost sector of the Western Branch of the East African Rift System, the Malawi Rift exemplifies an active, magma-poor, weakly extended continental rift. To investigate the controls on rifting, we image crustal and uppermost mantle structure beneath the region using ambient-noise and teleseismic Rayleigh-wave phase velocities between 9 and 100 s period. Our study includes six lake-bottom seismometers located in Lake Malawi (Nyasa), the first time seismometers have been deployed in any of the African rift lakes. Noise-levels in the lake are lower than that of shallow oceanic environments and allow successful application of compliance corrections and instrument orientation determination. Resulting phase-velocity maps reveal slow velocities primarily confined to Lake Malawi at short periods (T 25 s) a prominent low-velocity anomaly exists beneath the Rungwe Volcanic Province at the northern terminus of the rift basin. Estimates of phase-velocity sensitivity indicates these low velocities occur within the lithospheric mantle and potentially uppermost asthenosphere, suggesting that mantle processes may control the association of volcanic centers and the localization of magmatism. Beneath the main portion of the Malawi Rift, a modest reduction in velocity is also observed at periods sensitive to the crust and upper mantle, but these velocities are much higher than those observed beneath Rungwe

Pulsar polarisation below 200 MHz: Average profiles and propagation effects

Aims: We present the highest-quality polarisation profiles to date of 16 non-recycled pulsars and four millisecond pulsars, observed below 200 MHz with the LOFAR high-band antennas. Based on the observed profiles, we perform an initial investigation of expected observational effects resulting from the propagation of polarised emission in the pulsar magnetosphere and the interstellar medium. Methods: The polarisation data presented in this paper have been calibrated for the geometric-projection and beam-shape effects that distort the polarised information as detected with the LOFAR antennas. We have used RM Synthesis to determine the amount of Faraday rotation in the data at the time of the observations. The ionospheric contribution to the measured Faraday rotation was estimated using a model of the ionosphere. To study the propagation effects, we have compared our low-frequency polarisation observations with archival data at 240, 400, 600, and 1400 MHz. Results: The predictions of magnetospheric birefringence in pulsars have been tested using spectra of the pulse width and fractional polarisation from multifrequency data. The derived spectra offer only partial support for the expected effects of birefringence on the polarisation properties, with only about half of our sample being consistent with the model's predictions. It is noted that for some pulsars these measurements are contaminated by the effects of interstellar scattering. For a number of pulsars in our sample, we have observed significant variations in the amount of Faraday rotation as a function of pulse phase, which is possibly an artefact of scattering. These variations are typically two orders of magnitude smaller than that observed at 1400 MHz by Noutsos et al. (2009), for a different sample of southern pulsars. In this paper we present a possible explanation for the difference in magnitude of this effect between the two frequencies, based on scattering. Finally, we have estimated the magnetospheric emission heights of low-frequency radiation from four pulsars, based on the phase lags between the flux-density and the PA profiles, and the theoretical framework of Blaskiewicz et al. (1991, ApJ, 370, 643). These estimates yielded heights of a few hundred km; at least for PSR B1133+16, this is consistent with emission heights derived based on radius-to-frequency mapping, but is up to a few times larger than the recent upper limit based on pulsar timing. Conclusions: Our work has shown that models, like magnetospheric birefringence, cannot be the sole explanation for the complex polarisation behaviour of pulsars. On the other hand, we have reinforced the claim that interstellar scattering can introduce a rotation of the PA with frequency that is indistinguishable from Faraday rotation and also varies as a function of pulse phase. In one case, the derived emission heights appear to be consistent with the predictions of radius-to-frequency mapping at 150 MHz, although this interpretation is subject to a number of systematic uncertainties

Effects of host plant drought stress on the performance of the bird cherry-oat aphid, Rhopalosiphum padi (L.): a mechanistic analysis

1. The growth (increase in height and leaf number) of four grass species was reduced by a -0.5 MPa drought stress, but the performance of an associated herbivore, Rhopalosiphum padi (L.), was not affected consistently. The intrinsic rate of increase of R. padi was reduced by drought stress on three grass species, including Dactylis glomerata (L.), but was unaffected on Arrhenatherum elatius (L.). Therefore, there is no general relationship in the effect of plant drought on an insect herbivore, even among closely related host plant species. 2. Drought stress increased the quality of plant phloem sap, as indicated by increased sieve element osmotic pressure and essential amino acid concentrations. Thus, diet quality could not account for the reduced performance of R. padi under drought stress. The concentration of essential amino acids in the phloem of well-watered A. elatius was, however, lower than that of well-watered D. glomerata, correlating with the decreased performance of aphids on well-watered A. elatius. 3. There were no differences in aphid feeding duration between watering treatments or plant species but sap ingestion rates were reduced significantly under drought stress. 4. Using the measure of dietary amino acid concentrations and the estimate of sap ingestion, the essential amino acid flux through aphids was calculated. Compared with the flux through aphids feeding on well-watered D. glomerata, there was a reduction in aphids feeding on drought-stressed D. glomerata and drought-stressed A. elatius due to lower sap ingestion rates. The flux through aphids on well-watered A. elatius was also reduced due to low phloem essential amino acid concentrations. Thus, the performance of an aphid is correlated with the availability and accessibility of essential amino acids

Retargeting of coronavirus by substitution of the spike glycoprotein ectodomain: crossing the host cell species barrier

Coronaviruses generally have a narrow host range, infecting one or just a few species. Using targeted RNA recombination, we constructed a mutant of the coronavirus mouse hepatitis virus (MHV) in which the ectodomain of the spike glycoprotein (S) was replaced with the highly divergent ectodomain of the S protein of feline infectious peritonitis virus. The resulting chimeric virus, designated fMHV, acquired the ability to infect feline cells and simultaneously lost the ability to infect murine cells in tissue culture. This reciprocal switch of species specificity strongly supports the notion that coronavirus host cell range is determined primarily at the level of interactions between the S protein and the virus receptor. The isolation of fMHV allowed the localization of the region responsible for S protein incorporation into virions to the carboxy-terminal 64 of the 1,324 residues of this protein. This establishes a basis for further definition of elements involved in virion assembly. In addition, fMHV is potentially the ideal recipient virus for carrying out reverse genetics of MHV by targeted RNA recombination, since it presents the possibility of selecting recombinants, no matter how defective, that have regained the ability to replicate in murine cells

The influence of below-ground herbivory and defoliation of a legume on nitrogen transfer to neighbouring plants

1. Both foliar and root herbivory can alter the exudation of carbon from plant roots, which in turn can affect nitrogen availability in the soil. However, few studies have investigated the effects of herbivory on N fluxes from roots, which can directly increase N availability in the soil and uptake by neighbouring plants. Moreover, the combined effects of foliar and root herbivory on N fluxes remains unexplored. 2. We subjected the legume white clover (Trifolium repens L.) to defoliation (through clipping) and root herbivory (by an obligate root-feeding nematode, Heterodera trifolii Goggart) to examine how these stresses individually, and simultaneously, affected the transfer of T. repens-derived N to neighbouring perennial ryegrass (Lolium perenne L.) plants using 15N stable-isotope techniques. We also examined the effects of defoliation and root herbivory on the size of the soil microbial community and the growth response of L. perenne. 3. Neither defoliation nor root herbivory negatively affected T. repens biomass. On the contrary, defoliation increased root biomass (34%) and total shoot production by T. repens (100%). Furthermore, defoliation resulted in a fivefold increase in T. repens-derived 15N recovered in L. perenne roots, and increased the size of the soil microbial biomass (77%). In contrast, root herbivory by H. trifolii slightly reduced 15N transfer from T. repens to L. perenne when T. repens root 15N concentration was included as a covariate, and root herbivory did not affect microbial biomass. Growth of L. perenne was not affected by any of the treatments. 4. Our findings demonstrate that defoliation of a common grassland legume can substantially increase the transfer of its N to neighbouring plants by directly affecting below-ground N fluxes. These finding require further examination under field conditions but, given the prevalence of N-limitation of plant productivity in terrestrial ecosystems, increased transfer of N from legumes to non-N-fixing species could alter competitive interactions, with implications for plant community structure

How does global change affect the strength of trophic interactions?

Recent research has generally shown that a small change in the number of species in a food web can have consequences both for community structure and ecosystem processes. However ‘change’ is not limited to just the number of species in a community, but might include an alteration to such properties as precipitation, nutrient cycling and temperature, all of which are correlated with productivity. Here we argue that predicted scenarios of global change will result in increased plant productivity. We model three scenarios of change using simple Lotka–Volterra dynamics, which explore how a global change in productivity might affect the strength of local species interactions and detail the consequences for community and ecosystem level stability. Our results indicate that (i) at local scales the average population size of consumers may decline because of poor quality food resources, (ii) that the strength of species interactions at equilibrium may become weaker because of reduced population size, and (iii) that species populations may become more variable and may take longer to recover from environmental or anthropogenic disturbances. At local scales interaction strengths encompass such properties as feeding rates and assimilation efficiencies, and encapsulate functionally important information with regard to ecosystem processes. Interaction strengths represent the pathways and transfer of energy through an ecosystem. We examine how such local patterns might be affected given various scenarios of ‘global change’ and discuss the consequences for community stability and ecosystem functioning. [KEYWORDS: Community; Ecosystems; Food webs; Herbivore; Plant; Predators; Prey; Stability]