Alzheimer’s disease-associated peptide Aβ₄₂ mobilizes ER Ca²⁺ via InsP₃R-dependent and -independent mechanisms

Dysregulation of Ca2+ homeostasis is considered to contribute to the toxic action of the Alzheimer’s Disease (AD) associated Amyloid β-peptide (Aβ). Ca2+ fluxes across the plasma membrane and release from intracellular stores have both been reported to underlie the Ca2+ fluxes induced by Aβ42. Here, we investigated the contribution of Ca2+ release from the endoplasmic reticulum (ER) to the effects of Aβ42 upon Ca2+ homeostasis and the mechanism by which Aβ42 elicited these effects. Consistent with previous reports, application of soluble oligomeric forms of Aβ42 exhibited Ca2+ mobilizing properties. The Aβ42-stimulated Ca2+ signals persisted in the absence of extracellular Ca2+ indicating a significant contribution of Ca2+ release from the ER Ca2+ store to the generation of these signals. Moreover, inositol 1,4,5-trisphosphate (InsP3) signaling contributed to Aβ42-stimulated Ca2+ release. The Ca2+ mobilizing effect of Aβ42 was also observed when applied to permeabilized cells deficient in InsP3 receptors revealing an additional direct effect of internalized Aβ42 upon the ER, and a mechanism for induction of toxicity by intracellular Aβ42

Quantitative digital imaging of banana growth suppression by plant parasitic nematodes

Open Access JournalA digital camera fitted with a hemispherical lens was used to generate canopy leaf area index (LAI) values for a banana (Musa spp.) field trial with the aim of establishing a method for monitoring stresses on tall crop plants. The trial in Uganda consisted of two cultivars susceptible to nematodes, a plantain, Gonja manjaya and an East African Highland banana, Mbwazirume, plus a nematode resistant dessert banana, Yangambi km5. A comparative approach included adding a mixed population of Radopholus similis, Helicotylenchus multicinctus and Meloidogyne spp. to the soil around half the plants of each cultivar prior to field planting. Measurements of LAI were made fortnightly from 106 days post-planting over two successive cropping cycles. The highest mean LAI during the first cycle for Gonja manjaya was suppressed to 74.863.5% by the addition of nematodes, while for Mbwazirume the values were reduced to 71.161.9%. During the second cycle these values were 69.262.2% and 72.262.7%, respectively. Reductions in LAI values were validated as due to the biotic stress by assessing nematode numbers in roots and the necrosis they caused at each of two harvests and the relationship is described. Yield losses, including a component due to toppled plants, were 35.3% and 55.3% for Gonja manjaya and 31.4% and 55.8% for Mbwazirume, at first and second harvests respectively. Yangambi km5 showed no decrease in LAI and yield in the presence of nematodes at both harvests. LAI estimated by hemispherical photography provided a rapid basis for detecting biotic growth checks by nematodes on bananas, and demonstrated the potential of the approach for studies of growth checks to other tall crop plants caused by biotic or abiotic stresses

Preference for Risk Management Information Sources: Implications for Extension and Outreach Programming

This article examines farmers’ preferences for various risk management information sources. Our results suggest that information from risk management experts, in-depth materials studied on their own, and popular press outlets tend to be preferred and are ranked highly by producers. Using a regression model to investigate farmer/farm attributes that affect preference for a particular risk management information source, we find that younger farmers with college education, higher leverage, assets greater than $1 million, risk-loving attitudes, and who have used professional services (marketing consultants) tend to prefer information from risk management experts, the Internet, and marketing clubs/other producers. On the other hand, producers who prefer self-study of educational materials and popular press information sources tend to be younger, with lower leverage levels, and have used fewer professional services.crop insurance, extension, information sources, outreach, risk management, Risk and Uncertainty,

Simple biophysics underpins collective conformations of the intrinsically disordered proteins of the Nuclear Pore Complex

Nuclear Pore Complexes (NPCs) are key cellular transporter that control nucleocytoplasmic transport in eukaryotic cells, but its transport mechanism is still not understood. The centerpiece of NPC transport is the assembly of intrinsically disordered polypeptides, known as FG nucleoporins, lining its passageway. Their conformations and collective dynamics during transport are difficult to assess in vivo. In vitro investigations provide partially conflicting results, lending support to different models of transport, which invoke various conformational transitions of the FG nucleoporins induced by the cargo-carrying transport proteins. We show that the spatial organization of FG nucleoporin assemblies with the transport proteins can be understood within a first principles biophysical model with a minimal number of key physical variables, such as the average protein interaction strengths and spatial densities. These results address some of the outstanding controversies and suggest how molecularly divergent NPCs in different species can perform essentially the same function

Information theory explanation of the fluctuation theorem, maximum entropy production and self-organized criticality in non-equilibrium stationary states

Jaynes' information theory formalism of statistical mechanics is applied to the stationary states of open, non-equilibrium systems. The key result is the construction of the probability distribution for the underlying microscopic phase space trajectories. Three consequences of this result are then derived : the fluctuation theorem, the principle of maximum entropy production, and the emergence of self-organized criticality for flux-driven systems in the slowly-driven limit. The accumulating empirical evidence for these results lends support to Jaynes' formalism as a common predictive framework for equilibrium and non-equilibrium statistical mechanics.Comment: 21 pages, 0 figures, minor modifications, version to appear in J. Phys. A. (2003

Using legume-based mixtures to enhance the nitrogen use efficiency and economic viability of cropping systems - Final report (LK09106/HGCA3447)

As costs for mineral fertilisers rise, legume-based leys are recognised as a potential alternative nitrogen source for crops. Here we demonstrate that including species-rich legume-based leys in rotations helps to maximise synergies between agricultural productivity and other ecosystem services. By using functionally diverse plant species mixtures, these services can be optimised and fine-tuned to regional and farm-specific needs. Replicated field experiments were conducted over three years at multiple locations, testing the performance of 12 legume species and 4 grass species sown in monocultures, as well as in a mixture of 10 of the legumes and all 4 grasses (called the All Species Mix, ASM). In addition, we compared this complex mixture to farmer-chosen ley mixtures on 34 sites across the UK. The trials showed that there is a large degree of functional complementarity among the legume species. No single species scored high on all evaluation criteria. In particular, the currently most frequently used species, white clover, is outscored by other legume species on a number of parameters such as early development and resistance to decomposition. Further complementarity emerged from the different responses of legume species to environmental variables, with soil pH and grazing or cutting regime being among the more important factors. For example, while large birdsfoot trefoil showed better performance on more acidic soils, the opposite was true for sainfoin, lucerne and black medic. In comparison with the monocultures, the ASM showed increased ground cover, increased above-ground biomass and reduced weed biomass. Benefits of mixing species with regard to productivity increased over time. In addition, the stability of biomass production across sites was greater in the ASM than in the legume monocultures. Within the on-farm trials, we further found that on soils low in organic matter the biomass advantage of the ASM over the Control ley was more marked than on the soils with higher organic matter content. Ecological modelling revealed that the three best multifunctional mixtures all contained black medic, lucerne and red clover. Within the long term New Farming Systems (NFS) rotational study, the use of a clover bi-crop showed improvement to soil characteristics compared to current practice (e.g. bulk density and water infiltration rate). Improvements in wheat yield were also noted with respect to the inclusion of a clover bi-crop in 2010, but there was evidence of a decline in response as the N dose was increased. Cumulatively, over both the wheat crop and the spring oilseed rape crop, the clover bi-crop improved margin over N. The highest average yield response (~9%) was associated with the ASM legume species mix cover cropping approach

Karyopherin enrichment and compensation fortifies the nuclear pore complex against nucleocytoplasmic leakage

Nuclear pore complexes (NPCs) discriminate nonspecific macromolecules from importin and exportin receptors, collectively termed "karyopherins" (Kaps), that mediate nucleocytoplasmic transport. This selective barrier function is attributed to the behavior of intrinsically disordered phenylalanine-glycine nucleoporins (FG Nups) that guard the NPC channel. However, NPCs in vivo are typically enriched with different Kaps, and how they impact the NPC barrier remains unknown. Here, we show that two major Kaps, importinβ1/karyopherinβ1 (Kapβ1) and exportin 1/chromosomal maintenance 1 (CRM1), are required to fortify NPC barrier function in vivo. Their enrichment at the NPC is sustained by promiscuous binding interactions with the FG Nups, which enable CRM1 to compensate for the loss of Kapβ1 as a means to maintain NPC barrier function. However, such a compensatory mechanism is constrained by the cellular abundances and different binding kinetics for each respective Kap, as evidenced for importin-5. Consequently, we find that NPC malfunction and nucleocytoplasmic leakage result from poor Kap enrichment

The proton and electron radiation belts at geosynchronous orbit: Statistics and behavior during high‐speed stream‐driven storms

The outer proton radiation belt (OPRB) and outer electron radiation belt (OERB) at geosynchronous orbit are investigated using a reanalysis of the LANL CPA (Charged Particle Analyzer) 8‐satellite 2‐solar cycle energetic particle data set from 1976 to 1995. Statistics of the OPRB and the OERB are calculated, including local time and solar cycle trends. The number density of the OPRB is about 10 times higher than the OERB, but the 1 MeV proton flux is about 1000 times less than the 1 MeV electron flux because the proton energy spectrum is softer than the electron spectrum. Using a collection of 94 high‐speed stream‐driven storms in 1976–1995, the storm time evolutions of the OPRB and OERB are studied via superposed epoch analysis. The evolution of the OERB shows the familiar sequence (1) prestorm decay of density and flux, (2) early‐storm dropout of density and flux, (3) sudden recovery of density, and (4) steady storm time heating to high fluxes. The evolution of the OPRB shows a sudden enhancement of density and flux early in the storm. The absence of a proton dropout when there is an electron dropout is noted. The sudden recovery of the density of the OERB and the sudden density enhancement of the OPRB are both associated with the occurrence of a substorm during the early stage of the storm when the superdense plasma sheet produces a “strong stretching phase” of the storm. These storm time substorms are seen to inject electrons to 1 MeV and protons to beyond 1 MeV into geosynchronous orbit, directly producing a suddenly enhanced radiation belt population.Key PointsDuring high‐speed stream‐driven storms, the electron and proton radiation belts are directly enhanced by a single substormThe enhancing substorm occurs during the “strong stretching” phase of the storm caused by the superdense plasma sheetProton and electron injection to 1 MeV is seen for these strong stretching phase substormsPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/133567/1/jgra52702.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/133567/2/jgra52702_am.pd

Promoter de-methylation of cyclin D2 by sulforaphane in prostate cancer cells

Sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables, induces potent anti-proliferative effects in prostate cancer cells. One mechanism that may contribute to the anti-proliferative effects of SFN is the modulation of epigenetic marks, such as inhibition of histone deacetylase (HDAC) enzymes. However, the effects of SFN on other common epigenetic marks such as DNA methylation are understudied. Promoter hyper-methylation of cyclin D2, a major regulator of cell cycle, is correlated with prostate cancer progression, and restoration of cyclin D2 expression exerts anti-proliferative effects on LnCap prostate cancer cells. Our study aimed to investigate the effects of SFN on DNA methylation status of cyclin D2 promoter, and how alteration in promoter methylation impacts cyclin D2 gene expression in LnCap cells. We found that SFN significantly decreased the expression of DNA methyltransferases (DNMTs), especially DNMT1 and DNMT3b. Furthermore, SFN significantly decreased methylation in cyclin D2 promoter regions containing c-Myc and multiple Sp1 binding sites. Reduced methlyation of cyclin D2 promoter corresponded to an increase in cyclin D2 transcript levels, suggesting that SFN may de-repress methylation-silenced cyclin D2 by impacting epigenetic pathways. Our results demonstrated the ability of SFN to epigenetically modulate cyclin D2 expression, and provide novel insights into the mechanisms by which SFN may regulate gene expression as a prostate cancer chemopreventive agent

Legume based plant mixtures for delivery of multiple ecosystem services: An overview of benefits

As costs for mineral fertilizers rise, legume-based leys are recognised as a potential alternative nitrogen source for crops. Here we demonstrate that including species-rich legume-based leys in the rotation helps to maximize synergies between agricultural productivity and other ecosystem services. By using functionally diverse plant species mixtures these services can be optimised and fine-tuned to regional and farm-specific needs. Field experiments run over three years at multiple locations showed that the stability of ley performance was greater in multi-species mixtures than in legume monocultures. In addition, mixing different legume species in the ley helps to suppress both early and late weeds. Further, combining complementary phenologies of different legume species extended forage availability for key pollinator species. Finally, widening the range of legume species increases opportunities to build short term leys into rotations on conventional farms via cover cropping or undersowing