Striatal Synaptic Dysfunction and Hippocampal Plasticity Deficits in the Hu97/18 Mouse Model of Huntington Disease

Huntington disease (HD) is a fatal neurodegenerative disorder caused by a CAG repeat expansion in the gene (HTT) encoding the huntingtin protein (HTT). This mutation leads to multiple cellular and synaptic alterations that are mimicked in many current HD animal models. However, the most commonly used, well-characterized HD models do not accurately reproduce the genetics of human disease. Recently, a new ‘humanized’ mouse model, termed Hu97/18, has been developed that genetically recapitulates human HD, including two human HTT alleles, no mouse Hdh alleles and heterozygosity of the HD mutation. Previously, behavioral and neuropathological testing in Hu97/18 mice revealed many features of HD, yet no electrophysiological measures were employed to investigate possible synaptic alterations. Here, we describe electrophysiological changes in the striatum and hippocampus of the Hu97/18 mice. At 9 months of age, a stage when cognitive deficits are fully developed and motor dysfunction is also evident, Hu97/18 striatal spiny projection neurons (SPNs) exhibited small changes in membrane properties and lower amplitude and frequency of spontaneous excitatory postsynaptic currents (sEPSCs); however, release probability from presynaptic terminals was unaltered. Strikingly, these mice also exhibited a profound deficiency in long-term potentiation (LTP) at CA3-to-CA1 synapses. In contrast, at 6 months of age we found only subtle alterations in SPN synaptic transmission, while 3-month old animals did not display any electrophysiologically detectable changes in the striatum and CA1 LTP was intact. Together, these data reveal robust, progressive deficits in synaptic function and plasticity in Hu97/18 mice, consistent with previously reported behavioral abnormalities, and suggest an optimal age (9 months) for future electrophysiological assessment in preclinical studies of HD.     

Grass,mosses, algae,or leaves? Food preference among shredders from open-canopy streams

Shredder feeding is a vital process in making decomposition products available to biota in streams. To investigate which food sources shredders in open-canopy streams exploit, we conducted a feeding preference experiment with the invertebrate detritivores Limnephilus bipunctatus and Nemoura sp., which are commonly found in open-canopy streams on the Swedish island of Öland in the southern Baltic Sea. Leaves of birch, Swedish whitebeam, and shrubby cinquefoil; dead and fresh grass; water moss; and algae were offered to the shredders in multi- and single treatments. We hypothesized that food with high nutritional value would be preferred. Both taxa preferred leaves of shrubby cinquefoil, a bush common in the riparian zone of Öland streams; additionally Nemoura sp. also chose algae. Dead grass, the most abundant food source in the streams during the whole year, was the least consumed food type. The fresh food types had highest nutritional value, measured as carbon to nitrogen content. Therefore, food quality could not alone explain the preference of shrubby cinquefoil. However, among the detritus type offered, shrubby cinquefoil had the highest nutritional value. Shrubby cinquefoil may constitute one important energy source to these open-canopy stream ecosystems and may be essential in maintaining an abundant shredder community in these streams. Thus, the results of this study indicate that detrital resources are indeed important in open-canopy stream systems.     

Contrasting effects of extracts from invasive Reynoutria japonica on soil microbial biomass,activity, and community structure

Invasive plants may modify soil properties through the release of phenolic compounds. The effects of phenolics produced by a noxious invader, Reynoutria japonica, on soil microorganisms have rarely been studied in experimental conditions. We performed a laboratory experiment to assess the influence of extracts from R. japonica on soil microbial activity, biomass, and community structure. Two types of extracts (shoots and rhizomes) were added in four concentrations (control—no extract, low—extract diluted 100 times, medium—extract diluted ten times, and high—undiluted extract) to soil collected under native plant species. Concentrations of 12 phenolic compounds, namely catechin, chlorogenic acid, emodin, epicatechin, hyperoside, quercetin, physcion, piceatannol, polydatin, procyanidin B3, resveratrol, and resveratroloside were analyzed in the extract and soil. We measured the activity of five enzymes, namely acid and alkaline phosphatases, β-glucosidase, phenoloxidase, peroxidase, the activity of bacteria on Biolog Ecoplates, as well as the biomass of bacteria, saprotrophic fungi, arbuscular mycorrhizal fungi (AMF), and microbial community structure using phospholipid (PLFA) and neutral (NLFA) fatty acid analysis. Many microbial parameters, namely phosphatase activities, total microbial, AMF, and G?+?bacterial biomass, were reduced following the addition of extracts. This was likely related to phenolics as concentrations of these compounds in soil increased with the concentration of extract added. In contrast, saprotrophic fungi and G- bacteria were largely positively affected by extract addition. Shoot and rhizome extracts had relatively similar effects on the soil properties. The changes in soil biota caused by R. japonica invasion may have implications for restoration of invaded areas.

     

Regionalisation of the mouse visceral endoderm as the blastocyst transforms into the egg cylinder

Background  

Reciprocal interactions between two extra-embryonic tissues, the extra-embryonic ectoderm and the visceral endoderm, and the pluripotent epiblast, are required for the establishment of anterior-posterior polarity in the mouse. After implantation, two visceral endoderm cell types can be distinguished, in the embryonic and extra-embryonic regions of the egg cylinder. In the embryonic region, the specification of the anterior visceral endoderm (AVE) is central to the process of anterior-posterior patterning. Despite recent advances in our understanding of the molecular interactions underlying the differentiation of the visceral endoderm, little is known about how cells colonise the three regions of the tissue.     

Loss of Drosophila Vps16A enhances autophagosome formation through reduced Tor activity

The HOPS tethering complex facilitates autophagosome-lysosome fusion by binding to Syx17 (Syntaxin 17), the autophagosomal SNARE. Here we show that loss of the core HOPS complex subunit Vps16A enhances autophagosome formation and slows down Drosophila development. Mechanistically, Tor kinase is less active in Vps16A mutants likely due to impaired endocytic and biosynthetic transport to the lysosome, a site of its activation. Tor reactivation by overexpression of Rheb suppresses autophagosome formation and restores growth and developmental timing in these animals. Thus, Vps16A reduces autophagosome numbers both by indirectly restricting their formation rate and by directly promoting their clearance. In contrast, the loss of Syx17 blocks autophagic flux without affecting the induction step in Drosophila.     

Synthesis of N²-modified 7-methylguanosine 5'-monophosphates as nematode translation inhibitors

Preparative scale synthesis of 14 new N(2)-modified mononucleotide 5' mRNA cap analogues was achieved. The key step involved use of an S(N)Ar reaction with protected 2-fluoro inosine and various primary and secondary amines. The derivatives were tested in a parasitic nematode, Ascaris suum, cell-free system as translation inhibitors. The most effective compound with IC(50) ～0.9μM was a N(2)-p-metoxybenzyl-7-methylguanosine-5'-monophosphate 35.     

Midgut bacterial dynamics in Aedes aegypti

In vector mosquitoes, the presence of midgut bacteria may affect the ability to transmit pathogens. We have used a laboratory colony of Aedes aegypti as a model for bacterial interspecies competition and show that after a blood meal, the number of species (culturable on Luria-Bertani agar) that coexist in the midgut is low and that about 40% of the females do not harbor any cultivable bacteria. We isolated species belonging to the genera Bacillus, Elizabethkingia, Enterococcus, Klebsiella, Pantoea, Serratia, and Sphingomonas, and we also determined their growth rates, antibiotic resistance, and ex vivo inhibition of each other. To investigate the possible existence of coadaptation between midgut bacteria and their host, we fed Ae.?aegypti cohorts with gut bacteria from human, a frog, and two mosquito species and followed the bacterial population growth over time. The dynamics of the different species suggests coadaptation between host and bacteria, and interestingly, we found that Pantoea stewartii isolated from Ae.?aegypti survive better in Ae.?aegypti as compared to P.?stewartii isolated from the malaria mosquito Anopheles gambiae.     

Chloroplasts of Arabidopsis are the source and a primary target of a plant-specific programmed cell death signaling pathway

Enhanced levels of singlet oxygen ((1)O(2)) in chloroplasts trigger programmed cell death. The impact of (1)O(2) production in chloroplasts was monitored first in the conditional fluorescent (flu) mutant of Arabidopsis thaliana that accumulates (1)O(2) upon a dark/light shift. The onset of (1)O(2) production is rapidly followed by a loss of chloroplast integrity that precedes the rupture of the central vacuole and the final collapse of the cell. Inactivation of the two plastid proteins EXECUTER (EX1) and EX2 in the flu mutant abrogates these responses, indicating that disintegration of chloroplasts is due to EX-dependent signaling rather than (1)O(2) directly. In flu seedlings, (1)O(2)-mediated cell death signaling operates as a default pathway that results in seedlings committing suicide. By contrast, EX-dependent signaling in the wild type induces the formation of microlesions without decreasing the viability of seedlings. (1)O(2)-mediated and EX-dependent loss of plastid integrity and cell death in these plants occurs only in cells containing fully developed chloroplasts. Our findings support an as yet unreported signaling role of (1)O(2) in the wild type exposed to mild light stress that invokes photoinhibition of photosystem II without causing photooxidative damage of the plant.