Epilepsy genetics: An abundance of riches for biologists

AbstractTwenty-five genes have been identified in which mutations cause epileptic seizures in mice. The gene for a Na+/H+ exchanger has recently been found to underlie the spontaneous mutant slow wave epilepsy. Studies of such mutants should help elucidate the mechanisms that control neuronal excitability

Does Epileptiform Activity Contribute to Cognitive Impairment in Alzheimer's Disease?

Alzheimer's disease is a devastating neurological disorder. The role of hyperexcitability in the disease's cognitive decline is not completely understood. In this issue of Neuron, Palop et al. report both limbic seizures and presumed homeostatic responses to seizures in an animal model of Alzheimer's

Performance incentives and information communication technologies in Ugandan agricultural extension service delivery

Agriculture is the backbone of many countries in sub-Saharan Africa. Yet, lack of efficient extension systems to support agricultural development is widely seen as a missing link in agricultural transformation in the region. International development agencies have in the past four decades invested heavily in various extension models such as the Training and Visit and Farmer Field School systems in order to enhance the performance of extension workers. Despite such investments, the performance of extension agents does remain suboptimal in many contexts. Studies in other sectors show that incentivizing worker performance through nudges such as incentive realignment schemes that tie worker performance to a pay/bonus system could enhance worker productivity. However, there is a lack of incentive realignment studies that estimate the performance of extension agents insub-Saharan Africa. A potential hindrance to the application of such scheme to extension is the absence of monitoring mechanisms to track the performance of extension agents who often work across diverse local contexts to reach smallholder farmers with extension advice. This study empirically estimates the effect of an information communication technology (ICT)-based payment incentive system that tracks the performance of extension workers in rural Uganda. It undertakes a quasi-experimental ex-post impact assessment of a payment incentive realignment as an exogenous shift in the price of labor for extension services by Ugandan Community Knowledge Workers (CKWs) in 2011. This study applies a difference–in–difference with propensity score matching technique to estimate the effect of an ICT-based incentive re-alignment scheme in 2011, on the performance of 461 CKWs in rural Uganda. The study shows that CKWs in rural Uganda respond positively to an ICT-based performance incentive scheme that affects the price of labor. Results suggest that such performance systems can enhance the productivity of CKWs – an exemplar of rural extension agents in Uganda and elsewhere in developing countries. It also finds that younger CKWs respond more productively to higher incentives than their older counterparts. Therefore, the study suggests that extension policies that tie extension agents’ performance to ICT-based payment incentives could enhance their performance and contribute towards the sustainable developments goals on food security, among others, through multiplier effects.Keywords: Agricultural extension, community knowledge workers, ICT-based performance incentive

Structure Property Relationships in Organic Conjugated Systems

A series of π conjugated oligomers were studied by absorption and photoluminescence spectroscopy. A linear relationship between the positioning of the absorption and photoluminescence maxima plotted against inverse conjugation length is observed. The relationships are in good agreement with the simple particle in a box method, one of the earliest descriptions of the properties of one-dimensional organic molecules. In addition to the electronic transition energies, it was observed that the Stokes shift also exhibited a well-defined relationship with increasing conjugation length, implying a correlation between the electron-vibrational coupling and chain length. This correlation is further examined using Raman spectroscopy, whereby the integrated Raman scattering is seen to behave superlinearly with chain length. There is a clear indication that the vibrational activity and thus nonradiative decay processes are controllable through molecular structure. The correlations between the Stokes energies and the vibrational structure are also observed in a selection of PPV based polymers and a clear trend of increasing luminescence efficiency with decreasing vibrational activity and Stokes shift is observable. The implications of such structure property relationships in terms of materials design are discussed

Synthesis, characterisation and photo-stability of a folate-modified β-cyclodextrin as a functional food additive.

A novel two-step synthetic route was developed and gave the mono-substituted derivative 6-deoxy-6-[(1-(2-amino)ethylamino)folate]-b-cyclodextrin (CDEnFA) with high yield (60 %). Elemental analysis, mass spectrometry, 1H and 13C NMR, FTIR and Raman spectroscopies demonstrated the successful synthesis of the γ isomer only with no evidence of the presence of other isomers or free folic acid. Electronic absorption spectroscopy was used to study the photochemical properties of CDEnFA and showed that in both the solid state and aqueous solution CDEnFA is considerably more photo-stable than free folic acid

Detection vs selection: integration of genetic, epigenetic and environmental cues in fluctuating environments

ArticleThere are many inputs during development that influence an organism's fit to current or upcoming environments. These include genetic effects, transgenerational epigenetic influences, environmental cues and developmental noise, which are rarely investigated in the same formal framework. We study an analytically tractable evolutionary model, in which cues are integrated to determine mature phenotypes in fluctuating environments. Environmental cues received during development and by the mother as an adult act as detection-based (individually observed) cues. The mother's phenotype and a quantitative genetic effect act as selection-based cues (they correlate with environmental states after selection). We specify when such cues are complementary and tend to be used together, and when using the most informative cue will predominate. Thus, we extend recent analyses of the evolutionary implications of subsets of these effects by providing a general diagnosis of the conditions under which detection and selection-based influences on development are likely to evolve and coexist.This work was supported by a Leverhulme Trust International Network Grant to the four authors and by a grant from the Swedish Research Council (621-2010-5437) to O.L

Estrogen plus estrogen receptor antagonists alter mineral production by osteoblasts in vitro.

In early postmenopausal women, estrogen withdrawal is associated with increased bone turnover leading to bone loss and increased risk of fracture. Recent studies have suggested that the remaining bone tissue is significantly stronger, stiffer and has an increased tissue-level mineral content. Such changes may occur to compensate for bone loss or as a direct result of estrogen deficiency. To date many details of the physiology of osteoblastic cells during estrogen deficiency are vague. In this study we test the hypothesis that osteoblastic matrix mineralisation is altered at the onset of estrogen deficiency. In vitro cell culture experiments were carried out up to 28 days to compare the mineral production of MC3T3-E1 osteoblastic cells subject to estrogen deficiency (fulvestrant), enhanced estrogen supplementation (17-β-estradiol) or a combination of both. Mineralisation was detected using von Kossa staining and was quantified with alizarin red absorbance readings. The expression of osteocalcin and osteopontin proteins, markers of osteoblast differentiation and mineralisation, was monitored using immunohistochemistry. Our results demonstrate that estrogen enhancement improves matrix mineralisation by MC3T3 cells in vitro. Furthermore this study found a significant reduction in the level of mineralisation when cells were treated with a combination of estrogen and fulvestrant. In an estrogen deficient environment mineralisation by osteoblastic cells was not altered. These findings suggest that altered tissue mineralisation following estrogen deficiency is not a direct result of estrogen deficiency on osteoblasts. Rather, we propose that altered tissue mineralisation may be a compensatory mechanism by bone to counter bone loss and reduced strength

Ecological genetic conflict: Genetic architecture can shift the balance between local adaptation and plasticity

This is the author accepted manuscript. The final version is available from University of Chicago Press via the DOI in this record.Genetic polymorphism can contribute to local adaptation in heterogeneous habitats, for instance as a single locus with alleles adapted to different habitats. Phenotypic plasticity can also contribute to trait variation across habitats, through developmental responses to habitat-specific cues. We show that the genetic architecture of genetically polymorphic and plasticity loci may influence the balance between local adaptation and phenotypic plasticity. These effects of genetic architecture are instances of ecological genetic conflict. A reduced effective migration rate for genes tightly linked to a genetic polymorphism provides an explanation for the effects, and they can occur both for a single trait and for a syndrome of co-adapted traits. Using individualbased simulations and numerical analysis, we investigate how among-habitat genetic polymorphism and phenotypic plasticity depend on genetic architecture. We also study the evolution of genetic architecture itself, in the form of rates of recombination between genetically polymorphic loci and plasticity loci. Our main result is that for plasticity genes that are unlinked to loci with between-habitat genetic polymorphism, the slope of a reaction norm is steeper in comparison with the slope favored by plasticity genes that are tightly linked to genes for local adaptation.This work was supported by grants from the Carl Trygger Foundation (CTS 15292) to OL and by a Leverhulme Trust International Network Grant to SRXD, PH, OL, and JMM

Seasonal and Spatial Patterns Differ Between Intracellular and Extracellular Antibiotic Resistance Genes in Urban Stormwater Runoff

Antibiotic resistance is a public health threat that is exacerbated by the dispersion of antibiotic resistance genes (ARGs) into aquatic environments. Urban stormwater runoff has been recognized as a source of and a mechanism by which intracellular ARGs (iARGs) can be transported into receiving environments. The prevalence and behavior of extracellular ARGs (eARGs) in stormwater, however, has yet to be considered. This study quantified four iARGs and eARGs under baseflow and stormflow conditions. Urban stormwater runoff was found to be a source of all the ARGs examined, with the absolute concentration of all iARGs and two eARGs (ermF and tetC) increasing significantly (p \u3c 0.05) between baseflow and stormflow. The occurrence of iARGs and eARGs in stormwater runoff was also investigated across three seasons to differentiate temporal trends. All eARGs were found to be most abundant in the fall, while the iARGs did not display a consistent seasonal trend. Following, spatial patterns of the ARGs were elucidated by targeting four sampling locations, including direct runoff from a curbside storm inlet and a stormwater outfall, and two receiving environments, the Menomonee River and Lake Michigan. Stormwater was found to have the largest impact, in terms of the percent increase in ARG concentrations between baseflow and stormflow, on the outfall location where on average the iARGs and eARGs increased 16% and 12.3%, respectively. The variability in seasonal and spatial trends between the iARGs and eARGs suggests a difference in sources and transport mechanisms of the ARGs into the environment. Moreover, the results of this study revealed that eARGs are relevant contaminants to consider when determining the threat of antibiotic resistance originating from stormwater runoff