Granule Cell Dispersion in Human Temporal Lobe Epilepsy: Proteomics investigation of neurodevelopmental migratory pathways

Granule cell dispersion (GCD) is a common pathological feature observed in the hippocampus of patients with Mesial Temporal Lobe Epilepsy (MTLE). Pathomechanisms underlying GCD remain to be elucidated, but one hypothesis proposes aberrant reactivation of neurodevelopmental migratory pathways, possibly triggered by febrile seizures. This study aims to compare the proteomes of basal and dispersed granule cells in the hippocampus of eight MTLE patients with GCD to identify proteins that may mediate GCD in MTLE. Quantitative proteomics identified 1882 proteins, of which 29% were found in basal granule cells only, 17% in dispersed only and 54% in both samples. Bioinformatics analyses revealed upregulated proteins in dispersed samples were involved in developmental cellular migratory processes, including cytoskeletal remodelling, axon guidance and signalling by Ras homologous (Rho) family of GTPases (P<0.01). The expression of two Rho GTPases, RhoA and Rac1, was subsequently explored in immunohistochemical and in situ hybridisation studies involving eighteen MTLE cases with or without GCD, and three normal post mortem cases. In cases with GCD, most dispersed granule cells in the outer-granular and molecular layers have an elongated soma and bipolar processes, with intense RhoA immunolabelling at opposite poles of the cell soma, while most granule cells in the basal granule cell layer were devoid of RhoA. A higher density and percentage of cells expressing RhoA was observed in cases with GCD than without GCD (P<0.004). In GCD cases, the density and percentage of cells expressing RhoA was significantly higher in the inner molecular layer than granule cell layer (P<0.026), supporting proteomic findings. In situ hybridisation studies using probes against RHOA and RAC1 mRNAs revealed fine peri- and nuclear puncta in granule cells of all cases. The density of cells expressing RHOA mRNAs were significantly higher in the inner molecular layer of cases with GCD than without GCD(P=0.05). In summary, our study has found limited evidence for ongoing adult neurogenesis in the hippocampus of patients with MTLE, but evidence of differential dysmaturation between dispersed and basal granule cells has been demonstrated, and elevated expression of Rho GTPases in dispersed granule cells may contribute to the pathomechanisms underpinning GCD in MTLE

TRADE LIBERALISATION UNDER THE DOHA DEVELOPMENT AGENDA; OPTIONS AND CONSEQUENCES FOR AFRICA

This study provides a quantitative estimate of the potential economic consequences of multilateral trade reform under the WTO for Africa using a framework that explicitly incorporates issues of concern to the region, such as preference erosion, loss of tariff revenue, and trade facilitation. It also examines the impact of OECD agricultural support programmes on economic welfare and specialisation in Africa. In the static version of the GTAP model, the study finds that full liberalisation of trade would increase global welfare (income) by 0.3 per cent, but would add 0.7 per cent annually to income in the African region. Sub-Saharan Africa and, to a lesser extent, Southern Africa, are vulnerable to partial trade reforms as they incur losses from partial reform while all other regions derive positive gains from a liberalisation of minor scope.International Relations/Trade,

Fracture and fatigue strength of grouted macadams

Grouted macadams form a class of material which provides significant advantages in comparison to both concrete and conventional asphalt, having both rut resistance and a degree of flexibility. This paper presents a series of laboratory tests on several grouted macadam mixtures, for stiffness, fatigue and low temperature fracture. The variables explored include binder grade and content, aggregate size and gradation, and grout strength. Although the material is found to perform fundamentally as an asphalt, there are several significant differences in the form of fatigue behavior found compared to that usually expected from an asphalt. In particular the effect of varying binder content is found to be markedly different. The results are discussed in terms of optimizing mixture design in order to obtain the most desirable combination of properties (stiffness, fatigue strength, low temperature fracture resistance). Discussion is also presented regarding the possible role of grouted macadams as base or binder courses within highway pavements, and the conclusion is drawn that they are likely to provide an economical solution in many circumstances owing to their superior mechanical properties

Bivariant algebraic K-Theory

We show how methods from K-theory of operator algebras can be applied in a completely algebraic setting to define a bivariant, matrix-stable, homotopy-invariant, excisive K-theory of algebras over a fixed unital ground ring H, kk_*(A,B), which is universal in the sense that it maps uniquely to any other such theory. It turns out kk is related to C. Weibel's homotopy algebraic K-theory, KH. We prove that, if H is commutative and A is central as an H-bimodule, then kk_*(H,A)=KH_*(A). We show further that some calculations from operator algebra KK-theory, such as the exact sequence of Pimsner-Voiculescu, carry over to algebraic kk.Comment: 40 pages, no figures. Comparison with Kassel's K-group added (see 6.7). Final version to appear in Crelle's Journal, including galley proof correction

A Lipid-Rich Gestational Diet Predisposes Offspring to Nonalcoholic Fatty Liver Disease: A Potential Sequence of Events

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome. It affects 20%–30% of the US population, and it is increasing worldwide. Recently, the role of lipid-rich maternal gestational nutrition in spurring the development of NAFLD among offspring has been indicated. Fetal predisposition to NAFLD involves numerous physiological reroutings that are initiated by increased delivery of nonesterified fatty acids to the fetal liver. Hampered ß-oxidation, uncontrolled oxidative stress, increased triacylglycerol synthesis, and the endoplasmic reticulum unfolded protein response are all implicated in sculpting a hepatic phenotype with a propensity to develop NAFLD in the postnatal state. This review suggests a mechanism that integrates outcomes reported by a variety of studies conducted in an analysis of fetal hepatic metabolic capacity amid the maternal consumption of a high-fat diet. Potential preventive measures and therapies for use both as part of prenatal nutrition and for those at risk for the development of NAFLD are also discussed

The effect of using rest periods in 4PB tests on the fatigue life of grouted macadams

Four-point bending tests are commonly used to assess the fatigue resistance of bi-tuminous bound materials that are used in road pavements. However, it is difficult to establish a reliable relationship between the laboratory test results and the field performance of the mate-rial. In order to predict the real life of the pavement, shift factors are normally used to convert the fatigue results obtained in the laboratory onto the actual fatigue life of the material in the field. Those shift factors depend on the type of test used, the testing conditions and the type of mixture used. In this study, an attempt was made to establish a shift factor for grouted mac-adams, based on four-point bending fatigue test results carried out with rest periods between the loading cycles. The result obtained was used to define a fatigue criterion for pavement design with grouted macadams

Catastrophic regime shifts in model ecological communities are true phase transitions

Ecosystems often undergo abrupt regime shifts in response to gradual external changes. These shifts are theoretically understood as a regime switch between alternative stable states of the ecosystem dynamical response to smooth changes in external conditions. Usual models introduce nonlinearities in the macroscopic dynamics of the ecosystem that lead to different stable attractors among which the shift takes place. Here we propose an alternative explanation of catastrophic regime shifts based on a recent model that pictures ecological communities as systems in continuous fluctuation, according to certain transition probabilities, between different micro-states in the phase space of viable communities. We introduce a spontaneous extinction rate that accounts for gradual changes in external conditions, and upon variations on this control parameter the system undergoes a regime shift with similar features to those previously reported. Under our microscopic viewpoint we recover the main results obtained in previous theoretical and empirical work (anomalous variance, hysteresis cycles, trophic cascades). The model predicts a gradual loss of species in trophic levels from bottom to top near the transition. But more importantly, the spectral analysis of the transition probability matrix allows us to rigorously establish that we are observing the fingerprints, in a finite size system, of a true phase transition driven by background extinctions.Comment: 19 pages, 11 figures, revised versio

Structure of naturally hydrated ferrihydrite revealed through neutron diffraction and first-principles modeling

Ferrihydrite, with a ‘‘two-line’’ x-ray diffraction pattern (2L-Fh), is the most amorphous of the iron oxides and is ubiquitous in both terrestrial and aquatic environments. It also plays a central role in the regulation and metabolism of iron in bacteria, algae, higher plants, and animals, including humans. In this study, we present a single-phase model for ferrihydrite that unifies existing analytical data while adhering to fundamental chemical principles. The primary particle is small (20–50 Å) and has a dynamic and variably hydrated surface, which negates long-range order; collectively, these features have hampered complete characterization and frustrated our understanding of the mineral's reactivity and chemical/biochemical function. Near and intermediate range neutron diffraction (NIMROD) and first-principles density functional theory (DFT) were employed in this study to generate and interpret high-resolution data of naturally hydrated, synthetic 2L-Fh at standard temperature. The structural optimization overcomes transgressions of coordination chemistry inherent within previously proposed structures, to produce a robust and unambiguous single-phase model