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

Predictors of Municipal Bankruptcies and State Intervention Programs: An Exploratory Study

Why do some struggling cities file for bankruptcy while others, facing simiar circumstances, do not? This Article builds on the literature examining the causes and consequences ofmunicipal fiscal distress by exploring specific factors that lead municipalities to seek help from the state and federal government. Viewing municipal opportunities and constraints through political, economic, and legal lenses, this Article helps to explain the nuances ofmunicival decision making. After identifiing eight factors that may serve as predctors of municipal insolvency, the authors studied cities in Fiscal distress with an eye toward uncovering the circumstances that led each of these cities into and—if applicable—out of their financial predicaments. Union density unfunded pension iabilty, and financial mismanagement were the three most prevalent factors in the authors\u27 sample population. The analysis suggests that scholars and policymakers should focus their efforts on using bankruptcy relief conjunction with state aid programs in order to address these primary sources of municipal distress in a more comprehensive manner

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

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,

Emerging Issues in Micro Finance Banks in Nigeria

Microfinance is an economic development strategy intended to provide financial services such as credit, savings, micro insurance micro leasing and payment services to the poor and low income client.  This paper shall be dealing with emerging issues in microfinance banks in Nigeria. This paper is divided into eleven sections.  Introduction, microfinance concept and needs, characteristics and ownership of microfinance banks microfinance banking in Nigeria will be discussed. The paper also discusses functions and number of licensed MFB’s, forms of lending and microfinancing challenges.  This paper concludes by recommending measures for improvement of microfinancing services in Nigeria

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

Optimisation of bitumen emulsion properties for ballast stabilisation

: Ballasted track, while providing economical and practical advantages, is associated with high costs and material consumption due to frequent maintenance. More sustainable alternatives to conventional ballasted trackbeds should therefore aim at extending its durability, particularly considering ongoing increases in traffic speed and loads. In this regard, the authors have investigated a solution consisting of bitumen stabilised ballast (BSB), designed to be used for new trackbeds as well as in reinforcing existing ones. This study presents the idea behind the technology and then focuses on a specific part of its development: the optimisation of bitumen emulsion properties and dosage in relation to ballast field conditions. Results showed that overall bitumen stabilisation improved ballast resistance to permanent deformation by enhancing stiffness and damping properties. Scenarios with higher dosage of bitumen emulsion, higher viscosity, quicker setting behaviour, and harder base bitumen seem to represent the most desirable conditions to achieve enhanced in-field performanc

Advances in Cartilage Tissue Engineering Using Bioinks with Decellularized Cartilage and Three-Dimensional Printing

Osteoarthritis, a chronic, debilitating, and painful disease, is one of the leading causes of disability and socioeconomic burden, with an estimated 250 million people affected worldwide. Currently, there is no cure for osteoarthritis and treatments for joint disease require improvements. To address the challenge of improving cartilage repair and regeneration, three-dimensional (3D) printing for tissue engineering purposes has been developed. In this review, emerging technologies are presented with an overview of bioprinting, cartilage structure, current treatment options, decellularization, bioinks, and recent progress in the field of decellularized extracellular matrix (dECM)–bioink composites is discussed. The optimization of tissue engineering approaches using 3D-bioprinted biological scaffolds with dECM incorporated to create novel bioinks is an innovative strategy to promote cartilage repair and regeneration. Challenges and future directions that may lead to innovative improvements to currently available treatments for cartilage regeneration are presented

Thermo-rheological analysis of WMA-additive modified binders

Thermo-rheological characteristics of unmodified and modified bitumen have significant impacts on the mechanical response of asphalt. This study investigates the impacts of an organic and a chemical Warm Mix Asphalt additive on bitumen thermo-rheological and mechanical characteristics. Modified binders with different concentrations of each additive were studied and analysed comparatively to a 40/60 penetration grade bitumen. Frequency sweep tests were performed at different ageing levels to characterise the Linear Viscoelastic properties. The multiple stress creep and recovery, linear amplitude sweep (LAS) and low temperature creep stiffness tests, together with the Glover–Rowe (G–R) fatigue parameter (determined from fitting of the 2S2P1D model to the complex shear modulus and phase angle master curves) were used to analyse the performance of the binders at critical operating temperatures. The results demonstrated the necessity to analyse the behavior of the studied binders beyond the limits of linear viscoelasticity to better characterise these types of bitumen. The results also indicated that both additives retarded bitumen ageing with the organic additive increasing bitumen elastic response while the chemical additive increased its viscous response. The results also showed an excellent correlation between the G–R parameter and LAS results which suggests the ability to use this parameter in characterising fatigue performance of the studied binders. This also suggests that bitumen fatigue life may be improving over time due to the increased elastic behahviour during ageing so long as a certain critical level of ageing is not reached