Activation of p38 MAPK in the substantia nigra leads to nuclear translocation of NF-κB in MPTP-treated mice: implication in Parkinson's disease

Activation and translocation of the transcription factor nuclear factor kappa B (NF-κB) from cytoplasm to the nucleus has been reported in models of Parkinson's disease (PD). Our focus was to discern the upstream events which ultimately lead to NF-κB nuclear translocation using animal model of PD. We demonstrate that p38 activation results in downstream phosphorylation of NF-κB and accumulation of p65 subunit of NF-κB selectively in ventral midbrain but not in striatum. Treatment with p38 inhibitor, SB239063, prevented downstream phosphorylation of IκBα and p65 translocation to the nucleus in the ventral midbrain. Phosphorylation of anti-apoptotic Bcl2, an NF-κB target gene by p38 to inactive pBcl2ser87 was also attenuated by SB239063. Increased staining of p65 in the nuclei of cells in the substantia nigra but not in the ventral tegmental area of MPTP-treated mice further suggests a role for NF-κB in PD. In agreement with the above, sustained caspase activation is seen in the ventral midbrain but not in striatum. We demonstrate the region specific p38-mediated activation of NF-κB following MPTP treatment demonstrating the role of p38/NF-κB signaling in the pathogenesis and progression of the disease. Selective inhibitors of p38 may therefore, help preserve the surviving neurons in PD and slow down the disease progression

Numerical Simulation of the Ion Transport Behavior in Concrete under Coupled Axial Loading and Sulfate Attack

During a sulfate attack on concrete, ions, which are transported to the interior of concrete through pores, react with the concrete components. The transport characteristics are affected by various factors. A chemical-mechanical coupling method for accurately evaluating the transport behavior of sulfate ions in concrete under stress conditions was proposed in this study to investigate the transport characteristics of these ions. The diffusion-reaction equations of sulfate ions were obtained based on the diffusion-reaction approach in combination with the mechanism of volume expansion under a sulfate attack and the influence of load on the concrete voidage. The constitutive response and crack density of the matrix were calculated according to the volumetric strain caused by external load and ettringite growth. Then, the diffusion coefficient of the equation was dynamically corrected. T\u27his phenomenon was a strongly coupled moving boundary problem, and the equations were solved using numerical method. A case study was conducted to analyze the distribution law of ionic concentration and volumetric strain obtained using the proposed method. Results demonstrate that the crack damage due to volumetric strain plays a major role in the diffusion of sulfate ions. The load has minimal effect on the transport behavior under a low stress level, and the water-cement ratio is negatively correlated with ion transport capacity. The proposed method serves as a reference for evaluating the durability of an underground structure in a sulfate formation

Familial aggregation of early-onset cancers

This registry-linkage study evaluates familial aggregation of cancer among relatives of a population-based series of early-onset (Peer reviewe

Observations on the early public health movement in Scotland

The observations which follow represent a.n attempt to arrive at an understanding of certain aspects of the background to the early public health movement which seemed obscure. By all accounts the 18th century in Scotland represented a period of material progress and increasing prosperity. The economic advance continued in the early 19th century, yet the rise in the prosperity of the people did not seem to keep pace with it. The investigations into the conditions of the people in the 1830's, which played such an important part in the sanitary reform movement, indicated an actual deterioration in welfare for many of the common folk. This association of increasing economic power and diminishing prosperity seemed anomalous at first glance: and the fact of a break in the upward trend of general prosperity was difficult to accept without further study.in attempting to understand these difficulties, the first step was to examine events during the 18th century to find out whether the supposed improvement in the welfare of the people during that period was genuine. for this purpose the increase in population which took place during that century was selected for special study, and an attempt was made to discover the causes of this increase. The next step was to look into conditions in the early 19th century to find out whether or not a deterioration actually did take place at that time. Ioor this purpose certain trends of the death rates and the incidence of disease were examined: and the environment and financial condition of parts of the population were investigated. ï+finally an attempt was made to arrive at an understanding of the history of some of the early developments in public health reform in Scotland in the light of such facts as had been elucidated

The identification and significance of inputs to Anthrosols in North-West Europe

In recent years there has been a renewed interest in soils which are the result of past land management practices involving substantial additions of mineral and organic matter. However, there is still a substantial lack of detailed information on their formation. Anthrosols are distinguished by the presence of a deep top horizon and such soils were investigated at sites in Scotland, Denmark and The Netherlands. Field data and samples were collected from eight sites under arable cultivation, meadowland and woodland. Particle size distribution, pH, loss on ignition, ECEC, base saturation and total P were measured. Carbonaceous particles were identified through micromorphological analysis and the determination of O:C ratios using an electron microprobe. Despite the use of different inputs in recent centuries and different current land management, the resultant anthropogenic soils are remarkably similar in field and analytical properties. Nevertheless, subtle changes in particle size can be explained by parent material influences, material imported by farmers and by inputs by other processes such as by wind. The results from microprobe analysis demonstrate the importance of carbonaceous particles in storing phosphorus. Thus the inherent fertility of these Anthrosols can be explained in part by the application of carbonised material in the past