Epigenetics involvement in Parkinson’s disease and manganese-induced neurotoxicity

Parkinson's disease (PD) is a progressive neurological disorder of CNS and one of the most common neurodegenerative diseases. The exact mechanisms underlying PD has been unclear but it is believed that multiple factors are involved. Excessive exposure to manganese (Mn) can causes its accumulation in the human brain and subsequent neural damage and even development of PD-like movement disorder, referred to as manganism. Although recent studies indicated the pathologic and clinical distinction between PD and Mn-induced neurotoxicity, genetically they have been shown some common features and associations. In recent years, the role of epigenetic changes has been well studied in brain development as well as different brain diseases including PD. Meanwhile, environmental agents including Mn have been found to damage the developing and mature nervous system through altering epigenetic regulatory pathways such as DNA methylation. The aim of this contribution was to review the epigenetic involvement in the etiology of PD and Mn-induced neurotoxicity. Other aspects of these syndromes were also discussed. Several lines of evidence have indicated that epigenetic modulation of gene plays more important roles in PD processes. On the other hand, Maternal Mn exposure has been found to be able to cause epigenetic changes in genes associated with neurodegeneration. The current data is very limited to show the association of MN-induced epigenetic changes and PD etiology. Although conclusion about the relationship between PD and Mn exposure need more consolidated studies, studying the molecular mechanisms of the effect of Mn, genetically and epigenetically will be helpful to understand the etiology of PD which is essential for therapeutic strategies of this disease

CHEMICAL SYNTHESIS AND BIOLOGICAL EVALUATION OF INHIBITORS AND SUBSTRATE OF CYTOSOLIC PHOSPHOLIPASE A2

Ph.DDOCTOR OF PHILOSOPH

Structural Color 3D Printing By Shrinking Photonic Crystals

The rings, spots and stripes found on some butterflies, Pachyrhynchus weevils, and many chameleons are notable examples of natural organisms employing photonic crystals to produce colorful patterns. Despite advances in nanotechnology, we still lack the ability to print arbitrary colors and shapes in all three dimensions at this microscopic length scale. Commercial nanoscale 3D printers based on two-photon polymerization are incapable of patterning photonic crystal structures with the requisite ~300 nm lattice constant to achieve photonic stopbands/ bandgaps in the visible spectrum and generate colors. Here, we introduce a means to produce 3D-printed photonic crystals with a 5x reduction in lattice constants (periodicity as small as 280 nm), achieving sub-100-nm features with a full range of colors. The reliability of this process enables us to engineer the bandstructures of woodpile photonic crystals that match experiments, showing that observed colors can be attributed to either slow light modes or stopbands. With these lattice structures as 3D color volumetric elements (voxels), we printed 3D microscopic scale objects, including the first multi-color microscopic model of the Eiffel Tower measuring only 39-microns tall with a color pixel size of 1.45 microns. The technology to print 3D structures in color at the microscopic scale promises the direct patterning and integration of spectrally selective devices, such as photonic crystal-based color filters, onto free-form optical elements and curved surfaces

Combining time and position dependent effects on a single machine subject to rate-modifying activities

We introduce a general model for single machine scheduling problems, in which the actual processing times of jobs are subject to a combination of positional and time-dependent effects, that are job-independent but additionally depend on certain activities that modify the processing rate of the machine, such as, maintenance. We focus on minimizing two classical objectives: the makespan and the sum of the completion times. The traditional classification accepted in this area of scheduling is based on the distinction between the learning and deterioration effects on one hand, and between the positional effects and the start-time dependent effects on the other hand. Our results show that in the framework of the introduced model such a classification is not necessary, as long as the effects are job-independent. The model introduced in this paper covers most of the previously known models. The solution algorithms are developed within the same general framework and their running times are no worse than those available earlier for problems with less general effects

Asymptomatic members with SOD1 mutation in a large kindred with familial amyotrophic lateral sclerosis have abnormal water diffusion characterisitcs

DTI was carried out in FALS/SALS patients and familial members with SOD1 mutation (AFALS) who may be in a pre-symptomatic phase of ALS. The changes in FA and TT were investigated in CBT/CST and in whole brain. In FALS/SALS, diffusion pattern changes were found in cerebral peduncle, internal capsule, sub-cortical white matter, cerebellum and frontal lobe while in AFALS, abnormal pattern could also be detected in the cerebral peduncle, cerebellum and frontal lobe but with a smaller extent. Our study indicates that DTI can show early diffusion changes in members with SOD1 mutation in FALS prior to symptom-onset.published_or_final_versio

Ankle-Brachial Index Is a Powerful Predictor of Renal Outcome and Cardiovascular Events in Patients with Chronic Kidney Disease

Ankle-brachial index (ABI) is an accurate tool to diagnose peripheral arterial disease. The aim of this study was to evaluate whether ABI is also a good predictor of renal outcome and cardiovascular events in patients with chronic kidney disease (CKD). We enrolled 436 patients with stage 3–5 CKD who had not been undergoing dialysis. Patients were stratified into two groups according to the ABI value with a cut point of 0.9. The composite renal outcome, including doubling of serum creatinine level and commencement of dialysis, and the incidence of cardiovascular events were compared between the two groups. After a median follow-up period of 13 months, the lower ABI group had a poorer composite renal outcome (OR = 2.719, P = 0.015) and a higher incidence of cardiovascular events (OR = 3.260, P = 0.001). Our findings illustrated that ABI is a powerful predictor of cardiovascular events and renal outcome in patients with CKD