Though emerging evidence indicates that the pathogenesis of Parkinson's disease is strongly correlated to the accumulation and transmission of α-synuclein (α-syn) aggregates in the midbrain, no anti-aggregation agents have been successful at treating the disease in the clinic. Here, we show that graphene quantum dots (GQDs) inhibit fibrillization of α-syn and interact directly with mature fibrils, triggering their disaggregation. Moreover, GQDs can rescue neuronal death and synaptic loss, reduce Lewy body and Lewy neurite formation, ameliorate mitochondrial dysfunctions, and prevent neuron-to-neuron transmission of α-syn pathology provoked by α-syn preformed fibrils. We observe, in vivo, that GQDs penetrate the blood-brain barrier and protect against dopamine neuron loss induced by α-syn preformed fibrils, Lewy body/Lewy neurite pathology and behavioural deficits.

We have demonstrated that ab initio fast folding simulations at 400 K using a GB implicit solvent model with an all-atom based force field can describe the spontaneous formation of nativelike structures for the 36-residue villin headpiece and the 46-residue fragment B of Staphylococcal protein A. An implicit solvent model combined with high-temperature MD makes it possible to perform direct folding simulations of small- to medium-sized proteins by reducing the computational requirements tremendously. In the early stage of folding of the villin headpiece and protein A, initial hydrophobic collapse and rapid formation of helices were found to play important roles. For protein A, the third helix forms first in the early stage of folding and exhibits higher stability. The free energy profiles calculated from the folding simulations suggested that both of the helix-bundle proteins show a two-state thermodynamic behavior and protein A exhibits rather broad native basins.

Articles you may be interested inModel system-bath Hamiltonian and nonadiabatic rate constants for proton-coupled electron transfer at electrode-solution interfaces

ObjectiveTo determine the incidence and etiologies of celiac axis stenosis in asymptomatic individuals.Materials and MethodsThis prospective study involved 400 consecutive patients (male: 319, female: 81) referred to us for celiac arteriography between April and July 1999. When celiac axis branches were opacified by collateral circulation during superior mesenteric arteriography, the presence of celiac axis stenosis was suspected; lateral projection celiac arteriography was performed and the pressure gradient was measured. The indicators used to determine whether or not celiac axis stenosis was significant were luminal narrowing of more than 50% and a resultant pressure gradient of at least 10 mmHg. Its etiology was determined on the basis of angiographic appearances and CT findings.ResultsTwenty-nine patients (7.3%) had celiac axis stenosis. The etiology of the condition was extrinsic compression due to the median arcuate ligament in 16 patients (55%) and atherosclerosis in three (10%), while in ten (35%) it was not determined. The incidence of celiac axis stenosis did not vary significantly according to sex, age and the presence of calcified aortic plaque representing atherosclerosis.ConclusionThe incidence of hemodynamically significant celiac axis stenosis in this asymptomatic Korean population was 7.3% and the most important etiology was extrinsic compression by the median arcuate ligament of the diaphragm. Atherosclerosis was only a minor cause of the condition.

We report the results of theoretical studies on the self-assembled monolayers of benzenethiolate (BT) and benzyl mercaptide (BZM) on a Au(111) surface. A few relevant potential energy parameters were determined. We have performed annealing type molecular dynamics simulations where the minimized initial configurations are heated to 1000 K and then cooled to room temperature, assuming two types of unit cells:  √3 × √3R30° and 2 × 2. The results of the simulations showed that BZM formed a nearly perfect herringbone structure, while the apparent herringbone type structure of BT was somewhat disordered in the √3 × √3R30° unit cell. For the 2 × 2 unit cell with larger area per molecule, both monolayers did not form well-ordered structures, but the BZM showed some local ordering with herringbone structure. In both cases, the molecules of BZM are found to be nearly vertical to the surface, while those of BT are tilted from the surface normal. All these theoretical results are consistent with recent experimental findings. The role of a flexible methylene unit near the sulfur headgroup in discriminating stable packing structures of the self-assembled monolayers is discussed.

MicroRNAs (miRNAs) constitute an important class of regulators that are involved in various cellular and disease processes. However, the functional significance of each miRNA is mostly unknown due to the difficulty in identifying target genes and the lack of genome-wide expression data combining miRNAs, mRNAs and proteins. We introduce a novel database, miRGator, that integrates the target prediction, functional analysis, gene expression data and genome annotation. MiRNA function is inferred from the list of target genes predicted by miRanda, PicTar and TargetScanS programs. Statistical enrichment test of target genes in each term is performed for gene ontology, pathway and disease annotations. Associated terms may provide valuable insights for the function of each miRNA. For the expression analysis, miRGator integrates public expression data of miRNA with those of mRNA and protein. Expression correlation between miRNA and target mRNA/proteins is evaluated and their expression patterns can be readily compared. Our web implementation supports diverse query types including miRNA name, gene symbol, gene ontology, pathway and disease terms. Interfaces for exploring common targets or regulatory miRNAs and for profiling compendium expression data have been developed as well. Currently, miRGator, available at: http://genome.ewha.ac.kr/miRGator/, supports the human and mouse genomes.

The findings in this initial experience suggest that stent-graft insertion may be a safe and effective alternative to surgical treatment of aortic and arterial aneurysms in patients with Behçet disease.

We propose an effective scheme for fast conformational searches by combining the replica exchange method (REM) with the generalized effect potential concept. The present method introduces the "q" value from the effective potential as a coupling parameter. It is found that the new method not only requires a much smaller number of replicas than the conventional REM, but also makes it possible to perform effective conformational sampling of complex systems with correct distributions maintained. The advantage of the present method has been demonstrated with in vacuo alanine dipeptide using a molecular dynamics simulation.