Clar's Theory, STM Images, and Geometry of Graphene Nanoribbons

We show that Clar's theory of the aromatic sextet is a simple and powerful tool to predict the stability, the \pi-electron distribution, the geometry, the electronic/magnetic structure of graphene nanoribbons with different hydrogen edge terminations. We use density functional theory to obtain the equilibrium atomic positions, simulated scanning tunneling microscopy (STM) images, edge energies, band gaps, and edge-induced strains of graphene ribbons that we analyze in terms of Clar formulas. Based on their Clar representation, we propose a classification scheme for graphene ribbons that groups configurations with similar bond length alternations, STM patterns, and Raman spectra. Our simulations show how STM images and Raman spectra can be used to identify the type of edge termination

Increased d-amino acid oxidase expression in the bilateral hippocampal CA4 of schizophrenic patients: a post-mortem study

An important risk gene in schizophrenia is d-amino acid oxidase (DAAO). To establish if expression of DAAO is altered in cortical, hippocampal or thalamic regions of schizophrenia patients, we measured gene expression of DAAO in a post-mortem study of elderly patients with schizophrenia and non-affected controls in both hemispheres differentiating between gray and white matter. We compared cerebral post-mortem samples (granular frontal cortex BA9, middle frontal cortex BA46, superior temporal cortex BA22, entorhinal cortex BA28, sensoric cortex BA1–3, hippocampus (CA4), mediodorsal nucleus of the thalamus) from 10 schizophrenia patients to 13 normal subjects investigating gene expression of DAAO in the gray and white matter of both hemispheres of the above-mentioned brain regions by in situ-hybridization. We found increased expression of DAAO-mRNA in the hippocampal CA4 of schizophrenic patients. Compared to the control group, both hemispheres of the hippocampus of schizophrenic patients showed an increased expression of 46% (right, P = 0.013) and 54% (left, P = 0.019), respectively. None of the other regions examined showed statistically significant differences in DAAO expression. This post-mortem study demonstrated increased gene expression of DAAO in the left and right hippocampus of schizophrenia patients. This increased expression could be responsible for a decrease in local d-serine levels leading to a NMDA-receptor hypofunction that is hypothesized to play a major role in the pathophysiology of schizophrenia. However, our study group was small and results should be verified using larger samples

Photoinduced Structural Phase Transitions in Polyacene

There exist two types of structural instability in polyacene: double bonds in a cis pattern and those in a trans pattern. They are isoenergetic but spectroscopically distinct. We demonstrate optical characterization and manipulation of Peierls-distorted polyacene employing both correlated and uncorrelated Hamiltonians. We clarify the phase boundaries of the cis- and trans-distorted isomers, elucidate their optical-conductivity spectra, and then explore their photoresponses. There occurs a photoinduced transformation in the polyacene structure, but it is one-way switching: The trans configuration is well convertible into the cis one, whereas the reverse conversion is much less feasible. Even the weakest light irradiation can cause a transition of uncorrelated electrons, while correlated electrons have a transition threshold against light irradiation.Comment: 14 pages with 15 figures embedde

The ongoing pursuit of neuroprotective therapies in Parkinson disease

Many agents developed for neuroprotective treatment of Parkinson disease (PD) have shown great promise in the laboratory, but none have translated to positive results in patients with PD. Potential neuroprotective drugs, such as ubiquinone, creatine and PYM50028, have failed to show any clinical benefits in recent high-profile clinical trials. This 'failure to translate' is likely to be related primarily to our incomplete understanding of the pathogenic mechanisms underlying PD, and excessive reliance on data from toxin-based animal models to judge which agents should be selected for clinical trials. Restricted resources inevitably mean that difficult compromises must be made in terms of trial design, and reliable estimation of efficacy is further hampered by the absence of validated biomarkers of disease progression. Drug development in PD dementia has been mostly unsuccessful; however, emerging biochemical, genetic and pathological evidence suggests a link between tau and amyloid-β deposition and cognitive decline in PD, potentially opening up new possibilities for therapeutic intervention. This Review discusses the most important 'druggable' disease mechanisms in PD, as well as the most-promising drugs that are being evaluated for their potential efficiency in treatment of motor and cognitive impairments in PD

Mechanical Bonds and Topological Effects in Radical Dimer Stabilization

While mechanical bonding stabilizes tetrathiafulvalene (TTF) radical dimers, the question arises: what role does topology play in catenanes containing TTF units? Here, we report how topology, together with mechanical bonding, in isomeric [3]- and doubly interlocked [2]catenanes controls the formation of TTF radical dimers within their structural frameworks, including a ring-in-ring complex (formed between an organoplatinum square and a {2+2} macrocyclic polyether containing two 1,5-dioxynaphthalene (DNP) and two TTF units) that is topologically isomeric with the doubly interlocked [2]catenane. The separate TTF units in the two {1+1} macrocycles (each containing also one DNP unit) of the isomeric [3]catenane exhibit slightly different redox properties compared with those in the {2+2} macrocycle present in the [2]catenane, while comparison with its topological isomer reveals substantially different redox behavior. Although the stabilities of the mixed-valence (TTF2)^(•+) dimers are similar in the two catenanes, the radical cationic (TTF^(•+))_2 dimer in the [2]catenane occurs only fleetingly compared with its prominent existence in the [3]catenane, while both dimers are absent altogether in the ring-in-ring complex. The electrochemical behavior of these three radically configurable isomers demonstrates that a fundamental relationship exists between topology and redox properties

Fluorescence-Quenched Substrates for Live Cell Imaging of Human Glucocerebrosidase Activity

Deficiency of the lysosomal glycoside hydrolase glucocerebrosidase (GCase) leads to abnormal accumulation of glucosyl ceramide in lysosomes and the development of the lysosomal storage disease known as Gaucher’s disease. More recently, mutations in the GBA1 gene that encodes GCase have been uncovered as a major genetic risk factor for Parkinson’s disease (PD). Current therapeutic strategies to increase GCase activity in lysosomes involve enzyme replacement therapy (ERT) and molecular chaperone therapy. One challenge associated with developing and optimizing these therapies is the difficulty in determining levels of GCase activity present within the lysosomes of live cells. Indeed, visualizing the activity of endogenous levels of any glycoside hydrolases, including GCase, has proven problematic within live mammalian cells. Here we describe the successful modular design and synthesis of fluorescence-quenched substrates for GCase. The selection of a suitable fluorophore and quencher pair permits the generation of substrates that allow convenient time-dependent monitoring of endogenous GCase activity within cells as well as localization of activity within lysosomes. These efficiently quenched (∼99.9%) fluorescent substrates also permit assessment of GCase inhibition in live cells by either confocal microscopy or high content imaging. Such substrates should enable improved understanding of GCase in situ as well the optimization of small-molecule chaperones for this enzyme. These findings also suggest routes to generate fluorescence-quenched substrates for other mammalian glycoside hydrolases for use in live cell imaging

Morphological changes in electrochemically deposited poly(3,4-ethylenedioxythiophene) films during overoxidation

Electrochemical and morphological properties of thin poly(3,4-ethylenedioxy-thiophene) (PEDOT) films deposited on gold were investigated in aqueous sulfuric acid solutions. X-ray diffraction and electron microscopy were used for monitoring the morphological changes and structure evolution caused by overoxidation. The diffraction peaks of PEDOT became sharper and more intensive during the subsequent oxidation cycles. This indicates that besides the degradation of the PEDOT film, its crystallinity was gradually improved with increasing the number of oxidation cycles. These changes may result in the appearance of novel properties that may be advantageous for specific applications