A Typical Case Presentation with Spontaneous Visual Recovery in Patient Diagnosed with Leber Hereditary Optic Neuropathy Due to Rare Point Mutation in MT-ND4 Gene (m.11253T>C) and Literature Review

Leber hereditary optic neuropathy (LHON) is one of the most common inherited mitochondrial optic neuropathies, caused by mitochondrial DNA (mtDNA) mutations. Three most common mutations, namely m.11778G>A, m.14484T>G and m.3460G>A, account for the majority of LHON cases. These mutations lead to mitochondrial respiratory chain complex I damage. Typically, LHON presents at the 15–35 years of age with male predominance. LHON is associated with severe, subacute, painless bilateral vision loss and account for one of the most common causes of legal blindness in young individuals. Spontaneous visual acuity recovery is rare and has been reported in patients harbouring m.14484T>C mutation. Up to date LHON treatment is limited. Idebenone has been approved by European Medicines Agency (EMA) to treat LHON. However better understanding of disease mechanisms and ongoing treatment trials are promising and brings hope for patients. In this article we report on a patient diagnosed with LHON harbouring rare m.11253T>C mutation in MT-ND4 gene, who experienced spontaneous visual recovery. In addition, we summarise clinical presentation, diagnostic features, and treatment

Excitation Dynamics and Relaxation in a Molecular Heterodimer

The exciton dynamics in a molecular heterodimer is studied as a function of differences in excitation and reorganization energies, asymmetry in transition dipole moments and excited state lifetimes. The heterodimer is composed of two molecules modeled as two-level systems coupled by the resonance interaction. The system-bath coupling is taken into account as a modulating factor of the energy gap of the molecular excitation, while the relaxation to the ground state is treated phenomenologically. Comparison of the description of the excitation dynamics modeled using either the Redfield equations (secular and full forms) or the Hierarchical quantum master equation (HQME) is demonstrated and discussed. Possible role of the dimer as an excitation quenching center in photosynthesis self-regulation is discussed. It is concluded that the system-bath interaction rather than the excitonic effect determines the excitation quenching ability of such a dimer

Zafirlukast is a broad-spectrum thiol isomerase inhibitor that inhibits thrombosis without altering bleeding times

Background and purpose Multiple members of the thiol isomerase (TI) family of enzymes are present in, and released by platelets. Inhibition of these enzymes results in diminished platelet responses including aggregation, adhesion and thrombus formation. In recent years, the therapeutic potential of TI inhibition has been recognised and drug-development technologies used to identify selective small molecule inhibitors. To date, few pan-TI inhibitors have been characterised and the most studied, bacitracin is known to be nephrotoxic which prohibits its systemic therapeutic usage. Experimental approach We therefore sought to identify novel broad-spectrum inhibitors of these enzymes and test their effects in vivo. 3641 compounds were screened for inhibitory effects on the redox activity of ERp5, PDI, ERp57, ERp72 and thioredoxin (TRX) in an insulin turbidity assay. Of the lead compounds identified, zafirlukast (ZFL) was selected for further investigation. Key results When applied to platelets, ZFL diminished platelet responses in vitro. ZFL was antithrombotic in murine models of thrombosis but did not impair responses in a model of haemostasis. Since thiol isomerases are known to modulate adhesion receptor function, we explored the effects of ZFL on cell migration. This was inhibited independently of cysteinyl leukotriene receptor expression and was associated with modulation of cell-surface free thiol levels consistent with alterations in redox activity on the cell surface. Conclusion and implications We identify zafirlukast to be a novel, potent, broad-spectrum TI inhibitor, with wide ranging effects on platelet function, thrombosis and integrin-mediated cell migration. ZFL is antithrombotic but does not cause bleeding

Morphological segmentation analysis and texture-based support vector machines classification on mice liver fibrosis microscopic images

Background To reduce the intensity of the work of doctors, pre-classification work needs to be issued. In this paper, a novel and related liver microscopic image classification analysis method is proposed. Objective For quantitative analysis, segmentation is carried out to extract the quantitative information of special organisms in the image for further diagnosis, lesion localization, learning and treating anatomical abnormalities and computer-guided surgery. Methods in the current work, entropy based features of microscopic fibrosis mice’ liver images were analyzed using fuzzy c-cluster, k-means and watershed algorithms based on distance transformations and gradient. A morphological segmentation based on a local threshold was deployed to determine the fibrosis areas of images. Results the segmented target region using the proposed method achieved high effective microscopy fibrosis images segmenting of mice liver in terms of the running time, dice ratio and precision. The image classification experiments were conducted using Gray Level Co-occurrence Matrix (GLCM). The best classification model derived from the established characteristics was GLCM which performed the highest accuracy of classification using a developed Support Vector Machine (SVM). The training model using 11 features was found to be as accurate when only trained by 8 GLCMs. Conclusion The research illustrated the proposed method is a new feasible research approach for microscopy mice liver image segmentation and classification using intelligent image analysis techniques. It is also reported that the average computational time of the proposed approach was only 2.335 seconds, which outperformed other segmentation algorithms with 0.8125 dice ratio and 0.5253 precision

Carrier Tunneling from Charge Transfer States in Organic Photovoltaic Cells

Charge transfer (CT) states play a key role in the functioning of organic solar cells; however, understanding the mechanism by which CT states dissociate efficiently into free charges remain a conceptual challenge. Here, the electric field dependent dynamics of charge generation in planar cyanine/fullerene photovoltaic cells is probed over a wide temperature range using time-resolved Stark effect experiments, transient absorption, and photocurrent measurements. Results indicate that dissociation of thermalized CT states is the rate-limiting step for all temperatures. The dissociation rate strongly depends on the field, but is temperature independent. The results also suggest that the yield of generated charges is temperature independent. Model electrostatic calculations illustrate that specific orientations of the cyanine crystal relative to C60 create a repulsive potential for an electron near the interface that is largely due to the quadrupole moment of the unit cell. In combination with the electron-hole coulomb attraction and the electric field-induced barrier lowering, a high-energy potential barrier forms with a narrow width of a few nanometers. It is proposed that charge separation occurs via a field-dependent electron tunneling mechanism through that barrier, which is temperature independent. The results support a thus far overlooked pathway for CT state dissociation via carrier tunneling

Modeling of excitation dynamics in photosynthetic light-harvesting complexes: exact versus perturbative approaches

We compare various theoretical approaches that are frequently used for modeling the excitation dynamics in photosynthetic light-harvesting complexes. As an example, we calculate the dynamics in the major light-harvesting complex from higher plants using the standard Redfield theory, the coherent modified Redfield theory combined with the generalized Forster theory, and the scaled hierarchical equation of motion (HEOM). The modified Redfield and coherent modified Redfield theories predict unrealistically fast transfers between weakly coupled and isoenergetic sites due to the secular character of these approaches. This shortcoming can be excluded by the artificial breaking of exciton mixing between these sites and invoking a generalized Forster theory to calculate the transfers between them. A critical cutoff indicating which exciton couplings should be broken is dependent on the energy gap between the corresponding sites (and therefore can be different for different parts of the complex). An adequate determination of the strongly coupled compartments of the whole complex allows us to obtain a quantitatively correct description with the combined Redfield-Forster approach, resulting in kinetics not much different from the exact HEOM solution