Localizing confined epileptic foci in patients with an unclear focus or presumed multifocality using a component-based EEG-fMRI method

Precise localization of epileptic foci is an unavoidable prerequisite in epilepsy surgery. Simultaneous EEG-fMRI recording has recently created new horizons to locate foci in patients with epilepsy and, in comparison with single-modality methods, has yielded more promising results although it is still subject to limitations such as lack of access to information between interictal events. This study assesses its potential added value in the presurgical evaluation of patients with complex source localization. Adult candidates considered ineligible for surgery on account of an unclear focus and/or presumed multifocality on the basis of EEG underwent EEG-fMRI. Adopting a component-based approach, this study attempts to identify the neural behavior of the epileptic generators and detect the components-of-interest which will later be used as input in the GLM model, substituting the classical linear regressor. Twenty-eight sets interictal epileptiform discharges (IED) from nine patients were analyzed. In eight patients, at least one BOLD response was significant, positive and topographically related to the IEDs. These patients were rejected for surgery because of an unclear focus in four, presumed multifocality in three, and a combination of the two conditions in two. Component-based EEG-fMRI improved localization in five out of six patients with unclear foci. In patients with presumed multifocality, component-based EEG-fMRI advocated one of the foci in five patients and confirmed multifocality in one of the patients. In seven patients, component-based EEG-fMRI opened new prospects for surgery and in two of these patients, intracranial EEG supported the EEG-fMRI results. In these complex cases, component-based EEG-fMRI either improved source localization or corroborated a negative decision regarding surgical candidacy. As supported by the statistical findings, the developed EEG-fMRI method leads to a more realistic estimation of localization compared to the conventional EEG-fMRI approach, making it a tool of high value in pre-surgical evaluation of patients with refractory epilepsy. To ensure proper implementation, we have included guidelines for the application of component-based EEG-fMRI in clinical practice.     

Cell-extracellular matrix interactions regulate neural differentiation of human embryonic stem cells

Background  

Interactions of cells with the extracellular matrix (ECM) are critical for the establishment and maintenance of stem cell self-renewal and differentiation. However, the ECM is a complex mixture of matrix molecules; little is known about the role of ECM components in human embryonic stem cell (hESC) differentiation into neural progenitors and neurons.     

Concordant Time-Dependent Patterns of Activities and Enzyme Protein Amounts of V-PPase and V-ATPase in induced (Flowering and CAM or Tumour) and Non-Induced Plant Tissues*

There are two H⁺-pumping enzymes at the tonoplast membrane of plant vacuoles, the V-ATPase and the V-PPase. One attempt to explain the enigma of “two H⁺ pumps, one membrane” was the suggestion that the V-PPase has special functions in young developing and growing tissues in utilization of pyrophosphate produced in particularly active metabolism and in pumping of K⁺ for vacuolization. This should lead to reciprocal expression of both enzymes with time during development. Here we used stimulation of Kalanchoë blossfeldiana Poellnitz cv. Tom Thumb plants by short-day treatments to induce crassulacean acid metabolism and flowering and of Ricinus communis L. stem tissue by infection with Agrobacterium tumefaciens strain C58 to induce vigorous growth of tumours, and we compared these stimulated tissues with leaves of non-stimulated long-day controls and non-infected stem tissue, respectively. Activities and protein levels of both enzymes increased (K. blossfeldiana) or remained high (R. communis) in the stimulated tissues and decreased in the non-stimulated tissues with time. Time-dependent patterns of the two enzymes were concordant in all of the four cases and not inverse, i.e. two plants with two different conditions each, leading to very different developmental situations.     

Population genetics of the peoples of Iran I. Genetic polymorphisms of blood groups,serum proteins and red cell enzymes

Genetic polymorphisms of six blood groups and seven biochemical genetic markers were investigated in six Iranian populations (Turks, Kurds, Lurs, Zabolis, Baluchis and Zoroastrians). Eight of the genetic systems (ABO, MNSs, Kidd, C3, AP, AK, PGM1 and EsD) showed conclusive heterogeneity among these populations. Comparison of gene frequencies with the few available samples of Iranian populations demonstrated an intra-ethnic and extensive overall genetic diversity in the Iranian plateau. A gradient of C3*F gene was also discernible within the geographical region of Iran which may reflect the relics of the historical movements of different racial groups in this region. The present genetic variation may reflect the differences in the structure of these populations, the analysis of which is further attempted in the accompanying paper.     

Nanoparticles in cancer immunotherapies: An innovative strategy

Cancer has been one of the most significant causes of mortality, worldwide. Cancer immunotherapy has recently emerged as a competent, cancer-fighting clinical strategy. Nevertheless, due to the difficulty of such treatments, costs, and off-target adverse effects, the implementation of cancer immunotherapy described by the antigen-presenting cell (APC) vaccine and chimeric antigen receptor T cell therapy ex vivo in large clinical trials have been limited. Nowadays, the nanoparticles theranostic system as a promising target-based modality provides new opportunities to improve cancer immunotherapy difficulties and reduce their adverse effects. Meanwhile, the appropriate engineering of nanoparticles taking into consideration nanoparticle characteristics, such as, size, shape, and surface features, as well as the use of these physicochemical properties for suitable biological interactions, provides new possibilities for the application of nanoparticles in cancer immunotherapy. In this review article, we focus on the latest state-of-the-art nanoparticle-based antigen/adjuvant delivery vehicle strategies to professional APCs and engineering specific T lymphocyte required for improving the efficiency of tumor-specific immunotherapy.     

Reversible redox control of plant vacuolar H+–ATPase activity is related to disulfide bridge formation in subunit E as well as subunit A

The plant vacuolar proton pump can be subjected to reversible redox regulation in vitro. The redox-dependent activity change involves disulfide bridge formation not only in Vatp A, as reported for bovine V-ATPase, but also in the stalk subunit Vatp E. Microsomal membranes isolated from barley leaves were analysed for their activity of bafilomycin-sensitive ATP hydrolysis and proton pumping using quinacrine fluorescence quenching in vesicle preparations. ATP hydrolysis and proton pumping activity were inhibited by H2O2. H2O2-deactivated ATPase was reactivated by cysteine and glutathione. The glutathione concentration needed for half maximal reactivation was 1 mmol l-1. The activity loss was accompanied by shifts in electrophoretic mobility of Vatp A and E which were reversed upon reductive reactivation. The redox-dependent shift was also seen with recombinant Vatp E, and was absent following site-directed mutagenesis of either of the two cys residues conserved throughout all plant Vatp E sequences. V-ATPase was also inhibited by oxidized thioredoxin. These results support the hypothesis that tuning of vacuolar ATPase activity can be mediated by redox control depending on the metabolic requirements.     

Serum proteins and erythrocyte enzymes of populations in Iran

The genetic polymorphisms of nine biochemical genetic markers were investigated in four populations (Turks, Kurds, Tehranis and Kermanis) living in the north-east and south-east regions of Iran. Only one of the nine loci studied (acid phosphatase) showed significant gene frequency differences and for the C3 system the F allele frequencies in these populations were the lowest ever reported from Iran.