Impaired Resting-State Functional Integrations within Default Mode Network of Generalized Tonic-Clonic Seizures Epilepsy

Generalized tonic-clonic seizures (GTCS) are characterized by unresponsiveness and convulsions, which cause complete loss of consciousness. Many recent studies have found that the ictal alterations in brain activity of the GTCS epilepsy patients are focally involved in some brain regions, including thalamus, upper brainstem, medial prefrontal cortex, posterior midbrain regions, and lateral parietal cortex. Notably, many of these affected brain regions are the same and overlap considerably with the components of the so-called default mode network (DMN). Here, we hypothesize that the brain activity of the DMN of the GTCS epilepsy patients are different from normal controls, even in the resting state. To test this hypothesis, we compared the DMN of the GTCS epilepsy patients and the controls using the resting state functional magnetic resonance imaging. Thirteen brain areas in the DMN were extracted, and a complete undirected weighted graph was used to model the DMN for each participant. When directly comparing the edges of the graph, we found significant decreased functional connectivities within the DMN of the GTCS epilepsy patients comparing to the controls. As for the nodes of the graph, we found that the degree of some brain areas within the DMN was significantly reduced in the GTCS epilepsy patients, including the anterior medial prefrontal cortex, the bilateral superior frontal cortex, and the posterior cingulate cortex. Then we investigated into possible mechanisms of how GTCS epilepsy could cause the reduction of the functional integrations of DMN. We suggested the damaged functional integrations of the DMN in the GTCS epilepsy patients even during the resting state, which could help to understand the neural correlations of the impaired consciousness of GTCS epilepsy patients

Multivariate Analysis of Dopaminergic Gene Variants as Risk Factors of Heroin Dependence

BACKGROUND: Heroin dependence is a debilitating psychiatric disorder with complex inheritance. Since the dopaminergic system has a key role in rewarding mechanism of the brain, which is directly or indirectly targeted by most drugs of abuse, we focus on the effects and interactions among dopaminergic gene variants. OBJECTIVE: To study the potential association between allelic variants of dopamine D2 receptor (DRD2), ANKK1 (ankyrin repeat and kinase domain containing 1), dopamine D4 receptor (DRD4), catechol-O-methyl transferase (COMT) and dopamine transporter (SLC6A3) genes and heroin dependence in Hungarian patients. METHODS: 303 heroin dependent subjects and 555 healthy controls were genotyped for 7 single nucleotide polymorphisms (SNPs) rs4680 of the COMT gene; rs1079597 and rs1800498 of the DRD2 gene; rs1800497 of the ANKK1 gene; rs1800955, rs936462 and rs747302 of the DRD4 gene. Four variable number of tandem repeats (VNTRs) were also genotyped: 120 bp duplication and 48 bp VNTR in exon 3 of DRD4 and 40 bp VNTR and intron 8 VNTR of SLC6A3. We also perform a multivariate analysis of associations using Bayesian networks in Bayesian multilevel analysis (BN-BMLA). FINDINGS AND CONCLUSIONS: In single marker analysis the TaqIA (rs1800497) and TaqIB (rs1079597) variants were associated with heroin dependence. Moreover, -521 C/T SNP (rs1800955) of the DRD4 gene showed nominal association with a possible protective effect of the C allele. After applying the Bonferroni correction TaqIB was still significant suggesting that the minor (A) allele of the TaqIB SNP is a risk component in the genetic background of heroin dependence. The findings of the additional multiple marker analysis are consistent with the results of the single marker analysis, but this method was able to reveal an indirect effect of a promoter polymorphism (rs936462) of the DRD4 gene and this effect is mediated through the -521 C/T (rs1800955) polymorphism in the promoter

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

NUCLEAR FACTOR Y, Subunit C (NF-YC) Transcription Factors Are Positive Regulators of Photomorphogenesis in Arabidopsis thaliana

We thank Dr. Ben Smith (University of Oklahoma) for assistance with FLIM-FRET measurements and Dr. Min Ni (University of Minnesota) for critical reading of the manuscript. The cop1-4 mutant allele and cop1-4 co-9 cross were kindly provided by George Coupland (Max Planck Institute).Author Summary Light perception is critically important for the fitness of plants in both natural and agricultural settings. Plants not only use light for photosynthesis, but also as a cue for proper development. As a seedling emerges from soil it must determine the light environment and adopt an appropriate growth habit. When blue and red wavelengths are the dominant sources of light, plants will undergo photomorphogenesis. Photomorphogenesis describes a number of developmental responses initiated by light in a seedling, and includes shortened stems and establishing the ability to photosynthesize. The genes regulating photomorphogenesis have been studied extensively, but a complete picture remains elusive. Here we describe the finding that NUCLEAR FACTOR-Y (NF-Y) genes are positive regulators of photomorphogenesis—i.e., in plants where NF-Y genes are mutated, they display some characteristics of dark grown plants, even though they are in the light. Our data suggests that the roles of NF-Y genes in light perception do not fit in easily with those of other described pathways. Thus, studying these genes promises to help develop a more complete picture of how light drives plant development.Yeshttp://www.plosgenetics.org/static/editorial#pee

Conducting polymer nanocomposite-based supercapacitors

The use of nanocomposites of electronically-conducting polymers for supercapacitors has increased significantly over the past years, due to their high capacitances and abilities to withstand many charge-discharge cycles. We have recently been investigating the use of nanocomposites of electronically-conducting polymers containing conducting and non-conducting nanomaterials such as carbon nanotubes and cellulose nanocrystals, for use in supercapacitors. In this contribution, we provide a summary of some of the key issues in this area of research. This discussion includes some history, fundamental concepts, the physical and chemical processes involved, and the challenges that these nanocomposite materials must overcome in order to become technologically viable. Due to space limitations, this is not a complete review of all the work that has been done in this field and we have focused on common themes that appear in the published work. Our aim is that this chapter will help readers to understand the advantages and challenges involved in the use of these materials in supercapacitors and to identify areas for further development

Preparation of novel side-chain pseudopolyrotaxanes consisting of cucurbituril[6] and polyamine salts

Pseudorotaxane monomer (VBCB) containing cucurbitutil[6] (CB[6]) and N-1-(4-vinylbenzyl)-1,4-diaminobutane dihydrochloride (VBDADC) is obtained by self-assembly of cucurbituril[6] with VBDADC in water and then polymerized using potassium persulfate (KPS) as initiator to give novel water-soluble side-chain cucurbituril [6]-based pseudopolyrotaxane (PVBCB). The chemical structures of PVBCB, VBCB and VBDADC are confirmed by H-1 NMR, C-13 NMR spectra and elemental analysis. In VBCB, CB[6] is localized aliphatic group of the side chain and the molar ratio of CB [6] to VBDAC is 1:1.X113sciescopu