Furthering the understanding of silicate-substitution in α-tricalcium phosphate : an X-ray diffraction, X-ray fluorescence and solid-state nuclear magnetic resonance study

High-purity (SupT) and reagent-grade (ST), stoichiometric and silicate-containing α-tricalcium phosphate (α-TCP: ST0/SupT0 and Si-TCP x = 0.10: ST10/SupT10) were prepared by solid-state reaction based on the substitution mechanism Ca3(PO4)(2-x)(SiO4)x. Samples were determined to be phase pure by X-ray diffraction (XRD), and Rietveld analysis performed on the XRD data confirmed inclusion of Si in the α-TCP structure as determined by increases in unit cell parameters; particularly marked increases in the b-axis and β-angle were observed. X-ray fluorescence (XRF) confirmed the presence of expected levels of Si in Si-TCP compositions as well as significant levels of impurities (Mg, Al and Fe) present in all ST samples; SupT samples showed both expected levels of Si and a high degree of purity. Phosphorus (31P) magic-angle-spinning solid-state nuclear magnetic resonance (MAS NMR) measurements revealed that the high-purity reagents used in the synthesis of SupT0 can resolve the 12 expected peaks in the 31P spectrum of α-TCP compared to the low-purity ST0 that showed significant spectral line broadening; line broadening was also observed with the inclusion of Si which is indicative of induced structural disorder. Silicon (29Si) MAS NMR was also performed on both Si-TCP samples which revealed Q0 species of Si with additional Si Q1/Q2 species that may indicate a potential charge-balancing mechanism involving the inclusion of disilicate groups; additional Q4 Si species were also observed, but only for ST10. Heating and cooling rates were briefly investigated by 31P MAS NMR which showed no significant line broadening other than that associated with the emergence of β-TCP which was only realised with the reagent-grade sample ST0. This study provides an insight into the structural effects of Si-substitution in α-TCP and could provide a basis for understanding how substitution affects the physicochemical properties of the material

Evolutionary relationships among barley and <i>Arabidopsis</i> core circadian clock and clock-associated genes

The circadian clock regulates a multitude of plant developmental and metabolic processes. In crop species, it contributes significantly to plant performance and productivity and to the adaptation and geographical range over which crops can be grown. To understand the clock in barley and how it relates to the components in the Arabidopsis thaliana clock, we have performed a systematic analysis of core circadian clock and clock-associated genes in barley, Arabidopsis and another eight species including tomato, potato, a range of monocotyledonous species and the moss, Physcomitrella patens. We have identified orthologues and paralogues of Arabidopsis genes which are conserved in all species, monocot/dicot differences, species-specific differences and variation in gene copy number (e.g. gene duplications among the various species). We propose that the common ancestor of barley and Arabidopsis had two-thirds of the key clock components identified in Arabidopsis prior to the separation of the monocot/dicot groups. After this separation, multiple independent gene duplication events took place in both monocot and dicot ancestors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00239-015-9665-0) contains supplementary material, which is available to authorized users

Identification of Genes Affecting the Toxicity of Anti-Cancer Drug Bortezomib by Genome-Wide Screening in S. pombe

Bortezomib/PS-341/Velcade, a proteasome inhibitor, is widely used to treat multiple myeloma. While several mechanisms of the cytotoxicity of the drug were proposed, the actual mechanism remains elusive. We aimed to identify genes affecting the cytotoxicity of Bortezomib in the fission yeast S.pombe as the drug inhibits this organism's cell division cycle like proteasome mutants. Among the 2815 genes screened (covering 56% of total ORFs), 19 genes, whose deletions induce strong synthetic lethality with Bortezomib, were identified. The products of the 19 genes included four ubiquitin enzymes and one nuclear proteasome factor, and 13 of them are conserved in humans. Our results will provide useful information for understanding the actions of Bortezomib within cells

NMNAT1 Mutations Cause Leber Congenital Amaurosis

Leber congenital amaurosis (LCA) is an infantile-onset form of inherited retinal degeneration characterized by severe vision loss. Two-thirds of LCA cases are caused by mutations in 17 known disease genes (RetNet Retinal Information Network). Using exome sequencing, we identified a homozygous missense mutation (c.25G>A, p.Val9Met) in NMNAT1 as likely disease-causing in two siblings of a consanguineous Pakistani kindred affected by LCA. This mutation segregated with disease in their kindred, including in three other children with LCA. NMNAT1 resides in the previously identified LCA9 locus and encodes the nuclear isoform of nicotinamide mononucleotide adenylyltransferase, a rate-limiting enzyme in nicotinamide adenine dinucleotide $(NAD^+)$ biosynthesis. Functional studies showed the p.Val9Met mutation decreased NMNAT1 enzyme activity. Sequencing NMNAT1 in 284 unrelated LCA families identified 14 rare mutations in 13 additional affected individuals. These results are the first to link an NMNAT isoform to disease and indicate that NMNAT1 mutations cause LCA

Mudanças nos compostos bioativos e atividade antioxidante de pimentas da região amazônica.

A Embrapa Amazônia Oriental possui um Banco Ativo de Pimenteira com diferentes genótipos do gênero Capsicum, os quais ainda não foram analisados, quanto às suas características funcionais e capacidade antioxidante. Este estudo objetivou determinar os teores de ácido ascórbico, compostos fenólicos, carotenoides totais e a atividade antioxidante total, em frutos imaturos e maduros de genótipos de pimentas Capsicum spp. As concentrações de vitamina C (100,76-361,65 mg 100 g-1 nos frutos imaturos e 36,70-157,76 mg 100 g-1 nos maduros) decresceram com a maturação dos frutos. Carotenoides totais não foram detectados nos frutos imaturos, porém, nos frutos maduros, observaram-se valores de 73,80-1349,97 mg g-1, em função do genótipo. Os teores de compostos fenólicos aumentaram nos frutos maduros (147,40-718,64 mg GAE 100 g-1), para oito dos nove genótipos avaliados. Os frutos de pimenteira apresentaram significativa atividade antioxidante (55,02-92,03 mM trolox g-1 nos frutos imaturos e 39,60-113,08 mM trolox g- 1 nos maduros). Concluiu-se que o grau de maturação dos frutos influenciou nos teores de compostos bioativos dos genótipos estudados. Destacaram-se, como genótipos promissores com potencial para serem utilizados em programas de melhoramento genético, IAN-186301 e IAN-186324, pelos altos teores de carotenoides totais; IAN-186301, IAN-186311, IAN-186312 e IAN-186313, com relação às altas concentrações de ácido ascórbico; IAN-186304 e IAN-186311, pelos altos teores de compostos fenólicos; e IAN-186311, para atividade antioxidante

EEG Markers in Emotionally Unstable Personality Disorder-A Possible Outcome Measure for Neurofeedback: A Narrative Review.

Objectives. There is growing evidence for the use of biofeedback (BF) in affective disorders, dissocial personality disorder, and in children with histories of abuse. Electroencephalogram (EEG) markers could be used as neurofeedback in emotionally unstable personality disorder (EUPD) management especially for those at high risk of suicide when emotionally aroused. This narrative review investigates the evidence for EEG markers in EUPD. Methods. PRISMA guidelines were used to conduct a narrative review. A structured search method was developed and implemented in collaboration with an information specialist. Studies were identified via 3 electronic database searches of MEDLINE, Embase, and PsycINFO. A predesigned inclusion/exclusion criterion was applied to selected papers. A thematic analysis approach with 5 criteria was used. Results. From an initial long list of 5250 papers, 229 studies were identified and screened, of which 44 met at least 3 of the predesigned inclusion criteria. No research to date investigates EEG-based neurofeedback in EUPD. A number of different EEG biomarkers are identified but there is poor consistency between studies. Conclusions. The findings heterogeneity may be due to the disorder complexity and the variable EEG related parameters studied. An alternative explanation may be that there are a number of different neuromarkers, which could be clustered together with clinical symptomatology, to give new subdomains. Quantitative EEGs in particular may be helpful to identify more specific abnormalities. EEG standardization of neurofeedback protocols based on specific EEG abnormalities detected may facilitate targeted use of neurofeedback as an intervention in EUPD

Functional Dissection of the Proton Pumping Modules of Mitochondrial Complex I

A catalytically active subcomplex of respiratory chain complex I lacks 14 of its 42 subunits yet retains half of its proton-pumping capacity, indicating that its membrane arm has two pump modules