A 'molten globule'-like unfolding intermediate of a four domain protein, the Fc fragment of the IgG molecule

The Fc fragment of human IgG1 can be trapped in a stable intermediate state during thermal denaturation. In this conformation the molecule is compact with a native-like secondary structure, however, the tertiary structure is perturbed as revealed by intrinsic fluorescence measurements, the near-UV CD spectra and by mapping of antigenic sites with monoclonal antibodies. Similar phenomena were recently described for a few globular proteins of small size, and termed 'the molten globule' state. Our observation is a unique example of this phenomenon for a four domain protein.     

The Candidate Oncogene CYP24A1: A Potential Biomarker for Colorectal Tumorigenesis

The main autocrine/paracrine role of the active metabolite of vitamin D₃, 1α,25-dihydroxyvitamin D₃ (1,25-D₃), is inhibition of cell growth and induction of cell differentiation and/or apoptosis. Synthesis and degradation of the secosteroid occurs not only in the kidney but also in normal tissue or malignant extrarenal tissues such as the colon. Because 25-hydroxyvitamin D₃ 24-hydroxylase (CYP24A1) is considered to be the main enzyme determining the biological half-life of 1,25-D₃, we have examined expression of the CYP24A1 mRNA (by real-time RT-PCR) and protein (by immunohistochemistry) in normal human colon mucosa, colorectal adenomas, and adenocarcinomas in 111 patients. Although 76% of the normal and benign colonic tissue was either completely devoid of or expressed very low levels of CYP24A1, in the majority of the adenocarcinomas (69%), the enzyme was present at high concentrations. A parallel increased expression of the proliferation marker Ki-67 in the same samples suggests that overexpression of CYP24A1 reduced local 1,25-D₃ availability, decreasing its antiproliferative effect. (J Histochem Cytochem 58:277–285, 2010)     

Molecular mechanism of RNA silencing suppression mediated by p19 protein of tombusviruses

RNA silencing is an evolutionarily conserved surveillance system that occurs in a broad range of eukaryotic organisms. In plants, RNA silencing acts as an antiviral system; thus, successful virus infection requires suppression of gene silencing. A number of viral suppressors have been identified so far; however, the molecular bases of silencing suppression are still poorly understood. Here we show that p19 of Cymbidium ringspot virus (CymRSV) inhibits RNA silencing via its small RNA-binding activity in vivo. Small RNAs bound by p19 in planta are bona fide double-stranded siRNAs and they are silencing competent in the in vitro RNA-silencing system. p19 also suppresses RNA silencing in the heterologous Drosophila in vitro system by preventing siRNA incorporation into RISC. During CymRSV infection, p19 markedly diminishes the amount of free siRNA in cells by forming p19-siRNA complexes, thus making siRNAs inaccessible for effector complexes of RNA-silencing machinery. Furthermore, the obtained results also suggest that the p19-mediated sequestration of siRNAs in virus-infected cells blocks the spread of the mobile, systemic signal of RNA silencing.     

Efficient microalgae feed production for fish hatcheries using an annular column photobioreactor characterized by a short light path and central LED illumination

Journal of Applied Phycology - In this study, we aimed to set up and test two models of annular-column photobioreactors (AC-PBR 1 and AC-PBR 2) in order to produce microalgae for fish hatcheries....     

Empirical derivation of the reference region for computing diagnostic sensitive ¹⁸fluorodeoxyglucose ratios in Alzheimer's disease based on the ADNI sample

Careful selection of the reference region for non-quantitative positron emission tomography (PET) analyses is critically important for Region of Interest (ROI) data analyses. We introduce an empirical method of deriving the most suitable reference region for computing neurodegeneration sensitive (18)fluorodeoxyglucose (FDG) PET ratios based on the dataset collected by the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. Candidate reference regions are selected based on a heat map of the difference in coefficients of variation (COVs) of FDG ratios over time for each of the Automatic Anatomical Labeling (AAL) atlas regions normalized by all other AAL regions. Visual inspection of the heat map suggests that the portion of the cerebellum and vermis superior to the horizontal fissure is the most sensitive reference region. Analyses of FDG ratio data show increases in significance on the order of ten-fold when using the superior portion of the cerebellum as compared with the traditionally used full cerebellum. The approach to reference region selection in this paper can be generalized to other radiopharmaceuticals and radioligands as well as to other disorders where brain changes over time are hypothesized and longitudinal data is available. Based on the empirical evidence presented in this study, we demonstrate the usefulness of the COV heat map method and conclude that intensity normalization based on the superior portion of the cerebellum may be most sensitive to measuring change when performing longitudinal analyses of FDG-PET ratios as well as group comparisons in Alzheimer's disease. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.     

Neuronal oscillations and multisensory interaction in primary auditory cortex

Recent anatomical, physiological, and neuroimaging findings indicate multisensory convergence at early, putatively unisensory stages of cortical processing. The objective of this study was to confirm somatosensory-auditory interaction in A1 and to define both its physiological mechanisms and its consequences for auditory information processing. Laminar current source density and multiunit activity sampled during multielectrode penetrations of primary auditory area A1 in awake macaques revealed clear somatosensory-auditory interactions, with a novel mechanism: somatosensory inputs appear to reset the phase of ongoing neuronal oscillations, so that accompanying auditory inputs arrive during an ideal, high-excitability phase, and produce amplified neuronal responses. In contrast, responses to auditory inputs arriving during the opposing low-excitability phase tend to be suppressed. Our findings underscore the instrumental role of neuronal oscillations in cortical operations. The timing and laminar profile of the multisensory interactions in A1 indicate that nonspecific thalamic systems may play a key role in the effect.     

Effect of co-substrate feeding on methane yield of anaerobic digestion of <Emphasis Type="Italic">Chlorella vulgaris</Emphasis>

Microalgal production has many advantages over the use of terrestrial plants; therefore, increases in the use of microalgae for energy production can be expected. Algal biomass can be processed anaerobically to methane; however, the unfavorable C/N ratio of the substrate may have an inhibitory effect. The impact of the application of used cooking oil, maize silage, and mill residue on anaerobic co-digestion of the microalgal Chlorella vulgaris was studied in semi-continuous, laboratory-scale digestion. During the full period of the trial involving anaerobic digestion of algae in the case of mono-digestion and co-digestion with used cooking oil, maize silage, and mill residue, the volumetric methane yields were 0.38?±?0.07, 1.56?±?0.26, 1.19?±?0.18, and 1.16?±?0.13 L L^?1, respectively. Trials were carried out to determine the long-term effect of the total solid (TS) content of substrates (co-digestion of C. vulgaris and used cooking oil at 3.8 and 7.2 % of TS, respectively). Both designs could be increased to 5.5 g VS L^?1 d^?1, but a higher TS% resulted in increased methane production and a longer period of decline in the methane yield due to washout. The sharp decrease in methane content at the end of 90 days was accompanied by a reorganization of the methanogenic archaeal community.