Search results for " IS"
showing 10 items of 5661 documents
Prognostic value of methylator phenotype in stage III colon cancer treated with oxaliplatin-based adjuvant chemotherapy
2017
Abstract Purpose: There are conflicting results concerning the prognostic value of the CpG island methylator phenotype (CIMP) in patients with nonmetastatic colon cancer. We studied this phenotype in stage III colon cancer characterized for mismatch repair (MMR), RAS, and BRAF status, and treated with adjuvant FOLFOX-based regimen. Experimental Design: Tumor samples of 1,907 patients enrolled in the PETACC-8 adjuvant phase III trial were analyzed. The method used was methylation-specific PCR, where CIMP+ status was defined by methylation of at least 3 of 5 following genes: IGF2, CACNA1G, NEUROG1, SOCS1, and RUNX3. Association between CIMP status and overall survival (OS), disease-free survi…
Lack of R-Ras Leads to Increased Vascular Permeability in Ischemic Retinopathy
2016
PURPOSE. The role of R-Ras in retinal angiogenesis and vascular permeability was evaluated in an oxygen-induced retinopathy (OIR) model using R-Ras knockout (KO) mice and in human diabetic neovascular membranes. METHODS. Mice deficient for R-Ras and their wild-type (WT) littermates were subjected to 75% oxygen from postnatal day 7 (P7) to P12 and then returned to room air. At P17 retinal vascularization was examined from whole mounts, and retinal vascular permeability was studied using Miles assay. Real-time RT-PCR, Western blotting, and immunohistochemistry were used to assess the expression of R-Ras in retina during development or in the OIR model. The degree of pericyte coverage and vasc…
Early silent microstructural degeneration and atrophy of the thalamocortical network in multiple sclerosis
2016
Recent studies on patients with clinically isolated syndrome (CIS) and multiple sclerosis (MS) demonstrated thalamic atrophy. Here we addressed the following question: Is early thalamic atrophy in patients with CIS and relapsing-remitting MS (RRMS) mainly a direct consequence of white matter (WM) lesions-as frequently claimed-or is the atrophy stronger correlated to "silent" (nonlesional) microstructural thalamic alterations? One-hundred and ten patients with RRMS, 12 with CIS, and 30 healthy controls were admitted to 3 T magnetic resonance imaging. Fractional anisotropy (FA) was computed from diffusion tensor imaging (DTI) to assess thalamic and WM microstructure. The relative thalamic vol…
Devices containing allyl isothiocyanate against the growth of spoilage and mycotoxigenic fungi in mozzarella cheese
2018
Filter paper and stickers containing allyl isothiocyanate (AIT), as well as pouches containing mustard meal and water for intrinsic production of AIT, were tested against aflatoxigenic strains of Penicillium digitatum CECT 2954 and Aspergillus parasiticus CECT 2681 in sliced mozzarella. Slices were inoculated with either fungus, packaged in plastic bags or plastic trays with one antimicrobial device (2–16 µL/L of AIT). Control groups presented visual growth of P. digitatum after 19.0 ± 1.5 d in bags and 26.1 ± 2.1 d in trays. A. parasiticus was visually detectable after 41.4 ± 1.7 d and 28.4 ± 1.5 d in trays and bags, respectively. AIT‐treated samples did not present visual fungal growth fo…
Linoleic acid: Is this the key that unlocks the quantum brain? Insights linking broken symmetries in molecular biology, mood disorders and personalis…
2017
Abstract In this paper we present a mechanistic model that integrates subneuronal structures, namely ion channels, membrane fatty acids, lipid rafts, G proteins and the cytoskeleton in a dynamic system that is finely tuned in a healthy brain. We also argue that subtle changes in the composition of the membrane’s fatty acids may lead to down-stream effects causing dysregulation of the membrane, cytoskeleton and their interface. Such exquisite sensitivity to minor changes is known to occur in physical systems undergoing phase transitions, the simplest and most studied of them is the so-called Ising model, which exhibits a phase transition at a finite temperature between an ordered and disorde…
Femtosecond structural dynamics drives the trans/cis isomerization in photoactive yellow protein
2016
Many biological processes depend on detecting and responding to light. The response is often mediated by a structural change in a protein that begins when absorption of a photon causes isomerization of a chromophore bound to the protein. Pande et al. used x-ray pulses emitted by a free electron laser source to conduct time-resolved serial femtosecond crystallography in the time range of 100 fs to 3 ms. This allowed for the real-time tracking of the trans-cis isomerization of the chromophore in photoactive yellow protein and the associated structural changes in the protein.Science, this issue p. 725A variety of organisms have evolved mechanisms to detect and respond to light, in which the re…
DNA methylation links prenatal smoking exposure to later life health outcomes in offspring
2019
Background Maternal smoking during pregnancy is associated with adverse offspring health outcomes across their life course. We hypothesize that DNA methylation is a potential mediator of this relationship. Methods We examined the association of prenatal maternal smoking with offspring blood DNA methylation in 2821 individuals (age 16 to 48 years) from five prospective birth cohort studies and perform Mendelian randomization and mediation analyses to assess whether methylation markers have causal effects on disease outcomes in the offspring. Results We identify 69 differentially methylated CpGs in 36 genomic regions (P value < 1 × 10−7) associated with exposure to maternal smoking in adolesc…
KnotGenome: a server to analyze entanglements of chromosomes.
2018
Abstract The KnotGenome server enables the topological analysis of chromosome model data using three-dimensional coordinate files of chromosomes as input. In particular, it detects prime and composite knots in single chromosomes, and links between chromosomes. The knotting complexity of the chromosome is presented in the form of a matrix diagram that reveals the knot type of the entire polynucleotide chain and of each of its subchains. Links are determined by means of the Gaussian linking integral and the HOMFLY-PT polynomial. Entangled chromosomes are presented graphically in an intuitive way. It is also possible to relax structure with short molecular dynamics runs before the analysis. Kn…
Quantitative analysis of the impact of a human pathogenic mutation on the CCT5 chaperonin subunit using a proxy archaeal ortholog
2017
The human chaperonin complex is a ~ 1 MDa nanomachine composed of two octameric rings formed from eight similar but non-identical subunits called CCT. Here, we are elucidating the mechanism of a heritable CCT5 subunit mutation that causes profound neuropathy in humans. In previous work, we introduced an equivalent mutation in an archaeal chaperonin that assembles into two octameric rings like in humans but in which all subunits are identical. We reported that the hexadecamer formed by the mutant subunit is unstable with impaired chaperoning functions. This study quantifies the loss of structural stability in the hexadecamer due to the pathogenic mutation, using differential scanning calorim…
MycoKey Round Table Discussions of Future Directions in Research on Chemical Detection Methods, Genetics and Biodiversity of Mycotoxins
2018
MycoKey, an EU-funded Horizon 2020 project, includes a series of “Roundtable Discussions” to gather information on trending research areas in the field of mycotoxicology. This paper includes summaries of the Roundtable Discussions on Chemical Detection and Monitoring of mycotoxins and on the role of genetics and biodiversity in mycotoxin production. Discussions were managed by using the nominal group discussion technique, which generates numerous ideas and provides a ranking for those identified as the most important. Four questions were posed for each research area, as well as two questions that were common to both discussions. Test kits, usually antibody based, were one major focus of the…