Uncertainty analysis of the use of a retailer fidelity card scheme in the assessment of food additive intake

International audienceThe feasibility of using a retailer fidelity card scheme to estimate food additive intake has been investigated in an earlier study. Fidelity card survey information was combined with information provided by the retailer on levels of the food colour Sunset Yellow (E110) in the foods to estimate a daily exposure to the additive in the Swiss population. As with any dietary exposure method the fidelity card scheme is subject to uncertainties and in this paper the impact of uncertainties associated with input variables including amounts of food purchased, levels of E110 in food, proportion of food purchased at retailer, rate of fidelity card usage, proportion of foods consumed outside of home and bodyweights and with systematic uncertainties has been assessed using a qualitative, deterministic and probabilistic approach. An analysis of the sensitivity of the results to each of the probabilistic inputs was also undertaken. The analysis was able to identify the key factors responsible for uncertainty within the model and demonstrate how the application of some simple probabilistic approaches can be used to quantitatively assess uncertainty

Guillain-Barré syndrome : causes, immunopathogenic mechanisms and treatment

Introduction: Guillain-Barr\ue9 syndrome is a rare disease representing the most frequent cause of acute flaccid symmetrical weakness of the limbs and areflexia usually reaching its peak within a month. The etiology and pathogenesis remain largely enigmatic and the syndrome results in death or severe disability in 9\u201317% of cases despite immunotherapy. Areas covered: In terms of etiology, Guillain-Barr\ue9 syndrome is linked to Campylobacter infection but less than 0.1% of infections result in the syndrome. In terms of pathogenesis, activated macrophages and T cells and serum antibodies against gangliosides are observed but their significance is unclear. Expert commentary: Guillain-Barr\ue9 syndrome is a heterogeneous condition with numerous subtypes and recent data point towards the role of ganglioside epitopes by immunohistochemical methods. Ultimately, the syndrome results from a permissive genetic background on which environmental factors, including infections, vaccination and the influence of aging, lead to disease

Analysis of Poly(ADP-Ribose) Polymerases in Arabidopsis Telomere Biology

Maintaining the length of the telomere tract at chromosome ends is a complex process vital to normal cell division. Telomere length is controlled through the action of telomerase as well as a cadre of telomere-associated proteins that facilitate replication of the chromosome end and protect it from eliciting a DNA damage response. In vertebrates, multiple poly(ADP-ribose) polymerases (PARPs) have been implicated in the regulation of telomere length, telomerase activity and chromosome end protection. Here we investigate the role of PARPs in plant telomere biology. We analyzed Arabidopsis thaliana mutants null for PARP1 and PARP2 as well as plants treated with the PARP competitive inhibitor 3-AB. Plants deficient in PARP were hypersensitive to genotoxic stress, and expression of PARP1 and PARP2 mRNA was elevated in response to MMS or zeocin treatment or by the loss of telomerase. Additionally, PARP1 mRNA was induced in parp2 mutants, and conversely, PARP2 mRNA was induced in parp1 mutants. PARP3 mRNA, by contrast, was elevated in both parp1 and parp2 mutants, but not in seedlings treated with 3-AB or zeocin. PARP mutants and 3-AB treated plants displayed robust telomerase activity, no significant changes in telomere length, and no end-to-end chromosome fusions. Although there remains a possibility that PARPs play a role in Arabidopsis telomere biology, these findings argue that the contribution is a minor one

Self-trapping of excitons, violation of condon approximation, and efficient fluorescence in conjugated cycloparaphenylenes

Cycloparaphenylenes, the simplest structural unit of armchair carbon nanotubes, have unique optoelectronic properties counterintuitive in the class of conjugated organic materials. Our time-dependent density functional theory study and excited state dynamics simulations of cycloparaphenylene chromophores provide a simple and conceptually appealing physical picture explaining experimentally observed trends in optical properties in this family of molecules. Fully delocalized degenerate second and third excitonic states define linear absorption spectra. Self-trapping of the lowest excitonic state due to electron-phonon coupling leads to the formation of spatially localized excitation in large cycloparaphenylenes within 100 fs. This invalidates the commonly used Condon approximation and breaks optical selection rules, making these materials superior fluorophores. This process does not occur in the small molecules, which remain inefficient emitters. A complex interplay of symmetry, π-conjugation, conformational distortion and bending strain controls all photophysics of cycloparaphenylenes.Fil: Adamska, Lyudmyla. Los Alamos National Laboratory. Los Alamos; Estados UnidosFil: Nayyar, Iffat. Los Alamos National Laboratory. Los Alamos; Estados UnidosFil: Chen, Hang. Boston University; Estados UnidosFil: Swan, Anna K.. Boston University; Estados UnidosFil: Oldani, Andres Nicolas. Universidad Nacional de Quilmes; ArgentinaFil: Fernández Alberti, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Golder, Matthew R.. University of Oregon; Estados UnidosFil: Jasti, Ramesh. University of Oregon; Estados UnidosFil: Doorn, Stephen K.. Los Alamos National Laboratory. Los Alamos; Estados UnidosFil: Tretiak, Sergei. Los Alamos National Laboratory. Los Alamos; Estados Unido

(5′S)-8,5′-Cyclo-2′-deoxyguanosine Is a Strong Block to Replication, a Potent pol V-Dependent Mutagenic Lesion, and Is Inefficiently Repaired in Escherichia coli

8,5′-Cyclopurines, making up an important class of ionizing radiation-induced tandem DNA damage, are repaired only by nucleotide excision repair (NER). They accumulate in NER-impaired cells, as in Cockayne syndrome group B and certain Xeroderma Pigmentosum patients. A plasmid containing (5′S)-8,5′-cyclo-2′-deoxyguanosine (S-cdG) was replicated in Escherichia coli with specific DNA polymerase knockouts. Viability was \u3c1% in the wild-type strain, which increased to 5.5% with SOS. Viability decreased further in a pol II- strain, whereas it increased considerably in a pol IV- strain. Remarkably, no progeny was recovered from a pol V- strain, indicating that pol V is absolutely required for bypassing S-cdG. Progeny analyses indicated that S-cdG is significantly mutagenic, inducing ∼34% mutation with SOS. Most mutations were S-cdG → A mutations, though S-cdG → T mutation and deletion of 5′C also occurred. Incisions of purified UvrABC nuclease on S-cdG, S-cdA, and C8-dG-AP on a duplex 51-mer showed that the incision rates are C8-dG-AP \u3e S-cdA \u3e S-cdG. In summary, S-cdG is a major block to DNA replication, highly mutagenic, and repaired slowly in E. coli

Proton-Binding Sites of Acid-Sensing Ion Channel 1

Acid-sensing ion channels (ASICs) are proton-gated cation channels that exist throughout the mammalian central and peripheral nervous systems. ASIC1 is the most abundant of all the ASICs and is likely to modulate synaptic transmission. Identifying the proton-binding sites of ASCI1 is required to elucidate its pH-sensing mechanism. By using the crystal structure of ASIC1, the protonation states of each titratable site of ASIC1 were calculated by solving the Poisson-Boltzmann equation under conditions wherein the protonation states of all these sites are simultaneously in equilibrium. Four acidic-acidic residue pairs—Asp238-Asp350, Glu220-Asp408, Glu239-Asp346, and Glu80-Glu417—were found to be highly protonated. In particular, the Glu80-Glu417 pair in the inner pore was completely protonated and possessed 2 H+, implying its possible importance as a proton-binding site. The pKa of Glu239, which forms a pair with a possible pH-sensing site Asp346, differs among each homo-trimer subunit due to the different H-bond pattern of Thr237 in the different protein conformations of the subunits. His74 possessed a pKa of ≈6–7. Conservation of His74 in the proton-sensitive ASIC3 that lacks a residue corresponding to Asp346 may suggest its possible pH-sensing role in proton-sensitive ASICs