Exploiting boundary states of imperfect spin chains for high-fidelity state transfer

We study transfer of a quantum state through XX spin chains with static imperfections. We combine the two standard approaches for state transfer based on (i) modulated couplings between neighboring spins throughout the spin chain and (ii) weak coupling of the outermost spins to an unmodulated spin chain. The combined approach allows us to design spin chains with modulated couplings and localized boundary states, permitting high-fidelity state transfer in the presence of random static imperfections of the couplings. The modulated couplings are explicitly obtained from an exact algorithm using the close relation between tridiagonal matrices and orthogonal polynomials [Linear Algebr. Appl. 21, 245 (1978)]. The implemented algorithm and a graphical user interface for constructing spin chains with boundary states (spinGUIn) are provided as Supplemental Material.Comment: 7 pages, 3 figures + spinGUIn description and Matlab files iepsolve.m, spinGUIn.fig, spinGUIn.

NMR approach for monitoring the photo-degradation of riboflavin and methionine

The light exposure of white wine is responsible for several reactions leading to changes on colour, flavours and, consequently, affecting the sensory profile. These reactions can take place when the white wine is bottled in clear glass and their mechanisms are dependent on both light exposure and chemical composition of white wine. Particular attention has been given to the reaction involving riboflavin (RF), a photo-sensitizer compound, and methionine (Met), a sulfur-containing amino acid, that can cause the formation of volatile sulphur compounds (VSCs), namely methanethiol and dimethyl disulfide. These compounds are responsible for a defect known as light-struck taste. Previous studies showed that hydrolysable tannins, in particular those from nut galls, limited both the degradation of Met and the formation of VSCs. The effectiveness of hydrolysable tannins was also proved after light exposure and storage for 24 months. In order to better understand the role of tannins in the photo-degradative reactions, an NMR approach was carried out. A solution containing RF (0.2 mM) and Met (2 mM) acidified at pH 3.2 was exposed to light by using fluorescence light bulbs. The solution was exposed to light up to two hours sampling it every 15 minutes. The same experimental conditions were applied in presence of gallic acid (2 mM), a constitutive unit of nut gall tannins. The degradation of RF and Met was monitored and, as expected, their signals decreased as the light exposure increased. Results provided evidence that a new signal appeared at 2.64 ppm. This signal was assigned to the SOCH3 moiety of methionine sulfoxide through the addition of the standard solution and standard 2D-NMR assignment techniques. The formation kinetic of methionine sulfoxide was measured for increased duration of light exposure and its rate resulted two-folds lower with the addition of gallic acid. This result suggests that the limited degradation of Met in presence of tannins, also observed in previous studies, is due to their action as competitor with Met in reducing RF from its excited form. The NMR technique was suitable for monitoring the photo-degradative reaction of RF and Met. Further researches have been carried out in order to verify and prove the ability of tannins in quenching both singlet oxygen and RF

Evidence for BCR/ABL1‐positive T‐cell acute lymphoblastic leukemia arising in an early lymphoid progenitor cell

BCR‐ABL1‐positive leukemias have historically been classified as either chronic myelogenous leukemia or Ph+ acute lymphoblastic leukemia. Recent analyses suggest there may be a wider range of subtypes. We report a patient with BCR‐ABL1 fusion positive T‐cell ALL with a previously undescribed cell distribution of the fusion gene. The examination of sorted cells by fluorescence in situ hybridization showed the BCR‐ABL1 fusion in the malignant T cells and a subpopulation of the nonmalignant B cells, but not nonmalignant T cells or myeloid or CD34+ progenitor cells providing evidence that the fusion may have occurred in an early lymphoid progenitor

Use of varenicline for smoking cessation treatment in UK primary care: an association rule mining analysis

BACKGROUND: Varenicline is probably the most effective smoking cessation pharmacotherapy, but is less widely used than nicotine replacement therapy. We therefore set out to identify the characteristics of numerically important groups of patients who typically do, or do not, receive varenicline in the UK. METHODS: We used association rule mining to analyse data on prescribing of smoking cessation pharmacotherapy in relation to age, sex, comorbidity and other variables from 477,620 people aged 16 years and over, registered as patients throughout 2011 with one of 559 UK general practices in The Health Improvement Network (THIN) database, and recorded to be current smokers. RESULTS: 46,685 participants (9.8% of all current smokers) were prescribed any smoking cessation treatment during 2011, and 19,316 of these (4% of current smokers, 41% of those who received any therapy) were prescribed varenicline. Prescription of varenicline was most common among heavy smokers aged 31–60, and in those with a diagnosis of COPD. Varenicline was rarely used among smokers who were otherwise in good health, or were aged over 60, were lighter smokers, or had psychotic disorders or dementia. CONCLUSIONS: Varenicline is being underused in healthy smokers, or in older smokers, and in those with psychotic disorders or dementia. Since varenicline is probably the most effective available single cessation therapy, this study identifies under-treatment of substantial public health significance

β-hairpin-mediated formation of structurally distinct multimers of neurotoxic prion peptides

Protein misfolding disorders are associated with conformational changes in specific proteins, leading to the formation of potentially neurotoxic amyloid fibrils. During pathogenesis of prion disease, the prion protein misfolds into β-sheet rich, protease-resistant isoforms. A key, hydrophobic domain within the prion protein, comprising residues 109–122, recapitulates many properties of the full protein, such as helix-to-sheet structural transition, formation of fibrils and cytotoxicity of the misfolded isoform. Using all-atom, molecular simulations, it is demonstrated that the monomeric 109–122 peptide has a preference for α-helical conformations, but that this peptide can also form β-hairpin structures resulting from turns around specific glycine residues of the peptide. Altering a single amino acid within the 109–122 peptide (A117V, associated with familial prion disease) increases the prevalence of β-hairpin formation and these observations are replicated in a longer peptide, comprising residues 106–126. Multi-molecule simulations of aggregation yield different assemblies of peptide molecules composed of conformationally-distinct monomer units. Small molecular assemblies, consistent with oligomers, comprise peptide monomers in a β-hairpin-like conformation and in many simulations appear to exist only transiently. Conversely, larger assemblies are comprised of extended peptides in predominately antiparallel β-sheets and are stable relative to the length of the simulations. These larger assemblies are consistent with amyloid fibrils, show cross-β structure and can form through elongation of monomer units within pre-existing oligomers. In some simulations, assemblies containing both β-hairpin and linear peptides are evident. Thus, in this work oligomers are on pathway to fibril formation and a preference for β-hairpin structure should enhance oligomer formation whilst inhibiting maturation into fibrils. These simulations provide an important new atomic-level model for the formation of oligomers and fibrils of the prion protein and suggest that stabilization of β-hairpin structure may enhance cellular toxicity by altering the balance between oligomeric and fibrillar protein assemblies

Balancing repair and tolerance of DNA damage caused by alkylating agents

Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for a favourable response of an organism to alkylating agents. Furthermore, the response of an individual to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity

Macromolecular Traits in the African Rice Oryza glaberrima and in Glaberrima/Sativa Crosses, and Their Relevance to Processing

Molecular properties of proteins and starch were investigated in 2 accessions of Oryza glaberrima and Oryza sativa, and in one NERICA cross between the 2 species, to assess traits that could be relevant to transformation into specific foods. Protein nature and organization in O. glaberrima were different from those in O. sativa and in NERICA. Despite the similar cysteine content in all samples, thiol accessibility in O. glaberrima proteins was higher than in NERICA or in O. sativa. Inter-protein disulphide bonds were important for the formation of protein aggregates in O. glaberrima, whereas non-covalent protein-protein interactions were relevant in NERICA and O. sativa. DSC and NMR studies indicated only minor differences in the structure of starch in these species, as also made evident by their microstructural features. Nevertheless, starch gelatinization in O. glaberrima was very different from what was observed in O. sativa and NERICA. The content of soluble species in gelatinized starch from the various species in the presence/absence of treatments with specific enzymes indicated that release of small starch breakdown products was lowest in O. glaberrima, in particular from the amylopectin component. These findings may explain the low glycemic index of O. glaberrima, and provide a rationale for extending the use of O. glaberrima in the production of specific rice-based products, thus improving the economic value and the market appeal of African crops

Streptococcus thermophilus urease activity boosts Lactobacillus delbrueckii subsp. bulgaricus homolactic fermentation

The proto-cooperation between Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus in the yogurt consortium enhances the growth rate and size of each population. In contrast, the independent growth of the two species in milk leads to a slower growth rate and a smaller population size. In this study, we report the first evidence that the urease activity of S. thermophilus increases the intracellular pH of L. delbrueckii in the absence of carbon source. However, in milk, in the presence of lactose the alkalizing effect of urea-derived ammonia was not detectable. Nevertheless, based on glucose consumption and lactic acid production at different pHin, L. delbrueckii showed an optimum of glycolysis and homolactic fermentation at alkaline pH values. In milk, we observed that ammonia provided by urea hydrolysis boosted lactic acid production in S. thermophilus and in L. delbrueckii when the species were grown alone or in combination. Therefore, we propose that urease activity acts as an altruistic cooperative trait, which is costly for urease-positive individuals but provides a local benefit because other individuals can take advantage of urease-dependent ammonia release

α-Synuclein is a Novel Microtubule Dynamase.

α-Synuclein is a presynaptic protein associated to Parkinson's disease, which is unstructured when free in the cytoplasm and adopts α helical conformation when bound to vesicles. After decades of intense studies, α-Synuclein physiology is still difficult to clear up due to its interaction with multiple partners and its involvement in a pletora of neuronal functions. Here, we looked at the remarkably neglected interplay between α-Synuclein and microtubules, which potentially impacts on synaptic functionality. In order to identify the mechanisms underlying these actions, we investigated the interaction between purified α-Synuclein and tubulin. We demonstrated that α-Synuclein binds to microtubules and tubulin α2β2 tetramer; the latter interaction inducing the formation of helical segment(s) in the α-Synuclein polypeptide. This structural change seems to enable α-Synuclein to promote microtubule nucleation and to enhance microtubule growth rate and catastrophe frequency, both in vitro and in cell. We also showed that Parkinson's disease-linked α-Synuclein variants do not undergo tubulin-induced folding and cause tubulin aggregation rather than polymerization. Our data enable us to propose α-Synuclein as a novel, foldable, microtubule-dynamase, which influences microtubule organisation through its binding to tubulin and its regulating effects on microtubule nucleation and dynamics