Aroma components of Galician Albariño, Loureira and Godello wines

Wines of the three most interesting Galician white grape varieties have been deeply analyzed for three aroma categories: the volatile compounds, except for monoterpenols, the monoterpenols and the bound forms. Many compounds showed significant differences between the wine groups, as proved by Tukey's test, e.g. for methanol, trans and cis 3-hexen-1-ols and relevant ratio, benzaldehyde and 4-vinylguaiacol in the first category, and for the most part of compounds of the other two categories. Loureira and most Albariño wines contain linalool and ho-trienol at a level of sensorial contribution. The relevant average terpene profiles show many similarities, especially for Albariño and particularly if considering the contents and relevant ratios of furan and pyran linalool oxide isomers, of ho-diendiols I and II and of geraniol. On the other hand differences could be stated for some compounds, mostly under the bound forms. Godello wines, with the poorest content of monoterpenols under both forms, are principally characterized by a marked level of bound benzaldehyde, with contemporary presence of a considerable average level of the free form. PCA data treatments on both monoterpenols and aglycons from the bound forms, showed a good separation among the groups as well a good homogeneity and varietal correspondence of the wines

γ-Hemolysin oligomeric structure and effect of its formation on supported lipid bilayers: An AFM Investigation.

γ-Hemolysins are bicomponent β-barrel pore forming toxins produced by Staphylococcus aureus as water-soluble monomers, which assemble into oligomeric pores on the surface of lipid bilayers. Here, after investigating the oligomeric structure of γ-hemolysins on supported lipid bilayers (SLBs) by atomic force microscopy (AFM), we studied the effect produced by this toxin on the structure of SLBs. We found that oligomeric structures with different number of monomers can assemble on the lipid bilayer being the octameric form the most stable one. Moreover, in this membrane model we found that γ-hemolysins can form clusters of oligomers inducing a curvature in the lipid bilayer, which could probably enhance the aggressiveness of these toxins at high concentrations

Methyl trans geranate and farnesoate as markers for Gewürztraminer grape skins and related distillates

Methyl ester of trans geranic and farnesoic acids, farnesol and two alpha-farnesene isomers are remarkable compounds in skins of mature grapes as well as in marc distillates of Traminer variety. Considerations about their level in both products of other floral varieties, like Yellow and Rose Muscats and Müller-Thurgau, as well as about their relationships with the main skin monoterpenols and other compounds, including two unidentified stereoisomeric sesquiterpenes present only in distillates, were discussed. Finally, results of PCA data treatments as for the distillates are show

Bartlett pear unsaturated ethyl deconoates and C9 compounds among components characterizing cv. Catalan roxo grape marc distillates

Catalan roxo marc distillates contain compounds at an unusual level in a grape derivate. The most peculiar are several unsaturated ethyl decanoates typical of Bartlett pear distillates and derived from ethyl esters found in the grape skins, some of which partially modified in the stereoisomery probably by the fermentation process. Remarkable compounds are unbranched aliphatic C-9 compounds at different oxidation state as well as ethyl nonanoate. At sensorially interesting levels methyl and ethyl salicylate and ethyl cinnamate, monoterpenols typical of floral-like varieties, vitispiranes and 4-ethylguaiacol are detected. Methyl salicylate is found in the berry as free and bound compound as several monoterpenols

Controllable Chest X-Ray Report Generation from Longitudinal Representations

Radiology reports are detailed text descriptions of the content of medical scans. Each report describes the presence/absence and location of relevant clinical findings, commonly including comparison with prior exams of the same patient to describe how they evolved. Radiology reporting is a time-consuming process, and scan results are often subject to delays. One strategy to speed up reporting is to integrate automated reporting systems, however clinical deployment requires high accuracy and interpretability. Previous approaches to automated radiology reporting generally do not provide the prior study as input, precluding comparison which is required for clinical accuracy in some types of scans, and offer only unreliable methods of interpretability. Therefore, leveraging an existing visual input format of anatomical tokens, we introduce two novel aspects: (1) longitudinal representation learning -- we input the prior scan as an additional input, proposing a method to align, concatenate and fuse the current and prior visual information into a joint longitudinal representation which can be provided to the multimodal report generation model; (2) sentence-anatomy dropout -- a training strategy for controllability in which the report generator model is trained to predict only sentences from the original report which correspond to the subset of anatomical regions given as input. We show through in-depth experiments on the MIMIC-CXR dataset how the proposed approach achieves state-of-the-art results while enabling anatomy-wise controllable report generation.Comment: Accepted to the Findings of EMNLP 202

Pore Formation by Equinatoxin II, a Eukaryotic Protein Toxin, Occurs by Induction of Nonlamellar Lipid Structures

Pore formation in the target cell membranes is a common mechanism used by many toxins in order to kill cells. Among various described mechanisms, a toroidal pore concept was described recently in the course of action of small antimicrobial peptides. Here we provide evidence that such mechanism may be used also by larger toxins. Membrane-destabilizing effects of equinatoxin II, a sea anemone cytolysin, were studied by various biophysical techniques. 31P NMR showed an occurrence of an isotropic component when toxin was added to multilamellar vesicles and heated. This component was not observed with melittin, alpha-staphylococcal toxin, or myoglobin. It does not originate from isolated small lipid structures, since the size of the vesicles after the experiment was similar to the control without toxin. Electron microscopy shows occurrence of a honeycomb structure, previously observed only for some particular lipid mixtures. The analysis of FTIR spectra of the equinatoxin II-lipid complex showed lipid disordering that is consistent with isotropic component observed in NMR. Finally, the cation selectivity of the toxin-induced pores increased in the presence of negatively charged phosphatidic acid, indicating the presence of lipids in the conductive channel. The results are compatible with the toroidal pore concept that might be a general mechanism of pore formation for various membrane-interacting proteins or peptides

Insights on Channel-Like Activity of Membrane Bound Alpha-Synuclein

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DOPAL derived alpha-synuclein oligomers impair synaptic vesicles physiological function

Parkinson's disease is a neurodegenerative disorder characterized by the death of dopaminergic neurons and by accumulation of alpha-synuclein (aS) aggregates in the surviving neurons. The dopamine catabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) is a highly reactive and toxic molecule that leads to aS oligomerization by covalent modifications to lysine residues. Here we show that DOPAL-induced aS oligomer formation in neurons is associated with damage of synaptic vesicles, and with alterations in the synaptic vesicles pools. To investigate the molecular mechanism that leads to synaptic impairment, we first aimed to characterize the biochemical and biophysical properties of the aS-DOPAL oligomers; heterogeneous ensembles of macromolecules able to permeabilise cholesterol-containing lipid membranes. aS-DOPAL oligomers can induce dopamine leak in an in vitro model of synaptic vesicles and in cellular models. The dopamine released, after conversion to DOPAL in the cytoplasm, could trigger a noxious cycle that further fuels the formation of aS-DOPAL oligomers, inducing neurodegeneration

Peptides corresponding to helices 5 and 6 of Bax can independently form large lipid pores

Proteins of the B-cell lymphoma protein 2 (Bcl2) family are key regulators of the apoptotic cascade, controlling the release of apoptotic factors from the mitochondrial intermembrane space. A helical hairpin found in the core of water-soluble folds of these proteins has been reported to be the pore- forming domain. Here we show that peptides including any of the two a-helix fragments of the hairpin of Bcl2 associated protein X (Bax) can independently induce release of large labelled dextrans from synthetic lipid vesicles. The permeability promoted by these peptides is influenced by intrinsic monolayer curvature and accompanied by fast transbilayer redis- tribution of lipids, supporting a toroidal pore mechanism as in the case of the full-length protein. However, compared with the pores made by com- plete Bax, the pores made by the Bax peptides are smaller and do not need the concerted action of tBid. These data indicate that the sequences of both fragments of the hairpin contain the principal physicochemical require- ments for pore formation, showing a parallel between the permeabilization mechanism of a complex regulated protein system, such as Bax, and the much simpler pore-forming antibiotic peptides

Single-molecule FRET studies on alpha-synuclein oligomerization of Parkinson's disease genetically related mutants.

Oligomers of alpha-synuclein are toxic to cells and have been proposed to play a key role in the etiopathogenesis of Parkinson's disease. As certain missense mutations in the gene encoding for alpha-synuclein induce early-onset forms of the disease, it has been suggested that these variants might have an inherent tendency to produce high concentrations of oligomers during aggregation, although a direct experimental evidence for this is still missing. We used single-molecule Förster Resonance Energy Transfer to visualize directly the protein self-assembly process by wild-type alpha-synuclein and A53T, A30P and E46K mutants and to compare the structural properties of the ensemble of oligomers generated. We found that the kinetics of oligomer formation correlates with the natural tendency of each variant to acquire beta-sheet structure. Moreover, A53T and A30P showed significant differences in the averaged FRET efficiency of one of the two types of oligomers formed compared to the wild-type oligomers, indicating possible structural variety among the ensemble of species generated. Importantly, we found similar concentrations of oligomers during the lag-phase of the aggregation of wild-type and mutated alpha-synuclein, suggesting that the properties of the ensemble of oligomers generated during self-assembly might be more relevant than their absolute concentration for triggering neurodegeneration.LT has been recipient of a grant PAT Post Doc Outgoing 2009 – 7th Framework Program Marie Curie COFUND actions. NC was funded by a Royal Society Dorothy Hodgkin Research Fellowship and is currently a Ramón y Cajal Research Fellow (Spanish Ministry of Economy and Competitiveness). MHH thanks the Royal Society of Chemistry (Analytical Chemistry Trust Fund) for his studentship. AJD is funded by the Schiff Foundation.This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/srep1669