The phenotypic characterization of yeast strains to stresses inherent to wine fermentation in warm climates.

AIMS: Climate change is exerting an increasingly profound effect on grape composition, microbiology, chemistry and the sensory aspects of wine. Identification of autochthonous yeasts tolerant to stress could help to alleviate this effect. METHODS AND RESULTS: Tolerance to osmotic pressure, ethanol and pH of 94 Saccharomyces cerevisiae strains and 29 strains non-Saccharomyces from the warm climate region DO 'Vinos de Madrid' (Spain) using phenotypic microarray and their fermentative behaviour were studied. The screening highlighted 12 strains of S. cerevisiae isolated from organic cellars with improved tolerance to osmotic stress, high ethanol concentrations and suitable fermentative properties. Screening of non-Saccharomyces spp. such as Lanchacea thermotolerans, Torulaspora delbrueckii, Schizosaccharomyces pombe and Mestchnikowia pulcherrima also highlighted tolerance to these stress conditions. CONCLUSIONS: This study confirmed the adaptation of native strains to the climatic conditions in each area of production and correlated these adaptations with good fermentation properties. Screening has revealed that identifying yeast strains adapted to fermentation stresses is an important approach for making quality wines in very warm areas. SIGNIFICANCE AND IMPACT OF THE STUDY: The results have special relevance because it is a pioneering study that has approached the problem of climate change for wines from a microbiological aspect and has analysed the situation in situ in wineries from a warm climate zone. Resistant strains were found with good biological properties; studying these strains for their stress response mechanisms during fermentation will be of interest to the wine making industry.

Genetic diversity in commercial wineries: effects of the farming system and vinification management on wine yeasts.

AIMS: Analysis of the diversity and distribution of wine yeasts isolated from organically and conventionally grown grapes, and during the subsequent fermentation with or without starter cultures in six different commercial wineries. METHODS AND RESULTS: PCR-RFLP screening of isolates revealed the involvement of ten different species. Saccharomyces cerevisiae, scarcely isolated from grapes, was the dominant species during the latter phases of fermentation, identifying 108 different genotypes by means of SSR analysis. Species and strains' diversity and presence were strongly influenced by the farming system used to grow the grapes and the system of vinification. CONCLUSIONS: Organic farming management was more beneficial in terms of diversity and abundance than the conventional one. Induced fermentation generated a great replacement of native yeasts. Although winery-resident yeasts resulted to be predominant in the process, some noncommercial strains originally in the vineyard were found in final stages of the fermentation, confirming that autochthonous strains of S. cerevisiae are capable to conduct the fermentation process up to its end. SIGNIFICANCE AND IMPACT OF THE STUDY: The study of natural yeast communities from commercial vineyards and wineries is an important step towards the preservation of native genetic resources. Our results have special relevance because it is the first time that the real situation of the yeast ecology of alcoholic fermentation in commercial wineries belonging to the relevant wine-producing Appellation of Origin 'Vinos de Madrid' is shown.

The impact of active dry yeasts in commercial wineries from the Denomination of Origen "Vinos de Madrid", Spain.

This paper has studied the success of implantation for 16 commercial active dry yeasts (ADYs) during industrial fermentation (30) and the impact of these yeasts during spontaneous fermentations (19) in 10 wineries from the Denomination of Origin "Vinos de Madrid" over two consecutive years. Yeasts strains were identified by molecular techniques, pulsed field electrophoresis and microsatellite analysis. According to these techniques, all the ADYs were different with the exceptions of two strains, L2056 and Rh, which showed the same karyotype and loci size. The results showed that inoculating fermentations with ADYs did not ensure their dominance throughout the fermentation; the implantation level of ADYs was above 80% in only 9 of the 30 commercial fermentations studied; while in 16 fermentations, the dominance of the inoculated ADYs was below 50%. The type of vinification with the best implantation results overall were those associated with red wine fermentations. ADYs affected spontaneous fermentations, although their impact was observed to decrease in the second year of the study. Therefore, specific adaptation studies are necessary before using commercial yeasts during the fermentation process. At the same time, a study was carried out on the frequency of commercial strains in IMIDRA's yeast collection, made up of strains isolated from spontaneous fermentations of the different areas and cellars since the beginning of the Denomination of Origin "Vinos de Madrid" in 1990. Six different ADYs were found with a frequency of less than 5%.

Physiologically based mathematical models of nanomaterials for regulatory toxicology: A review.

The development of physiologically based (PB) models to support safety assessments in the field of nanotechnology has grown steadily during the last decade. This review reports on the availability of PB models for toxicokinetic (TK) and toxicodynamic (TD) processes, including in vitro and in vivo dosimetry models applied to manufactured nanomaterials (MNs). In addition to reporting on the state-of-the-art in the scientific literature concerning the availability of physiologically based kinetic (PBK) models, we evaluate their relevance for regulatory applications, mainly considering the EU REACH regulation. First, we performed a literature search to identify all available PBK models. Then, we systematically reported the content of the identified papers in a tailored template to build a consistent inventory, thereby supporting model comparison. We also described model availability for physiologically based dynamic (PBD) and in vitro and in vivo dosimetry models according to the same template. For completeness, a number of classical toxicokinetic (CTK) models were also included in the inventory. The review describes the PBK model landscape applied to MNs on the basis of the type of MNs covered by the models, their stated applicability domain, the type of (nano-specific) inputs required, and the type of outputs generated. We identify the main assumptions made during model development that may influence the uncertainty in the final assessment, and we assess the REACH relevance of the available models within each model category. Finally, we compare the state of PB model acceptance for chemicals and for MNs. In general, PB model acceptance is limited by the absence of standardised reporting formats, psychological factors such as the complexity of the models, and technical considerations such as lack of blood:tissue partitioning data for model calibration/validation.

Computational models for the assessment of manufactured nanomaterials: Development of model reporting standards and mapping of the model landscape.

Different types of computational models have been developed for predicting the biokinetics, environmental fate, exposure levels and toxicological effects of chemicals and manufactured nanomaterials (MNs). However, these models are not described in a consistent manner in the scientific literature, which is one of the barriers to their broader use and acceptance, especially for regulatory purposes. Quantitative structure-activity relationships (QSARs) are in silico models based on the assumption that the activity of a substance is related to its chemical structure. These models can be used to provide information on (eco)toxicological effects in hazard assessment. In an environmental risk assessment, environmental exposure models can be used to estimate the predicted environmental concentration (PEC). In addition, physiologically based kinetic (PBK) models can be used in various ways to support a human health risk assessment. In this paper, we first propose model reporting templates for systematically and transparently describing models that could potentially be used to support regulatory risk assessments of MNs, for example under the REACH regulation. The model reporting templates include (a) the adaptation of the QSAR Model Reporting Format (QMRF) to report models for MNs, and (b) the development of a model reporting template for PBK and environmental exposure models applicable to MNs. Second, we show the usefulness of these templates to report different models, resulting in an overview of the landscape of available computational models for MNs.

Circulating miR-323-3p is a biomarker for cardiomyopathy and an indicator of phenotypic variability in Friedreich's ataxia patients.

MicroRNAs (miRNAs) are noncoding RNAs that contribute to gene expression modulation by regulating important cellular pathways. In this study, we used small RNA sequencing to identify a series of circulating miRNAs in blood samples taken from Friedreich's ataxia patients. We were thus able to develop a miRNA biomarker signature to differentiate Friedreich's ataxia (FRDA) patients from healthy people. Most research on FDRA has focused on understanding the role of frataxin in the mitochondria, and a whole molecular view of pathological pathways underlying FRDA therefore remains to be elucidated. We found seven differentially expressed miRNAs, and we propose that these miRNAs represent key mechanisms in the modulation of several signalling pathways that regulate the physiopathology of FRDA. If this is the case, miRNAs can be used to characterize phenotypic variation in FRDA and stratify patients' risk of cardiomyopathy. In this study, we identify miR-323-3p as a candidate marker for phenotypic differentiation in FRDA patients suffering from cardiomyopathy. We propose the use of dynamic miRNAs as biomarkers for phenotypic characterization and prognosis of FRDA.

[Urachal sinus: an unusual cause of recurrent umbilical discharge in adults]. / Uracosinus: una causa poco frecuente de onfalitis recurrente en adultos.

Urachal sinus is a rare congenital anomaly due to incomplete closure the urachus in the umbilical region, it is very rare in adults. 47-year-old male who arrived at our Emergency Department with recurrent umbilical discharge. Not response medical treatment (oral antibiotic and drainage). Abdominal computerized tomography scan confirmed the urachal sinus with omphalitis. Surgical complete excision with omphalectomy was performed. Any complications in the postoperative was observed.

CT and MRI Correlations in Patients with Suspected Cholesteatoma after Surgery.

The study of postoperative ear cavities in patients who underwent surgery for cholesteatoma is a difficult challenge for radiologists. In our study we make a correlation between CT and MRI findings, useful tools in patients with suspected residual or recurrent cholesteatoma. The use of different MRI sequences especially DWI can help radiologists to discriminate between cholesteatoma and other different processes.

In vivo and in vitro pharmacological characterization of SVT-40776, a novel M3 muscarinic receptor antagonist, for the treatment of overactive bladder.

BACKGROUND AND PURPOSE: Highly selective M(3) muscarinic receptor antagonists may represent a better treatment for overactive bladder syndrome, diminishing side effects. Cardiac side effects of non-selective antimuscarinics have been associated with activity at M(2) receptors as these receptors are mainly responsible for muscarinic receptor-dependent bradycardia. We have investigated a novel antimuscarinic, SVT-40776, highly selective for M(3) over M(2) receptors (Ki = 0.19 nmol.L(-1) for M(3) receptor affinity). This study reports the functional activity of SVT-40776 in the bladder, relative to its activity in atria. EXPERIMENTAL APPROACH: In vitro and ex vivo (oral dosing) inhibition of mouse detrusor and atrial contractile responses to carbachol were used to study the functional activity of SVT-40776. The in vivo efficacy of SVT-40776 was characterized by suppression of isovolumetric spontaneous bladder contractions in anaesthetized guinea pigs after intravenous administration. KEY RESULTS: SVT-40776 was the most potent in inhibiting carbachol-induced bladder contractions of the anti-cholinergic agents tested, without affecting atrial contractions over the same range of concentrations. SVT-40776 exhibited the highest urinary versus cardiac selectivity (199-fold). In the guinea pig in vivo model, SVT-40776 inhibited 25% of spontaneous bladder contractions at a very low dose (6.97 microg.kg(-1) i.v), without affecting arterial blood pressure. CONCLUSIONS AND IMPLICATIONS: SVT-40776 is a potent inhibitor of M(3) receptor-related detrusor contractile activity. The absence of effects on isolated atria preparations represents an interesting characteristic and suggests that SVT-40776 may lack unwanted cardiac effects; a feature especially relevant in a compound intended to treat mainly elderly patients.

[Carotid-cavernous fistulas. A report of two cases]. / Fístulas carótido-cavernosas. A propósito de dos casos.

Carotid-cavernous fistulas are uncommon anomalous communications between the venous cavernous sinus and the carotid arterial system. We present two cases studied at our center. We show the characteristic CT, MRI, and orbital ultrasound findings and review the relevant literature.