Elucidation of the disulfide folding pathway of hirudin by a topology-based approach

A theoretical model for the folding of proteins containing disulfide bonds is introduced. The model exploits the knowledge of the native state to favour the progressive establishment of native interactions. At variance with traditional approaches based on native topology, not all native bonds are treated in the same way; in particular, a suitable energy term is introduced to account for the special strength of disulfide bonds (irrespective of whether they are native or not) as well as their ability to undergo intra-molecular reshuffling. The model thus possesses the minimal ingredients necessary to investigated the much debated issue of whether the re-folding process occurs through partially structured intermediates with native or non-native disulfide bonds. This strategy is applied to a context of particular interest, the re-folding process of Hirudin, a thrombin-specific protease inhibitor, for which conflicting folding pathways have been proposed. We show that the only two parameters in the model (temperature and disulfide strength) can be tuned to reproduce well a set of experimental transitions between species with different number of formed disulfide. This model is then used to provide a characterisation of the folding process and a detailed description of the species involved in the rate-limiting step of Hirudin refolding.Comment: 14 pages, 9 figure

Characterizing the nature of Fossil Groups with XMM

We present an X-ray follow-up, based on XMM plus Chandra, of six Fossil Group (FG) candidates identified in our previous work using SDSS and RASS data. Four candidates (out of six) exhibit extended X-ray emission, confirming them as true FGs. For the other two groups, the RASS emission has its origin as either an optically dull/X-ray bright AGN, or the blending of distinct X-ray sources. Using SDSS-DR7 data, we confirm, for all groups, the presence of an r-band magnitude gap between the seed elliptical and the second-rank galaxy. However, the gap value depends, up to 0.5mag, on how one estimates the seed galaxy total flux, which is greatly underestimated when using SDSS (relative to Sersic) magnitudes. This implies that many FGs may be actually missed when using SDSS data, a fact that should be carefully taken into account when comparing the observed number densities of FGs to the expectations from cosmological simulations. The similarity in the properties of seed--FG and non-fossil ellipticals, found in our previous study, extends to the sample of X-ray confirmed FGs, indicating that bright ellipticals in FGs do not represent a distinct population of galaxies. For one system, we also find that the velocity distribution of faint galaxies is bimodal, possibly showing that the system formed through the merging of two groups. This undermines the idea that all selected FGs form a population of true fossils.Comment: 9 pages, 3 figures. Submitted 01/12/2011 to MNRAS, referee report received 21/02/2012, accepted 22/02/201

Search for charginos nearly mass-degenerate with the lightest neutralino e+e−e^+e^- collisions up to s\sqrt{s} = 209GeV

Search for chargino nearly mass-degenerate with the lightest neutralino is performed with the data collected at a centre-of-mass energy from 189 to 209~GeV by the ALEPH detector at LEP. The analysis uses the detection of an isolated and energetic initial state radiation photon, produced in association with the chargino pair, whose decay products have small visible energy. No evidence of signal is found and lower limits on the chargino mass of 91 and 89~GeV/$c^2$ at 95\% confidence level are derived, for large scalar masses, in gaugino and in higgsino region respectively

Specific Microbial Communities Are Selected in Minimally-Processed Fruit and Vegetables according to the Type of Product

Fruits and vegetables (F&V) products are recommended for the daily diet due to their low caloric content, high amount of vitamins, minerals and fiber. Furthermore, these foods are a source of various phytochemical compounds, such as polyphenols, flavonoids and sterols, exerting antioxidant activity. Despite the benefits derived from eating raw F&V, the quality and safety of these products may represent a source of concern, since they can be quickly spoiled and have a very short shelf-life. Moreover, they may be a vehicle of pathogenic microorganisms. This study aims to evaluate the bacterial and fungal populations in F&V products (i.e., iceberg lettuces, arugula, spinaches, fennels, tomatoes and pears) by using culture-dependent microbiological analysis and high-throughput sequencing (HTS), in order to decipher the microbial populations that characterize minimally-processed F&V. Our results show that F&V harbor diverse and product-specific bacterial and fungal communities, with vegetables leaf morphology and type of edible fraction of fruits exerting the highest influence. In addition, we observed that several alterative (e.g., Pseudomonas and Aspergillus) and potentially pathogenic taxa (such as Staphylococcus and Cladosporium) are present, thus emphasizing the need for novel product-specific strategies to control the microbial composition of F&V and extend their shelf-life

Detection of Zak phases and topological invariants in a chiral quantum walk of twisted photons

Topological insulators are fascinating states of matter exhibiting protected edge states and robust quantized features in their bulk. Here, we propose and validate experimentally a method to detect topological properties in the bulk of one-dimensional chiral systems. We first introduce the mean chiral displacement, and we show that it rapidly approaches a multiple of the Zak phase in the long time limit. Then we measure the Zak phase in a photonic quantum walk, by direct observation of the mean chiral displacement in its bulk. Next, we measure the Zak phase in an alternative, inequivalent timeframe, and combine the two windings to characterize the full phase diagram of this Floquet system. Finally, we prove the robustness of the measure by introducing dynamical disorder in the system. This detection method is extremely general, as it can be applied to all one-dimensional platforms simulating static or Floquet chiral systems.Comment: 10 pages, 7 color figures (incl. appendices) Close to the published versio

Similarities between skin culturable bacterial species of pool frogs (Pelophylax lessonae) and their habitat

The aim of the present study was to investigate the culturable microflora of pool frogs (Pelophylax lessonae) and their belonging aquatic environment. A total of 60 samples (56 frog cutaneous swabs, 4 water samples) were inoculated onto different selective and differential agar plates to isolate Grampositive and Gram-negative bacteria or yeasts. Microbial investigation of the water hosting frogs was also performed. Isolates were identified by API system and their antibiotic resistance profiles were evaluated by disk diffusion method on Mueller Hinton agar plates. Aeromonas hydrophila and Enterococcus durans were detected in almost all collected samples. Many of the bacterial isolates showed multidrug-resistant profiles. Importantly, this study highlights that skin frog microbiota is correlated to the belonging environment, and, moreover, some isolated bacterial strains resulted to be of interest in animal and public health, since the park was frequented by visitors of all ages

Exploring the immune-checkpoint inhibitors' efficacy/tolerability in special non-small cell lung cancer (NSCLC) populations: Focus on steroids and autoimmune disease

The advent of immune-checkpoint inhibitors targeting the programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) axis, both as monotherapy and in combination strategies, produced a paradigm change of the treatment algorithm for metastatic, non-oncogene addicted, non-small cell lung cancer (NSCLC) patients. Although the great efficacy and the optimal tolerability emerging from clinical studies has been confirmed for the majority of patients treated in the real-word scenario, however the potential activity and safety profile of these agents in uncommon NSCLC populations remains still controversial. Particularly, patients with previously diagnosed autoimmune disease or concomitant steroids treatment at the time of immunotherapy initiation represent two special subgroups of patients not unusual in the real-word practice, to whom the clinical implication of immune-checkpoint inhibitors administration is largely unknown. In this review we provided an updated literature overview, summarizing available evidence and reporting practical suggestions, which may guide physicians in their clinical management of these NSCLC sub-populations

Unusual sub-genus associations of fecal Prevotella and Bacteroides with specific dietary patterns

Background: Diet has a recognized effect in shaping gut microbiota. Many studies link an increase in Prevotella to high-fibre diet, while Bacteroides abundance is usually associated with the consumption of animal fat and protein-rich diets. Nevertheless, closely related species and strains may harbour different genetic pools; therefore, further studies should aim to understand whether species of the same genus are consistently linked to dietary patterns or equally responsive to diet variations. Here, we used oligotyping of 16S rRNA gene sequencing data to exploit the diversity within Prevotella and Bacteroides genera in faecal samples of omnivore and non-omnivore subjects from a previously studied cohort. Results: A great heterogeneity was found in oligotype composition. Nevertheless, different oligotypes within the same genus showed distinctive correlation patterns with dietary components and metabolome. We found that some Prevotella oligotypes are significantly associated with the plant-based diet but some are associated with animal-based nutrients, and the same applies to Bacteroides. Therefore, an indiscriminate association of Bacteroidetes genera with specific dietary patterns may lead to an oversimplified vision that does not take into account sub-genus diversity and the different possible responses to dietary components. Conclusions: We demonstrated that Prevotella and Bacteroides oligotypes show distinctive correlation patterns with dietary components and metabolome. These results substantiate a current oversimplification of diet-dependent microbe-host associations and highlighted that sub-genus differences must be taken into account when planning gut microbiota modulation for health benefits