Direct measurement of DNA-mediated adhesion between lipid bilayers

Multivalent interactions between deformable mesoscopic units are ubiquitous in biology, where membrane macromolecules mediate the interactions between neighbouring living cells and between cells and solid substrates. Lately, analogous artificial materials have been synthesised by functionalising the outer surface of compliant Brownian units, for example emulsion droplets and lipid vesicles, with selective linkers, in particular short DNA sequences. This development extended the range of applicability of DNA as a selective glue, originally applied to solid nano and colloidal particles. On very deformable lipid vesicles, the coupling between statistical effects of multivalent interactions and mechanical deformation of the membranes gives rise to complex emergent behaviours, as we recently contributed to demonstrate [Parolini et al., Nature Communications, 2015, 6, 5948]. Several aspects of the complex phenomenology observed in these systems still lack a quantitative experimental characterisation and fundamental understanding. Here we focus on the DNA-mediated multivalent interactions of a single liposome adhering to a flat supported bilayer. This simplified geometry enables the estimate of the membrane tension induced by the DNA-mediated adhesive forces acting on the liposome. Our experimental investigation is completed by morphological measurements and the characterisation of the DNA-melting transition, probed by in-situ F\"{o}rster Resonant Energy Transfer spectroscopy. Experimental results are compared with the predictions of an analytical theory that couples the deformation of the vesicle to a full description of the statistical mechanics of mobile linkers. With at most one fitting parameter, our theory is capable of semi-quantitatively matching experimental data, confirming the quality of the underlying assumptions.Comment: 16 pages, 7 figure

The mutual interplay of gut microbiota, diet and human disease

The intestinal milieu harbours the gut microbiota, consisting of a complex community of bacteria, archaea, fungi, viruses, and protozoans that bring to the host organism an endowment of cells and genes more numerous than its own. In the last ten years, mounting evidence has highlighted the prominent influence of the gut mutualistic bacterial communities on human health. Microbial colonization occurs alongside with immune system development and plays a role in intestinal physiology. The community of the gut microbiota does not undergo significant fluctuations throughout adult life. However, bacterial infections, antibiotic treatment, lifestyle, surgery, and diet might profoundly affect it. Gut microbiota dysbiosis, defined as marked alterations in the amount and function of the intestinal microorganisms, is correlated with the aetiology of chronic non-communicable diseases, ranging from cardiovascular, neurologic, respiratory, and metabolic illnesses to cancer. In this review, we focus on the interplay among gut microbiota, diet, and host to provide a perspective on the role of microbiota and their unique metabolites in the pathogenesis and/or progression of various human disorders. We discuss interventions based on microbiome studies, i.e. faecal microbiota transplantation, probiotics, and prebiotics, to introduce the concept that correcting gut dysbiosis can ameliorate disease symptoms, thus offering a new approach toward disease treatment

A hybrid finite volume -- spectral element method for aeroacoustic problems

We propose a hybrid Finite Volume (FV) - Spectral Element Method (SEM) for modelling aeroacoustic phenomena based on the Lighthill's acoustic analogy. First the fluid solution is computed employing a FV method. Then, the sound source term is projected onto the acoustic grid and the inhomogeneous Lighthill's wave equation is solved employing the SEM. The novel projection method computes offline the intersections between the acoustic and the fluid grids in order to preserve the accuracy. The proposed intersection algorithm is shown to be robust, scalable and able to efficiently compute the geometric intersection of arbitrary polyhedral elements. We then analyse the properties of the projection error, showing that if the fluid grid is fine enough we are able to exploit the accuracy of the acoustic solver and we numerically assess the obtained theoretical estimates. Finally, we address two relevant aeroacoustic benchmarks, namely the corotating vortex pair and the noise induced by a laminar flow around a squared cylinder, to demonstrate in practice the effectiveness of the projection method when dealing with high order solvers. The flow computations are performed with OpenFOAM [46], an open-source finite volume library, while the inhomogeneous Lighthill's wave equation is solved with SPEED [31], an opensource spectral element library

Multiphysics simulation of corona discharge induced ionic wind

Ionic wind devices or electrostatic fluid accelerators are becoming of increasing interest as tools for thermal management, in particular for semiconductor devices. In this work, we present a numerical model for predicting the performance of such devices, whose main benefit is the ability to accurately predict the amount of charge injected at the corona electrode. Our multiphysics numerical model consists of a highly nonlinear strongly coupled set of PDEs including the Navier-Stokes equations for fluid flow, Poisson's equation for electrostatic potential, charge continuity and heat transfer equations. To solve this system we employ a staggered solution algorithm that generalizes Gummel's algorithm for charge transport in semiconductors. Predictions of our simulations are validated by comparison with experimental measurements and are shown to closely match. Finally, our simulation tool is used to estimate the effectiveness of the design of an electrohydrodynamic cooling apparatus for power electronics applications.Comment: 24 pages, 17 figure

Removal of metallic elements from real wastewater using zebra mussel bio-filtration process

The metallic element pollution is a serious environmental problem but still unsolved since these contaminants are released mainly by human activity, reaching all the environmental compartments. Traditional wastewater treatment plants are very efficient in removing metallic elements only when their concentration is in the order of mg/L, but are not able to remove them until \u3bcg/L, as it would be needed to cope with the water quality standards in low flow receptors. Therefore, the aim of our study was to evaluate the potential removal of some recalcitrant metallic elements to the classical treatments, by the natural process of bio-filtration performed by the invasive zebra mussel (Dreissena polymorpha). For this purpose we built a pilot-plant at the Milano-Nosedo wastewater treatment plant, where we placed about 40,000 D. polymorpha specimens appointed to the wastewater bio-filtration. The metallic element removal due to zebra mussel activity was evaluated in the treated wastewater with a plasma optical emission spectrometry (ICP-OES). Data obtained in these experiments showed an encouraging metallic element removal due to D. polymorpha activity; in particular, the total abatement (100%) of Cr after one day of bio-filtration exposure is remarkable. Therefore, this study encourages further research related with the use of bivalves as a new tool for the wastewater depuration process; in this regard, the contaminated mollusks used in the bio-filtration could be incinerated or stored in special landfills, as is also the case of traditional sewage sludge

Ciliary signalling and mechanotransduction in the pathophysiology of craniosynostosis

Craniosynostosis (CS) is the second most prevalent inborn craniofacial malformation; it results from the premature fusion of cranial sutures and leads to dimorphisms of variable severity. CS is clinically heterogeneous, as it can be either a sporadic isolated defect, more frequently, or part of a syndromic phenotype with mendelian inheritance. The genetic basis of CS is also extremely heterogeneous, with nearly a hundred genes associated so far, mostly mutated in syndromic forms. Several genes can be categorised within partially overlapping pathways, including those causing defects of the primary cilium. The primary cilium is a cellular antenna serving as a signalling hub implicated in mechanotransduction, housing key molecular signals expressed on the ciliary membrane and in the cilioplasm. This mechanical property mediated by the primary cilium may also represent a cue to understand the pathophysiology of non‐syndromic CS. In this review, we aimed to highlight the implication of the primary cilium components and active signalling in CS pathophysiology, dissecting their biological functions in craniofacial development and in suture biomechanics. Through an in‐depth revision of the literature and computational annotation of disease‐associated genes we categorised 18 ciliary genes involved in CS aetiology. Interestingly, a prevalent implication of midline sutures is observed in CS ciliopathies, possibly explained by the specific neural crest origin of the frontal bone

Effects of an antioxidant protective topical formulation on eye exposed to ultraviolet-irradiation: A study in rabbit animal model

Ultraviolet-radiation exerts a well-known role in the development of various ocular diseases and may contribute to the progress of age-related macular degeneration. Therefore, the use of compounds able to protect the eyes from UV-induced cellular damage is challenging. The aim of this study has been to test the protective effects of an antioxidant topical formulation against UV-induced damage in rabbit eyes. Twelve male rabbits were used. Animals were divided into 4 groups of 3 animals each. Control group (CG) did not receive any irradiation and/or eye drop. The other three experimental groups were treated as follows: the first group received only UVR irradiation for 30 min, without eye drop supplementation (Irradiation group, IG), the second (G30) and the third (G60) groups received UV irradiation for 30' and 60', respectively, and eye drop supplementation (riboflavin, d-α-tocopheryl polyethylene glycol, proline, glycine, lysine and leucine solution) every 15 min for three hours. In the IG group a significant increase of oxidized glutathione (GSSG) and hydrogen peroxide (H2O2) was recorded in the aqueous humor, whereas ascorbic acid levels were significantly lower when compared to control eyes. In the groups exposed to UVR rays for 30 min, and treated with the topical antioxidant formulation, the GSSG, H2O2 and ascorbic acid levels were similar to those recorded in controls, whereas in the G60 group the three markers significantly differ from control group. In the lens, a significant decrease of alpha tocopherol and total antioxidant capacity (TAC) was recorded in IG-animals as compared to control group, whereas malondialdehyde (MDA) levels were significantly higher in UV-induced eye than in control eyes. In the G30 groups the alpha tocopherol, MDA and TAC levels do not significantly differ from those recorded in controls, whereas in the G60 group these three markers significantly differ from control group. Present findings demonstrate that topical treatment with the antioxidant formulation used herein protects ocular structures from oxidative stress induced by UV exposure in in vivo animal model

effects of an antioxidant protective topical formulation on eye exposed to ultraviolet irradiation a study in rabbit animal model

Ultraviolet-radiation exerts a well-known role in the development of various ocular diseases and may contribute to the progress of age-related macular degeneration. Therefore, the use of compounds able to protect the eyes from UV-induced cellular damage is challenging. The aim of this study has been to test the protective effects of an antioxidant topical formulation against UV-induced damage in rabbit eyes. Twelve male rabbits were used. Animals were divided into 4 groups of 3 animals each. Control group (CG) did not receive any irradiation and/or eye drop. The other three experimental groups were treated as follows: the first group received only UVR irradiation for 30 min, without eye drop supplementation (Irradiation group, IG), the second (G30) and the third (G60) groups received UV irradiation for 30' and 60', respectively, and eye drop supplementation (riboflavin, d-α-tocopheryl polyethylene glycol, proline, glycine, lysine and leucine solution) every 15 min for three hours. In the IG group a significant increase of oxidized glutathione (GSSG) and hydrogen peroxide (H2O2) was recorded in the aqueous humor, whereas ascorbic acid levels were significantly lower when compared to control eyes. In the groups exposed to UVR rays for 30 min, and treated with the topical antioxidant formulation, the GSSG, H2O2 and ascorbic acid levels were similar to those recorded in controls, whereas in the G60 group the three markers significantly differ from control group. In the lens, a significant decrease of alpha tocopherol and total antioxidant capacity (TAC) was recorded in IG-animals as compared to control group, whereas malondialdehyde (MDA) levels were significantly higher in UV-induced eye than in control eyes. In the G30 groups the alpha tocopherol, MDA and TAC levels do not significantly differ from those recorded in controls, whereas in the G60 group these three markers significantly differ from control group. Present findings demonstrate that topical treatment with the antioxidant formulation used herein protects ocular structures from oxidative stress induced by UV exposure in in vivo animal model

Nanomedicine, a valuable tool for skeletal muscle disorders: Challenges, promises, and limitations

Muscular dystrophies are a group of rare genetic disorders characterized by progressive muscle weakness, which, in the most severe forms, leads to the patient's death due to cardiorespiratory problems. There is still no cure available for these diseases and significant effort is being placed into developing new strategies to either correct the genetic defect or to compensate muscle loss by stimulating skeletal muscle regeneration. However, the vast anatomical extension of the target tissue poses great challenges to these goals, highlighting the need for complementary strategies. Nanomedicine is an actively evolving field that merges nanotechnologies with biomedical and pharmaceutical sciences. It holds great potential in regenerative medicine, both in supporting tissue engineering and regeneration, and in optimizing drug and oligonucleotide delivery and gene therapy strategies. In this review, we will summarize the state-of-the-art in the field of nanomedicine applied to skeletal muscle regeneration. We will discuss the recent work toward the development of nanopatterned scaffolds for tissue engineering, the efforts in the synthesis of organic and inorganic nanoparticles for gene therapy and drug delivery applications, as well as their use as immune modulators. Although nanomedicine holds great promise for muscle and other degenerative diseases, many challenges still need to be systematically addressed to assure a smooth transition from the bench to the bedside. This article is categorized under: Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement

SUIHTER: A new mathematical model for COVID-19. Application to the analysis of the second epidemic outbreak in Italy

The COVID-19 epidemic is the last of a long list of pandemics that have affected humankind in the last century. In this paper, we propose a novel mathematical epidemiological model named SUIHTER from the names of the seven compartments that it comprises: susceptible uninfected individuals (S), undetected (both asymptomatic and symptomatic) infected (U), isolated (I), hospitalized (H), threatened (T), extinct (E), and recovered (R). A suitable parameter calibration that is based on the combined use of least squares method and Markov Chain Monte Carlo (MCMC) method is proposed with the aim of reproducing the past history of the epidemic in Italy, surfaced in late February and still ongoing to date, and of validating SUIHTER in terms of its predicting capabilities. A distinctive feature of the new model is that it allows a one-to-one calibration strategy between the model compartments and the data that are daily made available from the Italian Civil Protection. The new model is then applied to the analysis of the Italian epidemic with emphasis on the second outbreak emerged in Fall 2020. In particular, we show that the epidemiological model SUIHTER can be suitably used in a predictive manner to perform scenario analysis at national level.Comment: 25 page