Topological jamming of spontaneously knotted polyelectrolyte chains driven through a nanopore

The advent of solid state nanodevices allows for interrogating the physico-chemical properties of a polyelectrolyte chain by electrophoretically driving it through a nanopore. Salient dynamical aspects of the translocation process have been recently characterized by theoretical and computational studies of model polymer chains free from self-entanglement. However, sufficiently long equilibrated chains are necessarily knotted. The impact of such topological "defects" on the translocation process is largely unexplored, and is addressed in this study. By using Brownian dynamics simulations on a coarse-grained polyelectrolyte model we show that knots, despite being trapped at the pore entrance, do not "per se" cause the translocation process to jam. Rather, knots introduce an effective friction that increases with the applied force, and practically halts the translocation above a threshold force. The predicted dynamical crossover, which is experimentally verifiable, is of relevance in applicative contexts, such as DNA nanopore sequencing.Comment: 6 pages; 7 figure

Control of DNA minor groove width and Fis protein binding by the purine 2-amino group.

The width of the DNA minor groove varies with sequence and can be a major determinant of DNA shape recognition by proteins. For example, the minor groove within the center of the Fis-DNA complex narrows to about half the mean minor groove width of canonical B-form DNA to fit onto the protein surface. G/C base pairs within this segment, which is not contacted by the Fis protein, reduce binding affinities up to 2000-fold over A/T-rich sequences. We show here through multiple X-ray structures and binding properties of Fis-DNA complexes containing base analogs that the 2-amino group on guanine is the primary molecular determinant controlling minor groove widths. Molecular dynamics simulations of free-DNA targets with canonical and modified bases further demonstrate that sequence-dependent narrowing of minor groove widths is modulated almost entirely by the presence of purine 2-amino groups. We also provide evidence that protein-mediated phosphate neutralization facilitates minor groove compression and is particularly important for binding to non-optimally shaped DNA duplexes

Morphological traits of the "Pantesco" donkey

The Pantelleria donkey is mentioned in prestigious zootechnical texts and treatises of the late 19th and early 20th century Authors such as Chiari, Mascheroni, Dechambre and others. In ancient times, when the Arab colonial extension in the Mediterranean reached its peak, a number of donkeys was transferred to the isle of Pantelleria southwest from Sicily. They served as draft animals and means of locomotion. In this environment scarcely suitable for the breeding of farm animals, considering the geo-morphological conditions of the island one of the most precious and valued donkey races of the Mediterranean basin has its origins: the Pantelleria donkey. Unfortunately, during World War II, Pantelleria was transferred in one of the most important theatres of war in the Mediterranean and the few remaining subjects of the race, once highly esteemed and frequently exported, were almost extirpated. Since then, various efforts have been made to recover the "Pantesco" donkey, but only in 1989 the Regional Forest Administration launched a project to reconstitute this particular population. Owing to comprehensive and accurate research, three males and six females with a percentage of 80 to 90% of "Pantesco" blood could be recovered. The aim of this recovery plan was to prevent the loss of a genotype of great historical and biological value in Sicily no less than in other European and Asian regions. Currently the "Pantesco" donkey population finally registered at the general index of equine races and populations consists of 51 subjects. The objective of our study was to determine the morphological type of this donkey population in order to provide useful data for its ethnic identification. The most significant morphometric traits of the thirty "Pantesco" donkeys examined (15 brood-mares, 13 stallions and 2 colts; those born after 2004 -15 subjects were excluded from measurements ) were measured in an erect position, using Lydtin's stick, calliper and flexible meter, and the most significant morphometric indices were calculated in order to provide for a reliable identification of the morphological type. The data obtained mean values ± sd (withers height:123.35±4.28cm; rump height: 129.43±4.43cm; chest height: 51.88±3.38cm; chest breadth: 28.61±6.66cm; body length: 124.82±8.86cm; lateral conformation body index :99.12±4.71; longitudinal thoracic section index: 41.65±2.42; body proportion index: 84.58±3.79; thorax height index: 42.05±2.07; pelvic index: 27.82±4.16; head length index: 42,28±1.53 and dactylo-thoracic index: 11.28±0.85 ), suggest that the "Pantesco" population can be assigned to the dolichomorphic type

Lactoferrin's anti-cancer properties. Safety, selectivity, and wide range of action

Despite recent advances in cancer therapy, current treatments, including radiotherapy, chemotherapy, and immunotherapy, although beneficial, present attendant side effects and long-term sequelae, usually more or less affecting quality of life of the patients. Indeed, except for most of the immunotherapeutic agents, the complete lack of selectivity between normal and cancer cells for radio- and chemotherapy can make them potential antagonists of the host anti-cancer self-defense over time. Recently, the use of nutraceuticals as natural compounds corroborating anti-cancer standard therapy is emerging as a promising tool for their relative abundance, bioavailability, safety, low-cost effectiveness, and immuno-compatibility with the host. In this review, we outlined the anti-cancer properties of Lactoferrin (Lf), an iron-binding glycoprotein of the innate immune defense. Lf shows high bioavailability after oral administration, high selectivity toward cancer cells, and a wide range of molecular targets controlling tumor proliferation, survival, migration, invasion, and metastasization. Of note, Lf is able to promote or inhibit cell proliferation and migration depending on whether it acts upon normal or cancerous cells, respectively. Importantly, Lf administration is highly tolerated and does not present significant adverse effects. Moreover, Lf can prevent development or inhibit cancer growth by boosting adaptive immune response. Finally, Lf was recently found to be an ideal carrier for chemotherapeutics, even for the treatment of brain tumors due to its ability to cross the blood-brain barrier, thus globally appearing as a promising tool for cancer prevention and treatment, especially in combination therapies

Some new insights in swelling and swelling pressure of low active clay

This paper presents a multidimensional chemo-mechanical model for saturated clay treated as a two-phase deformable and chemically reactive porous medium. The constitutive relation is an extension of the original chemo-mechanical model proposed by Gajo et al. (2002) and Loret et al. (2002), in which a q-p formulation was proposed with a Cam-Clay-like elastic response. A novel hyper-elastic law is proposed in which shear stiffness and bulk stiffness change with stress state and ion concentration in pore solution. The proposed constitutive model and the associated coupled finite element formulation are implemented in a 2D, commercial, finite element code (ABAQUS) in the form of user-defined external subroutines. The proposed framework is used to simulate the oedometer tests performed on a low activity clay extracted from Costa della Gaveta slope. The computed chemo mechanical behaviour of the material prepared with distilled water is compared with the experimental results obtained from reconstituted specimens. Moreover, swelling and swelling pressure are computed for the overconsolidated material reconstituted with 1 M NaCl solution and then exposed to distilled water. The comparison of simulations and experiments shows a good agreement

Analysis of gut microbiota in rheumatoid arthritis patients. Disease-related dysbiosis and modifications induced by etanercept

A certain number of studies were carried out to address the question of how dysbiosis could affect the onset and development of rheumatoid arthritis (RA), but little is known about the reciprocal influence between microbiota composition and immunosuppressive drugs, and how this interaction may have an impact on the clinical outcome. The aim of this study was to characterize the intestinal microbiota in a groups of RA patients treatment-naïve, under methotrexate, and/or etanercept (ETN). Correlations between the gut microbiota composition and validated immunological and clinical parameters of disease activity were also evaluated. In the current study, a 16S analysis was employed to explore the gut microbiota of 42 patients affected by RA and 10 healthy controls. Disease activity score on 28 joints (DAS-28), erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, anti-cyclic citrullinated peptides, and dietary and smoking habits were assessed. The composition of the gut microbiota in RA patients free of therapy is characterized by several abnormalities compared to healthy controls. Gut dysbiosis in RA patients is associated with different serological and clinical parameters; in particular, the phylum of Euryarchaeota was directly correlated to DAS and emerged as an independent risk factor. Patients under treatment with ETN present a partial restoration of a beneficial microbiota. The results of our study confirm that gut dysbiosis is a hallmark of the disease, and shows, for the first time, that the anti-tumor necrosis factor alpha (TNF-α) ETN is able to modify microbial communities, at least partially restoring a beneficial microbiota

VOF Simulation of The Cavitating Flow in High Pressure GDI Injectors

The paper describes the development in the OpenFOAM ® technology of a dynamic multiphase Volume-of-Fluid (VoF) solver, supporting mesh handling with topological changes, that has been used for the study of the physics of the primary jet breakup and of the flow disturbance induced by the nozzle geometry during the injector opening event in high-pressure Gasoline Direct Injection (GDI) engines. Turbulence modeling based on a scale-resolving approach has been applied, while phase change of fuel is accounted by means of a cavitation model that has been coupled with the VOF solver. Simulations have been carried out on a 6-hole prototype injector, especially developed for investigations in the framework of the collaborative project FUI MAGIE and provided by Continental Automotive SAS. Special attention has been paid to the domain decomposition strategy and to the code development of the solver, to ensure good load balancing and to minimize inter-processor communication, to achieve good performance and also high scalability on large computing clusters

Syn-exhumation coupling of oceanic and continental units along the western edge of the alpine corsica: A review

The Alpine Corsica represents a segment of the Alpine collisional belt. In its western edge, it is characterized by the close association of continental units deformed under high-pressure metamorphic conditions (Lower Units) and oceanic units showing a metamorphism ranging from high-pressure (Schistes Lus-trés Complex) to very low-grade conditions (Upper Units). This paper provides a complete review of the relationships between the continental and oceanic units in selected five areas where the stratigraphic features, deformation history, metamorphic P-T path and tectonic setting are available for each unit. The collected data indicate that the oceanic units occur not only at the top of the continental ones, as generally proposed in the literature, but also intercalated within them. Such relationships were achieved at shallow structural level during the late stage of exhumation, when the continental units were tectonically coupled with the oceanic units which were dragged as slices from the orogenic wedge. The coupling probably occurred immediately before the transition from syn-to post-orogenic geodynamic regime that affected the whole Alpine-Apennine collisional system in the early Oligocene. After the coupling, the stack of oceanic and continental units experienced a further exhumation-related deformation before their final exposure at the surface

Resonant electron heating and molecular phonon cooling in single C60_{60} junctions

We study heating and heat dissipation of a single \c60 molecule in the junction of a scanning tunneling microscope (STM) by measuring the electron current required to thermally decompose the fullerene cage. The power for decomposition varies with electron energy and reflects the molecular resonance structure. When the STM tip contacts the fullerene the molecule can sustain much larger currents. Transport simulations explain these effects by molecular heating due to resonant electron-phonon coupling and molecular cooling by vibrational decay into the tip upon contact formation.Comment: Accepted in Phys. Rev. Let

The Missing Matter Problem: From the Dark Matter Search to Alternative Hypotheses

Dark matter is among the most important open problems in both astrophysics and particle physics. We review the status of art of dark matter search at theoretical and experimental level discussing also alternative hypotheses