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

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

Gravitational effects on a rigid Casimir cavity

Vacuum fluctuations produce a force acting on a rigid Casimir cavity in a weak gravitational field. Such a force is here evaluated and is found to have opposite direction with respect to the gravitational acceleration; the order of magnitude for a multi-layer cavity configuration is analyzed and experimental detection is discussed, bearing in mind the current technological resources.Comment: 7 pages, Latex. Talk given at the Fifth Leipzig Workshop on Quantum Field Theory under the Influence of External Conditions, September 200

The root towards more circularized animal production systems: From animal to territorial metabolism

This paper deals with a relevant topic in the literature on sustainable management of animal farms, concerning the transition towards circular methods of animal production. The paper aims to put forward an original analytical multilevel perspective overlapping different dimensions at either micro, meso, and macro level. Starting from the Malthusian analysis on depletion of natural resources, with risks of the fragility of the natural and economic systems, the paper points out the importance of moving away from intensive methods of production, by adopting more circularized approaches based on resources efficiency. The application of circular economy approaches to animal production is theorized through the concept of territorial metabolism involving not only internal resources (at the animal farm level) but also territorial resources. The paper underlines the critical points of the transition, which is labeled as a socio-technical transition in that it involves not only technical issues but also social aspects. Critical points are addressed through consumers\u2019 acceptance of products drawn on circular approaches and political support to transition, through political tools which are boosted in recent documents of the European Union, like the Green Deal and Farm to Fork strategy

The root towards more circularized animal production systems: From animal to territorial metabolism

This paper deals with a relevant topic in the literature on sustainable management of animal farms, concerning the transition towards circular methods of animal production. The paper aims to put forward an original analytical multilevel perspective overlapping different dimensions at either micro, meso, and macro level. Starting from the Malthusian analysis on depletion of natural resources, with risks of the fragility of the natural and economic systems, the paper points out the importance of moving away from intensive methods of production, by adopting more circularized approaches based on resources efficiency. The application of circular economy approaches to animal production is theorized through the concept of territorial metabolism involving not only internal resources (at the animal farm level) but also territorial resources. The paper underlines the critical points of the transition, which is labeled as a socio-technical transition in that it involves not only technical issues but also social aspects. Critical points are addressed through consumers’ acceptance of products drawn on circular approaches and political support to transition, through political tools which are boosted in recent documents of the European Union, like the Green Deal and Farm to Fork strategy

Modulation of macrophage activation by prostaglandins

The effect of prostaglandtn E2, iloprost and cAMP on both nitric oxide and tumour necrosis factor-α release in J774 macrophages has been studied. Both prostaglandin E2 and iloprost inhibited, in a concentration-dependent fashion, the lipopolysaccharide-induced generation of nitric oxide and tumour necrosis factor-α. The inhibitory effect of these prostanoids seems to be mediated by an increase of the second messenger cAMP since it was mimicked by dibutyryl cAMP and potentiated by the selective type IV phosphodiesterase inhibitor RO-20-1724. Our results suggest that the inhibition of nitric oxide release by prostaglandin E2 and iloprost in lipopolysaccharide-activated J774 macrophages may be secondary to the inhibition of tumour necrosis factor-α generation, which in turn is likely to be mediated by cAMP

The inhibition by hydrocortisone of prostaglandin biosynthesis in rat peritoneal leucocytes is correlated with intracellular macrocortin levels

Hydrocortisone inhibits prostaglandin generation by rat peritoneal leucocytes by releasing the polypeptide phospholipase inhibitor, macrocortin. The susceptibility of these cells to hydrocortisone is directly correlated with their intracellular macrocortin content. Cells depleted of the peptide by prior incubation with steroid cannot respond to the steroid, until a fresh intracellular store has been synthesized. In vitro, this process requires 4-5 h. Cells remain sensitive to the inhibitory action of the peptide at all times

New insights into Chlamydiae persistence: an energy metabolism strategy?

Chlamydiaceae is a family of obligate intracellular bacteria generally considered energy parasites. Several studies have suggested that Chlamydiae are capable of independently producing energy and, more importantly, several genes involved in the energy metabolism are up-regulated during the persistent state. Thus, it has been suggested that chlamydial persistence could be a complex and flexible metabolic strategy designed to favor a lengthy survival in the host cell by evading the immune response. In conclusion, more detailed studies on the shift in the chlamydial energy metabolism, from the active to the persistent form, may be helpful in future to determine whether chlamydial persistence observed in vitro does occur in vivo and whether chronic sequelae of chlamydial diseases may be related to the persistence

Long-term treatment with high-dose of sildenafil in a thalassemic patient with pulmonary hypertension

We report a case of a 37-years-old man, affected by thalassemia major, hypogonadotropic hypogonadism, chronic HCV-hepatitis, diabetes mellitus, severe osteoporosis, prior septic pulmonary embolism and pulmonary artery hypertension was performed a long-term treatment with highdose of sildenafil (120 mg/die) with reduction of pulmonary arterial systolic pressure and of the dyspnea