Non-Abelian symmetries and disorder: a broad non-ergodic regime and anomalous thermalization

Symmetries play a central role in single-particle localization. Recent research focused on many-body localized (MBL) systems, characterized by new kind of integrability, and by the area-law entanglement of eigenstates. We investigate the effect of a non-Abelian $SU(2)$ symmetry on the dynamical properties of a disordered Heisenberg chain. While $SU(2)$ symmetry is inconsistent with the conventional MBL, a new non-ergodic regime is possible. In this regime, the eigenstates exhibit faster than area-law, but still a strongly sub-thermal scaling of entanglement entropy. Using exact diagonalization, we establish that this non-ergodic regime is indeed realized in the strongly disordered Heisenberg chains. We use real-space renormalization group (RSRG) to construct approximate excited eigenstates, and show their accuracy for systems of size up to $L=26$. As disorder strength is decreased, a crossover to the thermalizing phase occurs. To establish the ultimate fate of the non-ergodic regime in the thermodynamic limit, we develop a novel approach for describing many-body processes that are usually neglected by RSRG, accessing systems of size $L>2000$. We characterize the resonances that arise due to such processes, finding that they involve an ever growing number of spins as the system size is increased. The probability of finding resonances grows with the system size. Even at strong disorder, we can identify a large lengthscale beyond which resonances proliferate. Presumably, this eventually would drive the system to a thermalizing phase. However, the extremely long thermalization time scales indicate that a broad non-ergodic regime will be observable experimentally. Our study demonstrates that symmetries control dynamical properties of disordered, many-body systems. The approach introduced here provides a versatile tool for describing a broad range of disordered many-body systems.Comment: 25 pages, 21 figure

CALCIUM HANDLING IN MYOGENIC PROGENITORS AND SKELETAL MYOBLASTS: THE ROLE OF CD20

The calcium ion plays an essential role in the physiology of all living cells. Accordingly, multiple mechanisms contribute to the precise control of its intracellular concentration ([Ca2+]i). Particularly in skeletal muscle, the efficient regulation of cytosolic Ca2+ is crucial for tissue functionality and impairment of Ca2+ homeostasis has been shown to contribute to the etiology of muscular disorders such as Duchenne muscular dystrophy (DMD). Although the impairment of Ca2+ homeostasis affecting dystrophic muscular cells has been extensively reported, the pathways involved in calcium-release and the role of store-operated Ca2+ channels in dystrophic myogenic progenitors were not investigated before. Among the heterogeneous population of circulating hematopoietic and endothelial progenitors, we identified a subpopulation of CD133+ cells displaying myogenic properties. Interestingly, expression of the B-cell marker CD20 was observed in blood-derived CD133+ stem cells. Among the scarce available data about the biological role of the membrane protein CD20, there are some evidences of its involvement in the regulation of intracellular calcium concentration ([Ca2+]i). Here, we show that a CD20-related pathway leading to an increase of cytosolic calcium is differently activated in normal and dystrophic blood-derived CD133+ stem cells, supporting the assumption of a CD20-related calcium impairment affecting dystrophic cells. Although CD20 can modulate cytosolic calcium through a specific signaling pathway, other studies demonstrated its association with lipid raft domains of the plasma membrane, where it probably functions directly as a store-operated Ca2+ channel. Recent works indicated that store-operated Ca2+ entry (SOCE) plays a central role in skeletal muscle physiology and development, but there remain a number of unresolved issues relating to SOCE modulation in this tissue. That being so, and considering that blood and muscle share common mesodermic origins, we were prompted to investigate whether CD20 contributes to calcium handling in committed muscular cells. Expression of CD20 was observed in skeletal muscle, displaying a membrane localization in myoblasts and adult muscle fibers. Additionally, we showed that inhibition of CD20 resulted in specific impairment of SOCE in C2C12 myoblasts. Together, reported findings contributed to identify deregulated pathways affecting dystrophic stem cells and potentially involved in DMD pathology. Moreover, our results suggested that functional CD20 is required for SOCE to consistently occur in C2C12 myoblasts, providing a novel insight to improve the understanding of store-operated Ca2+ entry regulation in skeletal muscle

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

Perinatal variation and covariation of oxidative status and telomere length in yellow-legged gull chicks.

The perinatal period is critical to survival and performance of many organisms. In birds, rapid postnatal growth and sudden exposure to aerial oxygen around hatching markedly affect the chick redox status, with potentially negative consequences on physiology mediated by oxidative stress. In addition, telomere length (TL) undergoes reduction during birds' early life, partly depending on oxidative status. However, relatively few studies have focused specifically on the changes in oxidative status and TL that occur immediately after hatching. In this study of the yellow-legged gull Larus michahellis, we found that chicks undergo a marked increase in plasma total antioxidant capacity and a marked decrease in the concentration of pro-oxidant molecules during the first days after hatching. In addition, TL in erythrocytes decreased by 1 standard deviation over the 4 days post-hatching. Body mass and tarsus length covaried with total antioxidant capacity and concentration of pro-oxidants in a complex way, that partly depended on sex and laying order, suggesting that oxidative status can affect growth. Moreover, TL positively covaried with the concentration of pro-oxidant molecules, possibly because retention of high concentrations of pro-oxidant molecules results from mechanisms of prevention of their negative effects, including reduction in TL. Thus, this study shows that chicks undergo marked variation in oxidative status, which predicts growth and subsequent TL, prompting for more studies of the perinatal changes in the critical post-hatching stages

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